Energy Homeostasis In Tissues Research Articles

Intercellular Transport of Mitochondria: Molecular Mechanisms and Role in Maintaining Energy Homeostasis in Tissues

Intercellular Transport of Mitochondria: Molecular Mechanisms and Role in Maintaining Energy Homeostasis in Tissues

A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies.

5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.

Elafibranor interrupts adipose dysfunction-mediated gut and liver injury in mice with alcoholic steatohepatitis.

Background: Reversal of alcohol-induced peroxisome proliferator-activated receptor (PPAR) α (PPARα) and PPARδ dysfunction has been reported to decrease the severity of alcoholic steatohepatitis (ASH). Autophagy is essential for cell survival and tissue energy homeostasis. Emerging evidence indicates that alcohol-induced adipose tissue (AT) autophagy dysfunction contributes to injury in the intestine, liver, and AT of ASH. Methods: The effects and mechanisms of dual PPARα/δ agonist elafibranor on autophagy stimulation were investigated using mice with ASH. Results: C57BL/6 mice on ethanol diet showed AT dysfunction, disrupted intestinal barrier, and ASH, which was accompanied by alcohol-mediated decrease in PPARα, PPARδ, and autophagy levels in intestine, liver, and AT. Chronic treatment with elafibranor attenuated AT apoptosis and inflammation by restoration of tissue PPARα, PPARδ, and autophagy levels. In ASH mice, alcohol-induced AT dysfunction along with increased fatty acid (FA) uptake and decreased free FA (FFA) release from AT was inhibited by elafibranor. The improvement of AT autophagy dysfunction by elafibranor alleviated inflammation and apoptosis-mediated intestinal epithelial disruption in ASH mice. Acute elafibranor incubation inhibited ethanol-induced ASH-mice-sera-enhanced autophagy dysfunction, apoptosis, barrier disruption, and intracellular steatosis in Caco-2 cells and primary hepatocytes (PHs). Conclusion: Altogether, these findings demonstrated that the PPARα/δ agonist, elafibranor, decreased the severity of liver injury by restoration of alcohol-suppressed AT autophagy function and by decreasing the release of apoptotic markers, inflammatory cytokines, and FFA, thereby reducing intestinal epithelium disruption and liver inflammation/apoptosis/steatosis in ASH mice. These data suggest that dual PPAR agonists can serve as potential therapeutic agents for the management of ASH.

Gill bioenergetics dysfunction and oxidative damage induced by thiamethoxam exposure as relevant toxicological mechanisms in freshwater silver catfish Rhamdia quelen

Thiamethoxam is a neonicotinoid pesticide utilized on a worldwide scale, it has been reported in freshwater ecosystems, and detected in fishery products. Nevertheless, there is a lack of information about thiamethoxam sublethal effects on the gills of freshwater fish, principally linked to energetic metabolism. In this context, creatine kinase (CK) is an enzyme of the phosphoryl transfer network that provides a temporal and spatial energy buffer to maintain cellular energy homeostasis in tissues with high energy requirements, such as gills. Based on this evidence, the aim of this study was to evaluate whether exposure to thiamethoxam impairs the cytosolic and mitochondrial CK activities in gills of Rhamdia quelen, and the involvement of oxidative stress in the energetic imbalance. Branchial CK (cytosolic and mitochondrial) activity and sodium‑potassium pump (Na+, K+-ATPase) were inhibited, and adenosine triphosphate (ATP) levels decreased after 96 h exposure to 1.125 and 3.75 μg/L thiamethoxam compared to the control group. Moreover, levels of branchial thiobarbituric acid reactive substances (TBARS) and protein carbonylation increased at 3.75 μg/L thiamethoxam after 96 h of exposure compared to the control group, while the non-protein thiol (NPSH) content did not differ between groups. It is important to emphasize that all evaluated parameters did not recover after 48 h in clean water. To summarize, the data presented here clearly demonstrated that thiamethoxan exposure severely impairs cytosolic and mitochondrial CK activities, a key enzyme for gill energy buffering to maintain cellular energy homeostasis, and this effect appears to be mediated by oxidation of lipid and protein molecules, which consequently thereby induces oxidative stress.