B Vitamins Can Reduce Body Weight Gain by Increasing Metabolism-related Enzyme Activities in Rats Fed on a High-Fat Diet

Abstract

B vitamins are enzyme cofactors that play an important role in energy metabolism. The aim of this study was to elucidate whether B vitamin administration can reduce body weight (BW) gain by improving energy metabolism-related enzyme activities in rats fed on a highfat diet. Fifty rats were randomly assigned to one of the following five groups: control group (C), including rats fed on standard rat chow; four treatment groups (HO, HI, H2, and H3), in which rats were fed on a high-fat diet. Rats in the HI group were treated daily with 100 mg/kg BW thiamine (VB1), 100 mg/kg BW riboflavin (VB2), and 250 mg/kg BW niacin (VPP); rats in the H2 group were treated daily with 100 mg/kg BW pyridoxine (VB6), 100 mg/kg BW cobalamin (VB12), and 5 mg/kg BW folate (FA); and rats in the H3 group were treated daily with all of the B vitamins administered to the HI and H2 groups. After 12 weeks, the BW gains from the initial value were 154.5±58.4 g and 159.1±53.0 g in the HI and C groups, respectively, which were significantly less than the changes in the HO group (285.2±14.8 g, P<0.05). In the HO group, the plasma total cholesterol (CHO) and triglyceride (TG) levels were 1.59±0.30 mmol/L and 1,55±0.40 mmol/L, respectively, which were significantly greater than those in the HI group (1.19±0.18 mmol/L and 0.76±0.34 mmol/L, respectively, P<0.05). The activities of transketolase (TK), glutathione reductase, and Na⁺/K⁺ adenosine triphosphatase were significantly increased in the B vitamin-treated groups and were significantly greater than those in the HO group (P<0.05). Furthermore, the glucose-6-phosphate dehydrogenase, pyruvic acid kinase, and succinate dehydrogenase activities also were increased after treatment with B vitamins. Supplementation with B vitamins could effectively reduce BW gain and plasma levels of lipids by improving energy metabolism-related enzyme activities in rats, thus possibly providing potential benefits to humans.

Keywords

B vitamins / obesity / body weight gain / enzyme activities / rats

References

[1] RyanDH. Guidelines for obesity management. Endocrinol Metab Clin North Am, 2016, 45(3): 501-510

[2] GasterM. Reduced TCA flux in diabetic myotubes: A governing influence on the diabetic phenotype?. Biochem Biophys Res Commun, 2009, 387(4): 651-655

[3] Martinez-HervasS, NavarroI, RealJT, et al.. Unsaturated oral fat load test improves glycemia, insulinemia and oxidative stress status in nondiabetic subjects with abdominal obesity. PLoS One, 2016, 1l(8): e0161400

[4] Calderon-SantiagoM, Priego-CapoteF, Galache-OsunaJG, et al.. Method based on GC-MS to study the influence of tricarboxylic acid cycle metabolites on cardiovascular risk factors. J Pharm Biomed Anal, 2013, 74: 178-185

[5] CzibikG, SteeplesV, YavariA, et al.. Citric acid cycle intermediates in cardioprotection. Circ Cardiovasc Genet, 2014, 7(5): 711-719

[6] YuZR, NingY, YuH, et al.. A HPLC-Q-TOF-MSbased urinary metabolomic approach to identification of potential biomarkers of metabolic syndrome. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(2): 276-283

[7] Jardim-MessederD, Moreira-PachecoF. 3-Bromopyruvic Acid Inhibits Tricarboxylic Acid Cycle and Glutaminolysis in HepG2 Cells. Anticancer Res, 2016, 36(5): 2233-2241

[8] ShaerzadehF, MotamediF, KhodagholiF. Inhibition of akt phosphorylation diminishes mitochondrial biogenesis regulators, tricarboxylic acid cycle activity and exacerbates recognition memory deficit in rat model of Alzheimer's disease. Cell Mol Neurobiol, 2014, 34(8): 1223-1233

[9] Echiburu-ChauC, RoyD CalafGM. Metastatic suppressor CD44 is related with oxidative stress in breast cancer cell lines. Int J Oncol, 2011, 39(6): 1481-1489

[10] MatsudaM, ShimomuraI. Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Rev Endocr Metab Disord, 2014, 15(1): 1-10

[11] SoltaniA, ArganiH, RahimipourH, et al.. Oxidized LDL: As a risk factor for cardiovascular disease in renal transplantation. J Bras Nefrol, 2016, 38(2): 147-152

[12] DakshinamurtiK. Vitamins and their derivatives in the prevention and treatment of metabolic syndrome diseases (diabetes). Can J Physiol Pharmacol, 2015, 93(5): 355-362

[13] Mazur-BialyA, PochecE. Vitamin B2 deficiency enhances the pro-inflammatory activity of adipocyte, consequences for insulin resistance and metabolic syndrome development. Life Sci, 2017, 178: 9-16

[14] GanjiSH, QinS, ZhangL, et al.. Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. Atherosclerosis, 2009, 202(1): 68-75

[15] GuerraA, RanganBV, ColemanA, et al.. Effect of extended-release niacin on carotid intima media thickness, reactive hyperemia, and endothelial progenitor cell mobilization: Insights from the atherosclerosis lesion progression intervention using niacin extended release in saphenous vein grafts (ALPINE-SVG) pilot trial. J Invasive Cardiol, 2015, 27(12): 555-560

[16] SuG, SunG, LiuH, et al.. Niacin suppresses progression of atherosclerosis by inhibiting vascular inflammation and apoptosis of vascular smooth muscle cells. Med Sci Monit, 2015, 21: 4081-4089

[17] TanimotoM, GohdaT, KanekoS, et al.. Effect of pyridoxamine (K-163), an inhibitor of advanced glycation end products, on type2 diabetic nephropathy in KK-A(y)/Ta mice. Metabolism, 2007, 56(2): 160-167

[18] HirschS, PoniachickJ, AvendanoM, et al.. Serum folate and homocysteine levels in obese females with non-alcoholic fatty liver. Nutrition, 2005, 21(2): 137-141

[19] MahalleN, KulkarniMV, GargMK, et al.. Vitamin B12 deficiency and hyperhomocysteinemia as correlates of cardiovascular risk factors in Indian subjects with coronary artery disease. J Cardiol, 2013, 61(4): 289-294

[20] Mazur-BialyAI, PochecE, PlytyczB. Immunomodulatory effect of riboflavin deficiency and enrichment -reversible pathological response versus silencing of inflammatory activation. J Physiol Pharmacol, 2015, 66(6): 793-802

[21] SatyanarayanaA, BalakrishnaN, PitlaS, et al.. Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia. PLoS One, 2011, 6(ll): e26747

[22] WilsonCP, WardM, McNultyH, et al.. Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up. Am J Clin Nutr, 2012, 95(3): 766-772

[23] ReevesPG, NielsenFH, FaheyGCJr.. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. JNutr, 1993, 123(11): 1939-1951

[24] ChamberlainBR, ButteryJE, PannallPR. A stable reagent mixture for the whole blood transketolase assay. Ann Clin Biochem, 1996, 33(4): 352-354

[25] HillMH, BradleyA, MushtaqS, et al.. Effects of methodological variation on assessment of riboflavin status using the erythrocyte glutathione reductase activation coefficient assay. Br J Nutr, 2009, 102(2): 273-278

[26] KangLY, McKeeRW, WrightSM, et al.. Metabolic effects of nicotinamide administration in rats. J Nutr, 1983, 113(2): 215-221

[27] KrausD, YangQ, KongD, et al.. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature, 2014, 508(7495): 258-262

[28] KademianM, BechtelM, ZirwasM, et al.. Case reports: new onset flushing due to unauthorized substitution of niacin for nicotinamide. J Drugs Dermatol, 2007, 6: 1220-1221

[29] AlbertCM, CookNR, GazianoJM, et al.. Effect of folic acid and B-vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: A randomized trial. JAMA, 2008, 299(17): 2027-2036

[30] PLoS One, 2015, 10(9):

[31] AmareB, MogesB, MogesF, et al.. Nutritional status and dietary intake of urban residents in Gondar, Northwest Ethiopia. BMC Public Health, 2012, 12: 752

[32] KnightBA, ShieldsBM, BrookA, et al.. Lower circulating B12 is associated with higher obesity and insulin resistance during pregnancy in a non-diabetic white British population. PLoS One, 2015, 10(8): e0135268

[33] WinkvistA, BertzF, EllegardL, et al.. Metabolic risk profile among overweight and obese lactating women in Sweden. PLoS One, 2013, 8(5): e63629

[34] SarnaLK, WuN, WangP, et al.. Folic acid supplementation attenuates high fat diet induced hepatic oxidative stress via regulation of NADPH oxidase. Can J Physiol Pharmacol, 2012, 90(2): 155-165

[35] GasterM, NehlinJO, MinetAD. Impaired TCA cycle flux in mitochondria in skeletal muscle from type2 diabetic subjects: marker or maker of the diabetic phenotype?. Arch Physiol Biochem, 2012, 118(3): 156-189

[36] LeveilleGA. Influence of dietary fat and protein on metabolic and enzymatic activities in adipose tissue of meal-fed rats. JNutr, 1967, 91(1): 25-34

[37] PLoS One, 2013, 8(2):

[38] NemeriaNS, AmbrusA, PatelH, et al.. Human 2-oxoglutarate dehydrogenase complex El component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate. J Biol Chem, 2014, 289(43): 29859-29873

[39] EbaraS, NakaoM, TomodaM, et al.. Vitamin B12 deficiency results in the abnormal regulation of serine dehydratase and tyrosine aminotransferase activities correlated with impairment of the adenylyl cyclase system in rat liver. Br J Nutr, 2008, 99(3): 503-510

[40] KimY, KimEY, SeoYM, et al.. Function of the pentose phosphate pathway and its key enzyme, transketolase, in the regulation of the meiotic cell cycle in oocytes. Clin Exp Reprod Med, 2012, 39(2): 58-67

[41] ShengX, LiuY, LiuC. Theoretical studies on the common catalytic mechanism of transketolase by using simplified models. J Mol Graph Model, 2013, 39: 23-28

[42] Perez-PerezR, Garcia-SantosE, Ortega-DelgadoFJ, et al.. Attenuated metabolism is a hallmark of obesity as revealed by comparative proteomic analysis of human omental adipose tissue. J Proteomics, 2012, 75(3): 783-795

[43] PeralB, CamafeitaE, Fernandez-RealJM, et al.. Tackling the human adipose tissue proteome to gain insight into obesity and related pathologies. Expert Rev Proteomics, 2009, 6(4): 353-361

[44] Codoner-FranchP B, AlberolaA D, CamarasaJV, et al.. Influence of dietary lipids on the erythrocyte antioxidant status of hypercholesterolaemic children. Eur J Pediatr, 2009, 168(3): 321-327

[45] LarsenBR, StoicaA, MacAulayN. Managing brain extracellular K(+) during neuronal activity: The physiological role of the Na(+)/K(+)-ATPase subunit isoforms. Front Physiol, 2016, 7: 141

[46] KumarP, ChandS, MauryaPK. Quercetin-modulated erythrocyte membrane sodium-hydrogen exchanger during human aging: correlation with ATPase's. Arch Physiol Biochem, 2016, 122(3): 141-147

[47] HeinzJ, KropfS, DomröseU, et al.. B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease. Results of a randomized controlled trial circulation, 2010, 121: 1432-1438

[48] HouseAA, EliasziwM, CattranDC, et al.. Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA, 183, 2010, 303: 1603-1609

[49] KernsJC, ArundelC, ChawlaLS. Thiamin deficiency in people with obesity. Adv Nutr, 2015, 6(2): 147-153

[50] KennedyDO, StevensonEJ, JacksonPA, et al.. Multivitamins/minerals modulate cerebral blood-flow and whole-body energy metabolism during cognitive tasks of graded difficulty. Nutr Metab (Lond), 2016, 13: 11

[51] MorrisMS. The role of B vitamins in preventing and treating cognitive impairment and decline. Adv Nutr IntRevJ, 2012, 3: 801-812

[52] MacFarlaneAJ, ShiY, Greene-FinestoneLS. Highdose compared with low-dose vitamin B-12 supplemen use is not associated with higher vitamin B-12 status in children, adolescents, and older adults. J Nutr, 2014, 144: 915-920

[53] BradburyKE, WilliamsSM, GreenTJ, et al.. Differences in erythrocyte folate concentrations in older adults reached steady-state within one year in a twoyear, controlled, 1 mg/d folate supplementation trial. J Nutr, 2012, 142(9): 1633-1637