Obesity and oxidative stress: Implications for female fertility

Abstract

Obesity has reached epidemic proportions in most parts of the world, and it is estimated that 1 billion people globally are trapped in an obesity pandemic, which has seriously compromised human health. Recently, there has been a flood of research into obesity as well as redox and lipid metabolism; however, our understanding of the pathways and specific molecular mechanisms by which obesity-induced oxidative stress affects female reproductive function remains limited. In this review, we discuss how the obesity pandemic has led to lower female fertility. We focus on multiple facets of obesity-mediated reproductive dysfunction, including follicular atresia, oocyte maturation, embryo implantation, reproductive aging, and discuss therapeutic interventions that have the potential to normalize reproductive function in obese females, such as targeting mitochondrial lipid metabolism and antioxidant pathways.

Keywords

antioxidant strategies / female infertility / mitochondria lipid metabolism / obesity / oocyte maturation / oxidative stress

References

[1] Frank, J. (2016). Origins of the obesity pandemic can be analysed. Nature, 532(7598), 149.

[2] Popov, V. B., Aytaman, A., & Aleman, J. O. (2022). Obesity: The forgotten pandemic. American Journal of Gastroenterology, 117(1), 7–10.

[3] Bluher, M. (2019). Obesity: Global epidemiology and pathogenesis. Nature Reviews Endocrinology, 15(5), 288–298.

[4] Cobiac, L. J., & Scarborough, P. (2021). Modelling future trajectories of obesity and body mass index in England. PLoS One, 16(6), e0252072.

[5] Santos, A. L., & Sinha, S. (2021). Obesity and aging: Molecular mechanisms and therapeutic approaches. Ageing Research Reviews, 67, 101268.

[6] Yao, J., Wu, D., & Qiu, Y. (2022). Adipose tissue macrophage in obesity-associated metabolic diseases. Frontiers in Immunology, 13, 977485.

[7] Piche, M. E., Tchernof, A., & Despres, J. P. (2020). Obesity phenotypes, diabetes, and cardiovascular diseases. Circulation Research, 126(11), 1477–1500.

[8] Penzias, A., Azziz, R., Bendikson, K., Falcone, T., Hansen, K., Hill, M., Jindal, S., Kalra, S., Mersereau, J., Reindollar, R., Shannon, C. N., Steiner, A., Tanrikut, C., Taylor, H., & Yauger, B. (2021). Obesity and reproduction: A committee opinion. Fertility and Sterility, 116(5), 1266–1285.

[9] Lima, J., Moreira, N. C. S., & Sakamoto-Hojo, E. T. (2022). Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia. Mutation Research: Genetic Toxicology and Environmental Mutagenesis, 874–875, 503437.

[10] Leisegang, K., Sengupta, P., Agarwal, A., & Henkel, R. (2021). Obesity and male infertility: Mechanisms and management. Andrologia, 53(1), e13617.

[11] Gambineri, A., Laudisio, D., Marocco, C., Radellini, S., Colao, A., & Savastano, S. (2019). Female infertility: Which role for obesity? International Journal of Obesity Supplements, 9(1), 65–72.

[12] Hazelwood, E., Sanderson, E., Tan, V. Y., Ruth, K. S., Frayling, T. M., Dimou, N., Gunter, M. J., Dossus, L., Newton, C., Ryan, N., Pournaras, D. J., O’Mara, T. A., Davey Smith, G., Martin, R. M., & Yarmolinsky, J. (2022). Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: A Mendelian randomization analysis. BMC Medicine, 20(1), 125.

[13] Cena, H., Chiovato, L., & Nappi, R. E. (2020). Obesity, polycystic ovary syndrome, and infertility: A new avenue for GLP-1 receptor agonists. Journal of Clinical Endocrinology & Metabolism, 105(8), e2695–e2709.

[14] Harper, L. M., Jauk, V., Longo, S., Biggio, J. R., Szychowski, J. M., & Tita, A. T. (2020). Early gestational diabetes screening in obese women: A randomized controlled trial. American Journal of Obstetrics and Gynecology, 222(5), 495.e491–495.e498.

[15] Incedal Irgat, S., & Bakirhan, H. (2022). The effect of obesity on human reproductive health and foetal life. Human Fertility, 25(5), 860–871.

[16] Shcherbakova, E. M. (2022). Population dynamics in Russia in the context of global trends. Studies on Russian Economic Development, 33(4), 409–421.

[17] Vollset, S. E., Goren, E., Yuan, C. W., Cao, J., Smith, A. E., Hsiao, T., Bisignano, C., Azhar, G. S., Castro, E., Chalek, J., Dolgert, A. J., Frank, T., Fukutaki, K., Hay, S. I., Lozano, R., Mokdad, A. H., Nandakumar, V., Pierce, M., Pletcher, M., , & Murray, C. J. L. (2020). Fertility, mortality, migration, and population scenarios for 195 countries and territories from 2017 to 2100: A forecasting analysis for the Global Burden of Disease Study. Lancet, 396(10258), 1285–1306.

[18] Schetz, M., De Jong, A., Deane, A. M., Druml, W., Hemelaar, P., Pelosi, P., Pickkers, P., Reintam-Blaser, A., Roberts, J., Sakr, Y., & Jaber, S. (2019). Obesity in the critically ill: A narrative review. Intensive Care Medicine, 45(6), 757–769.

[19] Mohammed, M. S., Sendra, S., Lloret, J., & Bosch, I. (2018). Systems and WBANs for controlling obesity. Journal of Healthcare Engineering, 2018, 1564748.

[20] Ringel, A. E., Drijvers, J. M., Baker, G. J., Catozzi, A., García-Cañaveras, J. C., Gassaway, B. M., Miller, B. C., Juneja, V. R., Nguyen, T. H., Joshi, S., Yao, C. H., Yoon, H., Sage, P. T., LaFleur, M. W., Trombley, J. D., Jacobson, C. A., Maliga, Z., Gygi, S. P., Sorger, P. K., & Haigis, M. C. (2020). Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell, 183(7), 1848–1866.e1826.

[21] Choromanska, B., Myśliwiec, P., Dadan, J., Maleckas, A., Zalewska, A., & Maciejczyk, M. (2021). Effects of age and gender on the redox homeostasis of morbidly obese people. Free Radical Biology and Medicine, 175, 108–120.

[22] Silvestris, E., de Pergola, G., Rosania, R., & Loverro, G. (2018). Obesity as disruptor of the female fertility. Reproductive Biology and Endocrinology, 16(1), 22.

[23] Tripathi, A., Fanning, S., & Dettmer, U. (2021). Lipotoxicity downstream of alpha-synuclein imbalance: A relevant pathomechanism in synucleinopathies? Biomolecules, 12(1), 40.

[24] Soares de Oliveira, A. R., Jayanne Clímaco Cruz, K., Beatriz Silva Morais, J., Rocha Dos Santos, L., Rodrigues de Sousa Melo, S., Fontenelle, L. C., Santos de Sousa, G., Costa Maia, C. S., Oliveira Duarte de Araújo, C., Leal Mendes, I., Simeone Henriques, G., Costa Silva, V., & do Nascimento Marreiro, D. (2021). Selenium status and oxidative stress in obese: Influence of adiposity. European Journal of Clinical Investigation, 51(9), e13538.

[25] Xu, S., Li, S., Bjorklund, M., & Xu, S. (2022). Mitochondrial fragmentation and ROS signaling in wound response and repair. Cell Regeneration, 11(1), 38.

[26] Jia, L., Ma, T., Lv, L., Yu, Y., Zhao, M., Chen, H., & Gao, L. (2023). Endoplasmic reticulum stress mediated by ROS participates in cadmium exposure-induced MC3T3-E1 cell apoptosis. Ecotoxicology and Environmental Safety, 251, 114517.

[27] Leem, J., Kim, S., Kim, J. S., & Oh, J. S. (2022). ROS-independent cytotoxicity of 9,10-phenanthrenequinone inhibits cell cycle progression and spindle assembly during meiotic maturation in mouse oocytes. Journal of Hazardous Materials, 436, 129248.

[28] Ying, W., Gao, H., Dos Reis, F. C. G., Bandyopadhyay, G., Ofrecio, J. M., Luo, Z., Ji, Y., Jin, Z., Ly, C., & Olefsky, J. M. (2021). MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice. Cell Metabolism, 33(4), 781–790.e785.

[29] Chen, X., Xiao, Z., Cai, Y., Huang, L., & Chen, C. (2022). Hypothalamic mechanisms of obesity-associated disturbance of hypothalamic-pituitary-ovarian axis. Trends in Endocrinology and Metabolism, 33(3), 206–217.

[30] Smits, A., Marei, W. F. A., De Neubourg, D., & Leroy, J. (2021). Diet normalization or caloric restriction as a preconception care strategy to improve metabolic health and oocyte quality in obese outbred mice. Reproductive Biology and Endocrinology, 19(1), 166.

[31] Wen, X., Han, Z., Liu, S. J., Hao, X., Zhang, X. J., Wang, X. Y., Zhou, C. J., Ma, Y. Z., & Liang, C. G. (2020). Phycocyanin improves reproductive ability in obese female mice by restoring ovary and oocyte quality. Frontiers in Cell and Developmental Biology, 8, 595373.

[32] Aronne, L. J., Nelinson, D. S., & Lillo, J. L. (2009). Obesity as a disease state: A new paradigm for diagnosis and treatment. Clinical Cornerstone, 9(4), 9–25; discussion 26–29.

[33] Littleton, S. H., Berkowitz, R. I., & Grant, S. F. A. (2020). Genetic determinants of childhood obesity. Molecular Diagnosis and Therapy, 24(6), 653–663.

[34] Yeomans, M. R., & Gray, R. W. (2002). Opioid peptides and the control of human ingestive behaviour. Neuroscience & Biobehavioral Reviews, 26(6), 713–728.

[35] Widdowson, P. S., & Holman, R. B. (1992). Ethanol-induced increase in endogenous dopamine release may involve endogenous opiates. Journal of Neurochemistry, 59(1), 157–163.

[36] Yeomans, M. R., Caton, S., & Hetherington, M. M. (2003). Alcohol and food intake. Current Opinion in Clinical Nutrition and Metabolic Care, 6, 639–644.

[37] Parascandola, M., & Xiao, L. (2019). Tobacco and the lung cancer epidemic in China. Translational Lung Cancer Research, 8(S1), S21–S30.

[38] Svendsen, M., Heggen, E., Klemsdal, T. O., & Tonstad, S. (2021). Diet, eating behaviour and weight gain in men and women with overweight/obesity receiving varenicline for smoking cessation. Clinical Obesity, 11(3), e12447.

[39] Bischoff, S. C., Boirie, Y., Cederholm, T., Chourdakis, M., Cuerda, C., Delzenne, N. M., Deutz, N. E., Fouque, D., Genton, L., Gil, C., Koletzko, B., Leon-Sanz, M., Shamir, R., Singer, J., Singer, P., Stroebele-Benschop, N., Thorell, A., Weimann, A., & Barazzoni, R. (2017). Towards a multidisciplinary approach to understand and manage obesity and related diseases. Clinical Nutrition, 36(4), 917–938.

[40] Cheng, H., Montgomery, S., Green, A., & Furnham, A. (2020). Biomedical, psychological, environmental and behavioural factors associated with adult obesity in a nationally representative sample. Journal of Public Health, 42(3), 570–578.

[41] Cao, C., Friedenreich, C. M., & Yang, L. (2022). Association of daily sitting time and leisure-time physical activity with survival among US cancer survivors. JAMA Oncology, 8(3), 395–403.

[42] Roake, J., Phelan, S., Alarcon, N., Keadle, S. K., Rethorst, C. D., & Foster, G. D. (2021). Sitting time, type, and context among long-term weight-loss maintainers. Obesity, 29(6), 1067–1073.

[43] McHill, A. W., Hull, J. T., & Klerman, E. B. (2022). Chronic circadian disruption and sleep restriction influence subjective hunger, appetite, and food preference. Nutrients, 14(9), 1800.

[44] Kuang, Z., Wang, Y., Li, Y., Ye, C., Ruhn, K. A., Behrendt, C. L., Olson, E. N., & Hooper, L. V. (2019). The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science, 365(6460), 1428–1434.

[45] Wang, Y., Kuang, Z., Yu, X., Ruhn, K. A., Kubo, M., & Hooper, L. V. (2017). The intestinal microbiota regulates body composition through NFIL3 and the circadian clock. Science, 357(6354), 912–916.

[46] Sogari, G., Velez-Argumedo, C., Gomez, M. I., & Mora, C. (2018). College students and eating habits: A study using an ecological model for healthy behavior. Nutrients, 10(12), 1823.

[47] D’Innocenzo, S., Biagi, C., & Lanari, M. (2019). Obesity and the Mediterranean diet: A review of evidence of the role and sustainability of the Mediterranean diet. Nutrients, 11(6), 1306.

[48] Lauridsen, C. (2020). Effects of dietary fatty acids on gut health and function of pigs pre- and post-weaning. Journal of Animal Science, 98(4).

[49] Feingold, K. R. (2022). Lipid and lipoprotein metabolism. Endocrinology and Metabolism Clinics of North America, 51(3), 437–458.

[50] Olzmann, J. A., & Carvalho, P. (2019). Dynamics and functions of lipid droplets. Nature Reviews Molecular Cell Biology, 20(3), 137–155.

[51] Yoon, H., Shaw, J. L., Haigis, M. C., & Greka, A. (2021). Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity. Molecular Cell, 81(18), 3708–3730.

[52] Roberts, M. A., & Olzmann, J. A. (2020). Protein quality control and lipid droplet metabolism. Annual Review of Cell and Developmental Biology, 36(1), 115–139.

[53] Zhu, Q., An, Y. A., & Scherer, P. E. (2022). Mitochondrial regulation and white adipose tissue homeostasis. Trends in Cell Biology, 32(4), 351–364.

[54] Ikeda, K., & Yamada, T. (2020). UCP1 dependent and independent thermogenesis in brown and beige adipocytes. Frontiers in Endocrinology, 11, 498.

[55] Yook, J. S., & Kajimura, S. (2022). Is thermogenesis really needed for brown adipose tissue-mediated metabolic benefit? Journal of Clinical Investigation, 132(9).

[56] Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G. A., Beguinot, F., & Miele, C. (2019). Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. International Journal of Molecular Sciences, 20(9), 2358.

[57] Maurer, S., Harms, M., & Boucher, J. (2021). The colorful versatility of adipocytes: White-to-brown transdifferentiation and its therapeutic potential in humans. FEBS Journal, 288(12), 3628–3646.

[58] Koenen, M., Hill, M. A., Cohen, P., & Sowers, J. R. (2021). Obesity, adipose tissue and vascular dysfunction. Circulation Research, 128(7), 951–968.

[59] Wade, G., McGahee, A., Ntambi, J. M., & Simcox, J. (2021). Lipid transport in brown adipocyte thermogenesis. Frontiers in Physiology, 12, 787535.

[60] Reinisch, K. M., & Prinz, W. A. (2021). Mechanisms of nonvesicular lipid transport. The Journal of Cell Biology, 220(3).

[61] Jia, Z., Pei, Z., Maiguel, D., Toomer, C. J., & Watkins, P. A. (2007). The fatty acid transport protein (FATP) family: Very long chain acyl-CoA synthetases or solute carriers? Journal of Molecular Neuroscience, 33(1), 25–31.

[62] Huang, X., Zhou, Y., Sun, Y., & Wang, Q. (2022). Intestinal fatty acid binding protein: A rising therapeutic target in lipid metabolism. Progress in Lipid Research, 87, 101178.

[63] Hao, J. W., Wang, J., Guo, H., Zhao, Y. Y., Sun, H. H., Li, Y. F., Lai, X. Y., Zhao, N., Wang, X., Xie, C., Hong, L., Huang, X., Wang, H. R., Liang, B., Chen, S., & Zhao, T. J. (2020). CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis. Nature Communications, 11(1), 4765.

[64] Ulu, A., & Frost, J. A. (2020). Regulation of RhoA activation and cell motility by c-Jun N-terminal kinases and Net1. Small GTPases, 11(6), 385–391.

[65] Papagiannouli, F. (2022). Endocytosis at the crossroad of polarity and signaling regulation: Learning from Drosophila melanogaster and beyond. International Journal of Molecular Sciences, 23(9), 4684.

[66] Rahaman, S. O., Swat, W., Febbraio, M., & Silverstein, R. L. (2011). Vav family Rho guanine nucleotide exchange factors regulate CD36-mediated macrophage foam cell formation. Journal of Biological Chemistry, 286(9), 7010–7017.

[67] Samovski, D., Jacome-Sosa, M., & Abumrad, N. A. (2023). Fatty acid transport and signaling: Mechanisms and physiological implications. Annual Review of Physiology, 85(1), 317–337.

[68] Moore, M. P., Cunningham, R. P., Meers, G. M., Johnson, S. A., Wheeler, A. A., Ganga, R. R., Spencer, N. M., Pitt, J. B., Diaz-Arias, A., Swi, A. I. A., Hammoud, G. M., Ibdah, J. A., Parks, E. J., & Rector, R. S. (2022). Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD. Hepatology, 76(5), 1452–1465.

[69] Timper, K., del Río-Martín, A., Cremer, A. L., Bremser, S., Alber, J., Giavalisco, P., Varela, L., Heilinger, C., Nolte, H., Trifunovic, A., Horvath, T. L., Kloppenburg, P., Backes, H., & Brüning, J. C. (2020). GLP-1 receptor signaling in astrocytes regulates fatty acid oxidation, mitochondrial integrity, and function. Cell Metabolism, 31(6), 1189–1205.e1113.

[70] Yang, H., Deng, Q., Ni, T., liu, Y., Lu, L., Dai, H., Wang, H., & Yang, W. (2021). Targeted inhibition of LPL/FABP4/CPT1 fatty acid metabolic axis can effectively prevent the progression of nonalcoholic steatohepatitis to liver cancer. International Journal of Biological Sciences, 17(15), 4207–4222.

[71] Talenezhad, N., Mohammadi, M., Ramezani-Jolfaie, N., Mozaffari-Khosravi, H., & Salehi-Abargouei, A. (2020). Effects of l-carnitine supplementation on weight loss and body composition: A systematic review and meta-analysis of 37 randomized controlled clinical trials with dose-response analysis. Clinical Nutrition ESPEN, 37, 9–23.

[72] Chen, J., Zou, L., Grinchuk, O., Fang, L., Ong, D. S. T., Taneja, R., Ong, C. N., & Shen, H. M. (2022). PFKP alleviates glucose starvation-induced metabolic stress in lung cancer cells via AMPK-ACC2 dependent fatty acid oxidation. Cell Discovery, 8(1), 52.

[73] Liu, H. X., Zhao, H., Xi, C., Ma, L. P., Lu, X., Yan, J., Tian, X. L., Gao, L., Tian, M., & Liu, Q. J. (2022). CPT1 mediated ionizing radiation-induced intestinal injury proliferation via shifting FAO metabolism pathway and activating the ERK1/2 and JNK pathway. Radiation Research, 198(5), 488–507.

[74] Agrawal, V., Hemnes, A. R., Shelburne, N. J., Fortune, N., Fuentes, J. L., Colvin, D., Calcutt, M. W., Talati, M., Poovey, E., West, J. D., & Brittain, E. L. (2022). l-Carnitine therapy improves right heart dysfunction through Cpt1-dependent fatty acid oxidation. Pulmonary Circulation, 12(3), e12107.

[75] Houten, S. M., Wanders, R. J. A., & Ranea-Robles, P. (2020). Metabolic interactions between peroxisomes and mitochondria with a special focus on acylcarnitine metabolism. Biochimica et Biophysica Acta, Molecular Basis of Disease, 1866(5), 165720.

[76] Misheva, M., Kotzamanis, K., Davies, L. C., Tyrrell, V. J., Rodrigues, P. R. S., Benavides, G. A., Hinz, C., Murphy, R. C., Kennedy, P., Taylor, P. R., Rosas, M., Jones, S. A., McLaren, J. E., Deshpande, S., Andrews, R., Schebb, N. H., Czubala, M. A., Gurney, M., Aldrovandi, M., & O’Donnell, V. B. (2022). Oxylipin metabolism is controlled by mitochondrial beta-oxidation during bacterial inflammation. Nature Communications, 13(1), 139.

[77] Wang, Y., Yu, W., Li, S., Guo, D., & He, J. (2022). Acetyl-CoA carboxylases and diseases. Frontiers in Oncology, 12, 836058.

[78] Yang, J. H., Kim, N. H., Yun, J. S., Cho, E. S., Cha, Y. H., Cho, S. B., Lee, S. H., Cha, S. Y., Kim, S. Y., Choi, J., Nguyen, T. T. M., Park, S., Kim, H. S., & Yook, J. I. (2020). Snail augments fatty acid oxidation by suppression of mitochondrial ACC2 during cancer progression. Life Science Alliance, 3(7), e202000683.

[79] Bettendorff, L. (2022). Reduced nucleotides, thiols and O(2) in cellular redox balance: A biochemist’s view. Antioxidants, 11(10), 1877.

[80] Arnold, P. K., Jackson, B. T., Paras, K. I., Brunner, J. S., Hart, M. L., Newsom, O. J., Alibeckoff, S. P., Endress, J., Drill, E., Sullivan, L. B., & Finley, L. W. S. (2022). A non-canonical tricarboxylic acid cycle underlies cellular identity. Nature, 603(7901), 477–481.

[81] Vercellino, I., & Sazanov, L. A. (2022). The assembly, regulation and function of the mitochondrial respiratory chain. Nature Reviews Molecular Cell Biology, 23(2), 141–161.

[82] Shao, D., Kolwicz, S. C., Jr., Wang, P., Roe, N. D., Villet, O., Nishi, K., Hsu, Y. W. A., Flint, G. V., Caudal, A., Wang, W., Regnier, M., & Tian, R. (2020). Increasing fatty acid oxidation prevents high-fat diet-induced cardiomyopathy through regulating parkin-mediated mitophagy. Circulation, 142(10), 983–997.

[83] Zong, Y., Zhang, C. S., Li, M., Wang, W., Wang, Z., Hawley, S. A., Ma, T., Feng, J. W., Tian, X., Qi, Q., Wu, Y. Q., Zhang, C., Ye, Z., Lin, S. Y., Piao, H. L., Hardie, D. G., & Lin, S. C. (2019). Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress. Cell Research, 29(6), 460–473.

[84] Geng, Y., Faber, K. N., de Meijer, V. E., Blokzijl, H., & Moshage, H. (2021). How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease? Hepatology International, 15(1), 21–35.

[85] Hauck, A. K., & Bernlohr, D. A. (2016). Oxidative stress and lipotoxicity. The Journal of Lipid Research, 57(11), 1976–1986.

[86] Jarc, E., & Petan, T. (2019). Lipid droplets and the management of cellular stress. The Yale Journal of Biology and Medicine, 92, 435–452.

[87] Uchida, K. (2003). 4-Hydroxy-2-nonenal: A product and mediator of oxidative stress. Progress in Lipid Research, 42(4), 318–343.

[88] Jarc, E., & Petan, T. (2020). A twist of FATe: Lipid droplets and inflammatory lipid mediators. Biochimie, 169, 69–87.

[89] Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014). Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiological Reviews, 94(3), 909–950.

[90] Ramirez Ortega, D., Ugalde Muñiz, P. E., Blanco Ayala, T., Vázquez Cervantes, G. I., Lugo Huitrón, R., Pineda, B., González Esquivel, D. F., Pérez de la Cruz, G., Pedraza Chaverrí J., Sánchez Chapul, L., Gómez-Manzo, S., & Pérez de la Cruz, V. (2021). On the antioxidant properties of L-kynurenine: An efficient ROS scavenger and enhancer of rat brain antioxidant defense. Antioxidants, 11(1), 31.

[91] Ilari, S., Giancotti, L. A., Lauro, F., Dagostino, C., Gliozzi, M., Malafoglia, V., Sansone, L., Palma, E., Tafani, M., Russo, M. A., Tomino, C., Fini, M., Salvemini, D., Mollace, V., & Muscoli, C. (2020). Antioxidant modulation of sirtuin 3 during acute inflammatory pain: The ROS control. Pharmacological Research, 157, 104851.

[92] Ray, S., Abugable, A. A., Parker, J., Liversidge, K., Palminha, N. M., Liao, C., Acosta-Martin, A. E., Souza, C. D. S., Jurga, M., Sudbery, I., & El-Khamisy, S. F. (2022). A mechanism for oxidative damage repair at gene regulatory elements. Nature, 609(7929), 1038–1047.

[93] Halliwell, B., Adhikary, A., Dingfelder, M., & Dizdaroglu, M. (2021). Hydroxyl radical is a significant player in oxidative DNA damage in vivo. Chemical Society Reviews, 50(15), 8355–8360.

[94] Danieli, M. G., Antonelli, E., Piga, M. A., Cozzi, M. F., Allegra, A., & Gangemi, S. (2023). Oxidative stress, mitochondrial dysfunction, and respiratory chain enzyme defects in inflammatory myopathies. Autoimmunity Reviews, 22(5), 103308.

[95] Broughton, D. E., & Moley, K. H. (2017). Obesity and female infertility: Potential mediators of obesity’s impact. Fertility and Sterility, 107(4), 840–847.

[96] Laforge, M., Elbim, C., Frère, C., Hémadi, M., Massaad, C., Nuss, P., Benoliel, J. J., & Becker, C. (2020). Tissue damage from neutrophil-induced oxidative stress in COVID-19. Nature Reviews Immunology, 20(9), 515–516.

[97] Michel, M., Benítez-Buelga, C., Calvo, P. A., Hanna, B. M. F., Mortusewicz, O., Masuyer, G., Davies, J., Wallner, O., Sanjiv, K., Albers, J. J., Castañeda-Zegarra, S., Jemth, A. S., Visnes, T., Sastre-Perona, A., Danda, A. N., Homan, E. J., Marimuthu, K., Zhenjun, Z., Chi, C. N., & Helleday, T. (2022). Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function. Science, 376(6600), 1471–1476.

[98] Kirichenko, T. V., Markina, Y. V., Bogatyreva, A. I., Tolstik, T. V., Varaeva, Y. R., & Starodubova, A. V. (2022). The role of adipokines in inflammatory mechanisms of obesity. International Journal of Molecular Sciences, 23, 14982.

[99] Zhang, Y., & Chua, S., Jr. (2017). Leptin function and regulation. Comprehensive Physiology, 8, 351–369.

[100] Santa-Maria, C. A., Coughlin, J. W., Sharma, D., Armanios, M., Blackford, A. L., Schreyer, C., Dalcin, A., Carpenter, A., Jerome, G. J., Armstrong, D. K., Chaudhry, M., Cohen, G. I., Connolly, R. M., Fetting, J., Miller, R. S., Smith, K. L., Snyder, C., Wolfe, A., Wolff, A. C., & Stearns, V. (2020). The effects of a remote-based weight loss program on adipocytokines, metabolic markers, and telomere length in breast cancer survivors: The POWER-remote trial. Clinical Cancer Research, 26(12), 3024–3034.

[101] Kawai, T., Autieri, M. V., & Scalia, R. (2021). Adipose tissue inflammation and metabolic dysfunction in obesity. American Journal of Physiology - Cell Physiology, 320(3), C375–C391.

[102] Burn, G. L., Foti, A., Marsman, G., Patel, D. F., & Zychlinsky, A. (2021). The neutrophil. Immunity, 54(7), 1377–1391.

[103] Loh, W., & Vermeren, S. (2022). Anti-inflammatory neutrophil functions in the resolution of inflammation and tissue repair. Cells, 11(24), 4076.

[104] El-Benna, J., Hurtado-Nedelec, M., Gougerot-Pocidalo, M. A., & Dang, P. M. (2021). Effects of venoms on neutrophil respiratory burst: A major inflammatory function. Journal of Venomous Animals and Toxins including Tropical Diseases, 27, e20200179.

[105] McGarry, T., Biniecka, M., Veale, D. J., & Fearon, U. (2018). Hypoxia, oxidative stress and inflammation. Free Radical Biology and Medicine, 125, 15–24.

[106] Zhang, B., Li, X., Liu, G., Zhang, C., Zhang, X., Shen, Q., Sun, G., & Sun, X. (2021). Peroxiredomin-4 ameliorates lipotoxicity-induced oxidative stress and apoptosis in diabetic cardiomyopathy. Biomedicine & Pharmacotherapy, 141, 111780.

[107] Sharma, S., Sharma, P., Bailey, T., Bhattarai, S., Subedi, U., Miller, C., Ara, H., Kidambi, S., Sun, H., Panchatcharam, M., & Miriyala, S. (2022). Electrophilic aldehyde 4-hydroxy-2-nonenal mediated signaling and mitochondrial dysfunction. Biomolecules, 12(11), 1555.

[108] Chen, X., Kang, R., Kroemer, G., & Tang, D. (2021). Broadening horizons: The role of ferroptosis in cancer. Nature Reviews Clinical Oncology, 18(5), 280–296.

[109] Zhou, B., Kreuzer, J., Kumsta, C., Wu, L., Kamer, K. J., Cedillo, L., Zhang, Y., Li, S., Kacergis, M. C., Webster, C. M., Fejes-Toth, G., Naray-Fejes-Toth, A., Das, S., Hansen, M., Haas, W., & Soukas, A. A. (2019). Mitochondrial permeability uncouples elevated autophagy and lifespan extension. Cell, 177(2), 299–314.e216.

[110] Hu, J., Bian, Q., Ma, X., Xu, Y., & Gao, J. (2022). A double-edged sword: ROS related therapies in the treatment of psoriasis. Asian Journal of Pharmaceutical Sciences, 17(6), 798–816.

[111] Liu, X., & Zhang, Z. (2022). A double-edged sword: Reactive oxygen species (ROS) during the rice blast fungus and host interaction. FEBS Journal, 289(18), 5505–5515.

[112] Wang, L., Tang, J., Tan, F., Song, H., Zhou, J., & Li, F. (2021). Oxidative stress in oocyte aging and female reproduction. Journal of Cellular Physiology, 236(12), 7966–7983.

[113] Genchi, G., Sinicropi, M. S., Lauria, G., Carocci, A., & Catalano, A. (2020). The effects of cadmium toxicity. International Journal of Environmental Research and Public Health, 17(11), 3782.

[114] Kim, J., Gupta, R., Blanco, L. P., Yang, S., Shteinfer-Kuzmine, A., Wang, K., Zhu, J., Yoon, H. E., Wang, X., Kerkhofs, M., Kang, H., Brown, A. L., Park, S. J., Xu, X., Zandee van Rilland, E., Kim, M. K., Cohen, J. I., Kaplan, M. J., Shoshan-Barmatz, V., & Chung, J. H. (2019). VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science, 366(6472), 1531–1536.

[115] Wang, W., Zhu, M., Xu, Z., Li, W., Dong, X., Chen, Y., Lin, B., & Li, M. (2019). Ropivacaine promotes apoptosis of hepatocellular carcinoma cells through damaging mitochondria and activating caspase-3 activity. Biological Research, 52(1), 36.

[116] He, Q., Gu, L., Lin, Q., Ma, Y., Liu, C., Pei, X., Li, P. A., & Yang, Y. (2020). The Immp2l mutation causes ovarian aging through ROS-Wnt/beta-catenin-estrogen pathway: Preventive effect of melatonin. Endocrinology, 161(9).

[117] Zhu, M., Miao, S., Zhou, W., Elnesr, S. S., Dong, X., & Zou, X. (2021). MAPK, AKT/FoxO3a and mTOR pathways are involved in cadmium regulating the cell cycle, proliferation and apoptosis of chicken follicular granulosa cells. Ecotoxicology and Environmental Safety, 214, 112091.

[118] Cajas, Y. N., Cañón-Beltrán, K., Ladrón de Guevara, M., Millán de la Blanca, M. G., Ramos-Ibeas, P., Gutiérrez-Adán, A., Rizos, D., & González, E. M. (2020). Antioxidant nobiletin enhances oocyte maturation and subsequent embryo development and quality. International Journal of Molecular Sciences, 21(15), 5340.

[119] Hussain, T., Murtaza, G., Metwally, E., Kalhoro, D. H., Kalhoro, M. S., Rahu, B. A., Sahito, R. G. A., Yin, Y., Yang, H., Chughtai, M. I., & Tan, B. (2021). The role of oxidative stress and antioxidant balance in pregnancy. Mediators of Inflammation, 2021, 9962860.

[120] Ma, Y., Zheng, L., Wang, Y., Gao, Y., & Xu, Y. (2022). Arachidonic acid in follicular fluid of PCOS induces oxidative stress in a human ovarian granulosa tumor cell line (KGN) and upregulates GDF15 expression as a response. Frontiers in Endocrinology, 13, 865748.

[121] Siddiqui, S., Mateen, S., Ahmad, R., & Moin, S. (2022). A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS). Journal of Assisted Reproduction and Genetics, 39(11), 2439–2473.

[122] Zhang, X., Zhang, D., Li, H., Liu, Z., Yang, Y., Li, J., Tang, L., Tao, J., Liu, H., & Shen, M. (2023). Melatonin-mediated suppression of mtROS-JNK-FOXO1 pathway alleviates hypoxia-induced apoptosis in porcine granulosa cells. Antioxidants, 12(10), 1881.

[123] Huang, J. C., Duan, C. C., Jin, S., Sheng, C. B., Wang, Y. S., Yue, Z. P., & Guo, B. (2022). HB-EGF induces mitochondrial dysfunction via estrogen hypersecretion in granulosa cells dependent on cAMP-PKA-JNK/ERK-Ca(2+)-FOXO1 pathway. International Journal of Biological Sciences, 18(5), 2047–2059.

[124] Robker, R. L., Akison, L. K., Bennett, B. D., Thrupp, P. N., Chura, L. R., Russell, D. L., Lane, M., & Norman, R. J. (2009). Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women. Journal of Clinical Endocrinology & Metabolism, 94(5), 1533–1540.

[125] Fedorcsak, P., Dale, P. O., Storeng, R., Ertzeid, G., Bjercke, S., Oldereid, N., Omland, A. K., Åbyholm, T., & Tanbo, T. (2004). Impact of overweight and underweight on assisted reproduction treatment. Human Reproduction, 19(11), 2523–2528.

[126] Pinborg, A., Gaarslev, C., Hougaard, C., Nyboe Andersen, A., Andersen, P., Boivin, J., & Schmidt, L. (2011). Influence of female bodyweight on IVF outcome: A longitudinal multicentre cohort study of 487 infertile couples. Reproductive BioMedicine Online, 23(4), 490–499.

[127] Machtinger, R., Combelles, C. M. H., Missmer, S. A., Correia, K. F., Fox, J. H., & Racowsky, C. (2012). The association between severe obesity and characteristics of failed fertilized oocytes. Human Reproduction, 27(11), 3198–3207.

[128] Luzzo, K. M., Wang, Q., Purcell, S. H., Chi, M., Jimenez, P. T., Grindler, N., Schedl, T., & Moley, K. H. (2012). High fat diet induced developmental defects in the mouse: Oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One, 7(11), e49217.

[129] Choi, W. J., Banerjee, J., Falcone, T., Bena, J., Agarwal, A., & Sharma, R. K. (2007). Oxidative stress and tumor necrosis factor-alpha-induced alterations in metaphase II mouse oocyte spindle structure. Fertility and Sterility, 88(4), 1220–1231.

[130] Blengini, C. S., & Schindler, K. (2022). Acentriolar spindle assembly in mammalian female meiosis and the consequences of its perturbations on human reproductiondagger. Biology of Reproduction, 106(2), 253–263.

[131] Stadtman, E. R., & Levine, R. L. (2003). Free radical-mediated oxidation of free amino acids and amino acid residues in proteins. Amino Acids, 25(3–4), 207–218.

[132] Mihalas, B. P., De Iuliis, G. N., Redgrove, K. A., McLaughlin, E. A., & Nixon, B. (2017). The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress-mediated deterioration of the ageing oocyte. Scientific Reports, 7(1), 6247.

[133] Uchida, K. (2003). Histidine and lysine as targets of oxidative modification. Amino Acids, 25(3–4), 249–257.

[134] Igosheva, N., Abramov, A. Y., Poston, L., Eckert, J. J., Fleming, T. P., Duchen, M. R., & McConnell, J. (2010). Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PLoS One, 5(4), e10074.

[135] Turner, N., & Robker, R. L. (2015). Developmental programming of obesity and insulin resistance: Does mitochondrial dysfunction in oocytes play a role? Molecular Human Reproduction, 21(1), 23–30.

[136] Boudoures, A. L., Saben, J., Drury, A., Scheaffer, S., Modi, Z., Zhang, W., & Moley, K. H. (2017). Obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy. Developmental Biology, 426(1), 126–138.

[137] Marei, W. F. A., Van den Bosch, L., Pintelon, I., Mohey-Elsaeed, O., Bols, P. E. J., & Leroy, J. L. M. R. (2019). Mitochondria-targeted therapy rescues development and quality of embryos derived from oocytes matured under oxidative stress conditions: A bovine in vitro model. Human Reproduction, 34(10), 1984–1998.

[138] Marei, W. F. A., Smits, A., Mohey-Elsaeed, O., Pintelon, I., Ginneberge, D., Bols, P. E. J., Moerloose, K., & Leroy, J. L. M. R. (2020). Differential effects of high fat diet-induced obesity on oocyte mitochondrial functions in inbred and outbred mice. Scientific Reports, 10(1), 9806.

[139] Iljas, J. D., & Homer, H. A. (2020). Sirt3 is dispensable for oocyte quality and female fertility in lean and obese mice. The FASEB Journal, 34(5), 6641–6653.

[140] Zhao, L., Lu, T., Gao, L., Fu, X., Zhu, S., & Hou, Y. (2017). Enriched endoplasmic reticulum-mitochondria interactions result in mitochondrial dysfunction and apoptosis in oocytes from obese mice. Journal of Animal Science and Biotechnology, 8(1), 62.

[141] Melkov, A., & Abdu, U. (2018). Regulation of long-distance transport of mitochondria along microtubules. Cellular and Molecular Life Sciences, 75(2), 163–176.

[142] Basha, E. H., Eltokhy, A. K. B., Eltantawy, A. F., Heabah, N. A. E., Elshwaikh, S. L., & El-Harty, Y. M. (2022). Linking mitochondrial dynamics and fertility: Promoting fertility by phoenixin through modulation of ovarian expression of GnRH receptor and mitochondrial dynamics proteins DRP-1 and Mfn-2. Pflügers Archiv, 474(10), 1107–1119.

[143] Ruan, X. H., Ma, T., & Fan, Y. (2019). Ablation of TMEM126B protects against heart injury via improving mitochondrial function in high fat diet (HFD)-induced mice. Biochemical and Biophysical Research Communications, 515(4), 636–643.

[144] Gong, F., Gao, L., & Ding, T. (2019). IDH2 protects against nonalcoholic steatohepatitis by alleviating dyslipidemia regulated by oxidative stress. Biochemical and Biophysical Research Communications, 514(3), 593–600.

[145] Liu, W., Li, K., Zheng, M., He, L., & Chen, T. (2022). Genipin attenuates diabetic cognitive impairment by reducing lipid accumulation and promoting mitochondrial fusion via FABP4/Mfn1 signaling in microglia. Antioxidants, 12(1), 74.

[146] Zhang, X., Wu, X. Q., Lu, S., Guo, Y. L., & Ma, X. (2006). Deficit of mitochondria-derived ATP during oxidative stress impairs mouse MII oocyte spindles. Cell Research, 16(10), 841–850.

[147] Hou, Y. J., Zhu, C. C., Duan, X., Liu, H. L., Wang, Q., & Sun, S. C. (2016). Both diet and gene mutation induced obesity affect oocyte quality in mice. Scientific Reports, 6(1), 18858.

[148] Wang, L., Chen, Y., Wei, J., Guo, F., Li, L., Han, Z., Wang, Z., Zhu, H., Zhang, X., Li, Z., & Dai, X. (2022). Administration of nicotinamide mononucleotide improves oocyte quality of obese mice. Cell Proliferation, 55(11), e13303.

[149] Wu, N. N., Bi, Y., Ajoolabady, A., You, F., Sowers, J., Wang, Q., Ceylan, A. F., Zhang, Y., & Ren, J. (2022). Parkin insufficiency accentuates high-fat diet-induced cardiac remodeling and contractile dysfunction through VDAC1-mediated mitochondrial Ca²⁺ overload. JACC. Basic to Translational Science, 7(8), 1066–1067.

[150] Wang, H., Cheng, Q., Li, X., Hu, F., Han, L., Zhang, H., Li, L., Ge, J., Ying, X., Guo, X., & Wang, Q. (2018). Loss of TIGAR induces oxidative stress and meiotic defects in oocytes from obese mice. Molecular & Cellular Proteomics, 17(7), 1354–1364.

[151] Zhou, J., Li, X. Y., Liu, Y. J., Feng, J., Wu, Y., Shen, H. M., & Lu, G. D. (2022). Full-coverage regulations of autophagy by ROS: From induction to maturation. Autophagy, 18(6), 1240–1255.

[152] Yamamoto, T., Takabatake, Y., Takahashi, A., Kimura, T., Namba, T., Matsuda, J., Minami, S., Kaimori, J. y., Matsui, I., Matsusaka, T., Niimura, F., Yanagita, M., & Isaka, Y. (2017). High-fat diet-induced lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in the kidney. Journal of the American Society of Nephrology, 28(5), 1534–1551.

[153] Chen, K., Yuan, R., Geng, S., Zhang, Y., Ran, T., Kowalski, E., Liu, J., & Li, L. (2017). Toll-interacting protein deficiency promotes neurodegeneration via impeding autophagy completion in high-fat diet-fed ApoE(-/-) mouse model. Brain, Behavior, and Immunity, 59, 200–210.

[154] Jin, X., Wang, K., Wang, L., Liu, W., Zhang, C., Qiu, Y., Liu, W., Zhang, H., Zhang, D., Yang, Z., Wu, T., & Li, J. (2022). RAB7 activity is required for the regulation of mitophagy in oocyte meiosis and oocyte quality control during ovarian aging. Autophagy, 18(3), 643–660.

[155] Bucci, C., Thomsen, P., Nicoziani, P., McCarthy, J., & van Deurs, B. (2000). Rab7: A key to lysosome biogenesis. Molecular Biology of the Cell, 11(2), 467–480.

[156] Sciorio, R., Bellaminutti, S., Tramontano, L., & Esteves, S. C. (2022). Impact of obesity on medically assisted reproductive treatments. Zygote, 30(4), 431–439.

[157] Jungheim, E. S., Macones, G. A., Odem, R. R., Patterson, B. W., Lanzendorf, S. E., Ratts, V. S., & Moley, K. H. (2011). Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization. Fertility and Sterility, 95(6), 1970–1974.

[158] Zhang, C. X. W., Candia, A. A., & Sferruzzi-Perri, A. N. (2024). Placental inflammation, oxidative stress, and fetal outcomes in maternal obesity. Trends in Endocrinology and Metabolism, 35(7), 638–647.

[159] Jungheim, E. S., Louden, E. D., Chi, M. M. Y., Frolova, A. I., Riley, J. K., & Moley, K. H. (2011). Preimplantation exposure of mouse embryos to palmitic acid results in fetal growth restriction followed by catch-up growth in the offspring. Biology of Reproduction, 85(4), 678–683.

[160] Wentzel, P., Eriksson, U. J., & Herrera, E. (2019). High-fat diet in pregnant rats and adverse fetal outcome. Upsala Journal of Medical Sciences, 124(2), 125–134.

[161] Huang, C. H., Wang, F. T., & Chan, W. H. (2019). Enniatin B1 exerts embryotoxic effects on mouse blastocysts and induces oxidative stress and immunotoxicity during embryo development. Environmental Toxicology, 34(1), 48–59.

[162] Mansuri, M. L., Sharma, G., Parihar, P., Dube, K. T., Sharma, T., Parihar, A., & Parihar, M. S. (2021). Increased oxidative stress and mitochondrial impairments associated with increased expression of TNF-alpha and caspase-3 in palmitic acid-induced lipotoxicity in myoblasts. Journal of Biochemical and Molecular Toxicology, 35(5), e22744.

[163] Huypens, P., Sass, S., Wu, M., Dyckhoff, D., Tschöp, M., Theis, F., Marschall, S., de Angelis, M. H., & Beckers, J. (2016). Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nature Genetics, 48(5), 497–499.

[164] Wyman, A., Pinto, A. B., Sheridan, R., & Moley, K. H. (2008). One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital malformations and growth retardation in offspring. Endocrinology, 149(2), 466–469.

[165] Valckx, S. D., Arias-Alvarez, M., De Pauw, I., Fievez, V., Vlaeminck, B., Fransen, E., Bols, P. E., & Leroy, J. L. (2014). Fatty acid composition of the follicular fluid of normal weight, overweight and obese women undergoing assisted reproductive treatment: A descriptive cross-sectional study. Reproductive Biology and Endocrinology, 12(1), 13.

[166] Desmet, K. L. J., Marei, W. F. A., Richard, C., Sprangers, K., Beemster, G. T. S., Meysman, P., Laukens, K., Declerck, K., Vanden Berghe, W., Bols, P. E. J., Hue, I., & Leroy, J. L. M. R. (2020). Oocyte maturation under lipotoxic conditions induces carryover transcriptomic and functional alterations during post-hatching development of good-quality blastocysts: Novel insights from a bovine embryo-transfer model. Human Reproduction, 35(2), 293–307.

[167] Wei, W., Zhang, X., Zhou, B., Ge, B., Tian, J., & Chen, J. (2022). Effects of female obesity on conception, pregnancy and the health of offspring. Frontiers in Endocrinology, 13, 949228.

[168] Han, L., Ren, C., Li, L., Li, X., Ge, J., Wang, H., Miao, Y. L., Guo, X., Moley, K. H., Shu, W., & Wang, Q. (2018). Embryonic defects induced by maternal obesity in mice derive from Stella insufficiency in oocytes. Nature Genetics, 50(3), 432–442.

[169] St-Germain, L. E., Castellana, B., Baltayeva, J., & Beristain, A. G. (2020). Maternal obesity and the uterine immune cell landscape: The shaping role of inflammation. International Journal of Molecular Sciences, 21(11), 3776.

[170] Weberling, A., & Zernicka-Goetz, M. (2021). Trophectoderm mechanics direct epiblast shape upon embryo implantation. Cell Reports, 34(3), 108655.

[171] Metwally, M., Cutting, R., Tipton, A., Skull, J., & Ledger, W. (2007). Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reproductive BioMedicine Online, 15(5), 532–538.

[172] Schoots, M. H., Gordijn, S. J., Scherjon, S. A., van Goor, H., & Hillebrands, J. L. (2018). Oxidative stress in placental pathology. Placenta, 69, 153–161.

[173] Luo, Z., Xu, X., Sho, T., Zhang, J., Xu, W., Yao, J., & Xu, J. (2019). ROS-induced autophagy regulates porcine trophectoderm cell apoptosis, proliferation, and differentiation. American Journal of Physiology - Cell Physiology, 316(2), C198–C209.

[174] Hill, M. J., Uyehara, C. F., Hashiro, G. M., & Frattarelli, J. L. (2007). The utility of serum leptin and follicular fluid leptin, estradiol, and progesterone levels during an in vitro fertilization cycle. Journal of Assisted Reproduction and Genetics, 24(5), 183–188.

[175] Rhee, J. S., Saben, J. L., Mayer, A. L., Schulte, M. B., Asghar, Z., Stephens, C., Chi, M. M. Y., & Moley, K. H. (2016). Diet-induced obesity impairs endometrial stromal cell decidualization: A potential role for impaired autophagy. Human Reproduction, 31(6), 1315–1326.

[176] Di Angelantonio, E., Bhupathiraju, S. N., Wormser, D., Gao, P., Kaptoge, S., de Gonzalez, A. B., Cairns, B. J., Huxley, R., Jackson, C. L., Joshy, G., Lewington, S., Manson, J. E., Murphy, N., Patel, A. V., Samet, J. M., Woodward, M., Zheng, W., Zhou, M., Bansal, N., & Hu, F. B. (2016). Body-mass index and all-cause mortality: Individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet, 388(10046), 776–786.

[177] Valdes, A. M., Andrew, T., Gardner, J., Kimura, M., Oelsner, E., Cherkas, L., Aviv, A., & Spector, T. (2005). Obesity, cigarette smoking, and telomere length in women. Lancet, 366(9486), 662–664.

[178] Tam, B. T., Morais, J. A., & Santosa, S. (2020). Obesity and ageing: Two sides of the same coin. Obesity Reviews, 21(4), e12991.

[179] Quaye, E., Galecki, A. T., Tilton, N., Whitney, R., Briceño, E. M., Elkind, M. S., Fitzpatrick, A. L., Gottesman, R. F., Griswold, M., Gross, A. L., Heckbert, S. R., Hughes, T. M., Longstreth, W., Jr., Sacco, R. L., Sidney, S., Windham, B. G., Yaffe, K., & Levine, D. A. (2023). Association of obesity with cognitive decline in Black and White Americans. Neurology, 100(2), e220–e231.

[180] Gruber, T., Pan, C., Contreras, R. E., Wiedemann, T., Morgan, D. A., Skowronski, A. A., Lefort, S., De Bernardis Murat, C., Le Thuc, O., Legutko, B., Ruiz-Ojeda, F. J., Fuente-Fernández, M. D. L., García-Villalón, A. L., González-Hedström, D., Huber, M., Szigeti-Buck, K., Müller, T. D., Ussar, S., Pfluger, P., & García-Cáceres, C. (2021). Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension. Cell Metabolism, 33(6), 1155–1170.e1110.

[181] Ling, C., Bacos, K., & Ronn, T. (2022). Epigenetics of type 2 diabetes mellitus and weight change - A tool for precision medicine? Nature Reviews Endocrinology, 18(7), 433–448.

[182] Kalyani, R. R., Corriere, M., & Ferrucci, L. (2014). Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases. Lancet Diabetes & Endocrinology, 2(10), 819–829.

[183] Umehara, T., Winstanley, Y. E., Andreas, E., Morimoto, A., Williams, E. J., Smith, K. M., Carroll, J., Febbraio, M. A., Shimada, M., Russell, D. L., & Robker, R. L. (2022). Female reproductive life span is extended by targeted removal of fibrotic collagen from the mouse ovary. Science Advances, 8(24), eabn4564.

[184] Lee, G., Kim, Y. Y., Jang, H., Han, J. S., Nahmgoong, H., Park, Y. J., Han, S. M., Cho, C., Lim, S., Noh, J. R., Oh, W. K., Lee, C. H., Kim, S., & Kim, J. B. (2022). SREBP1c-PARP1 axis tunes anti-senescence activity of adipocytes and ameliorates metabolic imbalance in obesity. Cell Metabolism, 34(5), 702–718.e705.

[185] Zhao, P., Wong, K. I., Sun, X., Reilly, S. M., Uhm, M., Liao, Z., Skorobogatko, Y., & Saltiel, A. R. (2018). TBK1 at the crossroads of inflammation and energy homeostasis in adipose tissue. Cell, 172(4), 731–743.e712.

[186] Stern, J. H., & Scherer, P. E. (2015). Adipose tissue biology in 2014: Advances in our understanding of adipose tissue homeostasis. Nature Reviews Endocrinology, 11(2), 71–72.

[187] Yoshino, M., Yoshino, J., Kayser, B. D., Patti, G. J., Franczyk, M. P., Mills, K. F., Sindelar, M., Pietka, T., Patterson, B. W., Imai, S. I., & Klein, S. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372(6547), 1224–1229.

[188] Roh, E., & Kim, M. S. (2020). Hypothalamic NAD(+)-sirtuin axis: Function and regulation. Biomolecules, 10(3), 396.

[189] Abdellatif, M., Sedej, S., & Kroemer, G. (2021). NAD(+) metabolism in cardiac health, aging, and disease. Circulation, 144(22), 1795–1817.

[190] Lampé N., Priksz, D., Erdei, T., Bombicz, M., Juhász, B., Varga, B., Zsuga, J., Szerafin, T., Csanádi, Z., Balla, G., Balla, J., Szilvássy, Z., Gesztelyi, R., & Juhász, B. (2020). Negative inotropic effect of BGP-15 on the human right atrial myocardium. Journal of Clinical Medicine, 9(5), 1434.

[191] Ohlen, S. B., Russell, M. L., Brownstein, M. J., & Lefcort, F. (2017). BGP-15 prevents the death of neurons in a mouse model of familial dysautonomia. Proceedings of the National Academy of Sciences of the United States of America, 114(19), 5035–5040.

[192] Zhang, Q., Zhang, C., Wang, Y., Zhao, J., Li, H., Shen, Q., Wang, X., Ni, M., Ouyang, F., Vinturache, A., Chen, H., & Liu, Z. (2022). Relationship of maternal obesity and vitamin D concentrations with fetal growth in early pregnancy. European Journal of Nutrition, 61(2), 915–924.

[193] Vincent, P. (2019). Intra-articular hyaluronic acid in the symptomatic treatment of knee osteoarthritis: A meta-analysis of single-injection products. Current Therapeutic Research Clinical and Experimental, 90, 39–51.

[194] Burgess, E., Hassmen, P., & Pumpa, K. L. (2017). Determinants of adherence to lifestyle intervention in adults with obesity: A systematic review. Clinical Obesity, 7(3), 123–135.

[195] Gao, X., Sun, C., Zhang, Y., Hu, S., & Li, D. (2022). Dietary supplementation of L-carnitine ameliorates metabolic syndrome independent of trimethylamine N-oxide produced by gut microbes in high-fat diet-induced obese mice. Food & Function, 13(23), 12039–12050.

[196] Li, Q., Lai, X., Sun, L., Cao, J., Ling, C., Zhang, W., Xiang, L., Chen, R., Li, D., & Sun, S. (2020). Antiobesity and anti-inflammation effects of Hakka stir-fried tea of different storage years on high-fat diet-induced obese mice model via activating the AMPK/ACC/CPT1 pathway. Food & Nutrition Research, 64(0).

[197] Lee, Y., Lee, J., Lee, M. S., Chang, E., & Kim, Y. (2021). Chrysanthemum morifolium flower extract ameliorates obesity-induced inflammation and increases the muscle mitochondria content and AMPK/SIRT1 activities in obese rats. Nutrients, 13(10), 3660.

[198] Li, X., Lovell, J. F., Yoon, J., & Chen, X. (2020). Clinical development and potential of photothermal and photodynamic therapies for cancer. Nature Reviews Clinical Oncology, 17(11), 657–674.

[199] Chen, R., Huang, S., Lin, T., Ma, H., Shan, W., Duan, F., Lv, J., Zhang, J., Ren, L., & Nie, L. (2021). Photoacoustic molecular imaging-escorted adipose photodynamic-browning synergy for fighting obesity with virus-like complexes. Nature Nanotechnology, 16(4), 455–465.

[200] Gasparrini, M., Giampieri, F., M. Alvarez Suarez, J., Mazzoni, L., Y. Forbes Hernandez, T., L. Quiles, J., Bullon, P., & Battino, M. (2016). AMPK as a new attractive therapeutic target for disease prevention: The role of dietary compounds AMPK and disease prevention. Current Drug Targets, 17(8), 865–889.

[201] Nani, A., Murtaza, B., Sayed Khan, A., Khan, N. A., & Hichami, A. (2021). Antioxidant and anti-inflammatory potential of polyphenols contained in Mediterranean diet in obesity: Molecular mechanisms. Molecules, 26(4), 985.

[202] Su, C. H., Ho, Y. C., Lee, M. W., Tseng, C. C., Lee, S. S., Hsieh, M. K., Chen, H. H., Lee, C. Y., Wu, S. W., & Kuan, Y. H. (2021). 1-Nitropyrene induced reactive oxygen species-mediated apoptosis in macrophages through AIF nuclear translocation and AMPK/Nrf-2/HO-1 pathway activation. Oxidative Medicine and Cellular Longevity, 2021(1), 9314342.

[203] Liu, F. C., Liao, C. C., Lee, H. C., Chou, A. H., & Yu, H. P. (2022). Effects of corilagin on lipopolysaccharide-induced acute lung injury via regulation of NADPH oxidase 2 and ERK/NF-kappaB signaling pathways in a mouse model. Biology, 11(7), 1058.

[204] Posadino, A. M., Giordo, R., Cossu, A., Nasrallah, G. K., Shaito, A., Abou-Saleh, H., Eid, A. H., & Pintus, G. (2019). Flavin oxidase-induced ROS generation modulates PKC biphasic effect of resveratrol on endothelial cell survival. Biomolecules, 9(6), 209.

RIGHTS & PERMISSIONS

2024 The Author(s). Animal Research and One Health published by John Wiley & Sons Australia, Ltd on behalf of Institute of Animal Science, Chinese Academy of Agricultural Sciences.