Both non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are highly prevalent metabolic liver diseases. Accumulating epidemiological evidence now indicates that NAFLD and T2DM are strongly associated, yet the causative relationship remains to be elucidated. Liver serves as a hub for nutrient and energy metabolism in the body. Here we demonstrated the pathogenesis linking NAFLD to T2DM through a series of studies and the attenuation of T2DM progression after NALFD improvement in cohort study. We proposed the urgent necessity of NAFLD management and NAFLD drug development, which might be novel therapeutic avenues for T2DM.
Mitochondria function as a hub of the cellular metabolic network. Mitochondrial stress is closely associated with aging and a variety of diseases, including neurodegeneration and cancer. Cells autonomously elicit specific stress responses to cope with mitochondrial stress to maintain mitochondrial homeostasis. Interestingly, mitochondrial stress responses may also be induced in a non-autonomous manner in cells or tissues that are not directly experiencing such stress. Such non-autonomous mitochondrial stress responses are mediated by secreted molecules called mitokines. Due to their significant translational potential in improving human metabolic health, there has been a surge in mitokine-focused research. In this review, we summarize the findings regarding inter-tissue communication of mitochondrial stress in animal models. In addition, we discuss the possibility of mitokine-mediated intercellular mitochondrial communication originating from bacterial quorum sensing.
T cells are one of few cell types in adult mammals that can proliferate extensively and differentiate diversely upon stimulation, which serves as an excellent example to dissect the metabolic basis of cell fate decisions. During the last decade, there has been an explosion of research into the metabolic control of T-cell responses. The roles of common metabolic pathways, including glycolysis, lipid metabolism, and mitochondrial oxidative phosphorylation, in T-cell responses have been well characterized, and their mechanisms of action are starting to emerge. In this review, we present several considerations for T-cell metabolism-focused research, while providing an overview of the metabolic control of T-cell fate decisions during their life journey. We try to synthesize principles that explain the causal relationship between cellular metabolism and T-cell fate decision. We also discuss key unresolved questions and challenges in targeting T-cell metabolism to treat disease.
Essential amino acids (EAAs) are crucial nutrients, whose levels change in rodents and patients with depression. However, how the levels of a single EAA affects depressive behaviors remains elusive. Here, we demonstrate that although deprivation of the EAA leucine has no effect in unstressed mice, it remarkably reverses the depression-like behaviors induced by chronic restraint stress (CRS). This beneficial effect is independent of feeding and is applicable to the dietary deficiency of other EAAs. Furthermore, the effect of leucine deprivation is suppressed by central injection of leucine or mimicked by central injection of leucinol. Moreover, hypothalamic agouti-related peptide (AgRP) neural activity changes during CRS and leucine deprivation, and chemogenetically inhibiting AgRP neurons eliminates the antidepressant effects of leucine deprivation. Finally, the leucine deprivation-regulated behavioral effects are mediated by amino acid sensor general control non-derepressible 2 (GCN2) in AgRP neurons. Taken together, our results suggest a new drug target and/or dietary intervention for the reduction of depressive symptoms.