Regulation of Liver Glucose and Lipid Metabolism by Transcriptional Factors and Coactivators

Abstract

The prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide is on the rise and NAFLD is becoming the most common cause of chronic liver disease. In the USA, NAFLD affects over 30% of the population, with similar occurrence rates reported from Europe and Asia. This is due to the global increase in obesity and type 2 diabetes mellitus (T2DM) because patients with obesity and T2DM commonly have NAFLD, and patients with NAFLD are often obese and have T2DM with insulin resistance and dyslipidemia as well as hypertriglyceridemia. Excessive accumulation of triglycerides is a hallmark of NAFLD and NAFLD is now recognized as the liver disease component of metabolic syndrome. Liver glucose and lipid metabolisms are intertwined and carbon flux can be used to generate glucose or lipids; therefore, in this review we discuss the important transcription factors and coactivators that regulate glucose and lipid metabolism.

Esculeogenin A, a Glycan from Tomato, Alleviates Nonalcoholic Fatty Liver Disease in Rats through Hypolipidemic, Antioxidant, and Anti-Inflammatory Effects

“…Opposing REBP1c, insulin, and growth hormones stimulate this condition, whereas adiponectin stimulates hepatic PPARα [73][74][75]. Therefore, the hyperinsulinemia and adiponectin resistance observed in HFD-fed animals in this study triggered the suppression of the PPARα/CPT1 axis [56]. On the other side of this study, dose-response reductions in the serum and hepatic levels were also observed in the livers of all rats fed an HFD and co-treated with ESGA and were associated with similar dose-response reversals in the hepatic expression of SREBP1, ACC, PPARα, and CPT1.…”

“…Hypolipidemic agents, such as statins, attenuate hepatic steatosis and reduce the risk of cardiovascular disorders [52][53][54]. In the liver, lipid synthesis is a tightly regulated mechanism that involves a delicate balance between de novo lipogenesis (DNL) and FA oxidation, controlled by numerous transcription factors [55,56]. In general, the transcription factor SREBP1 stimulates DNL by increasing the transcription of several lipogenic genes, such as fatty acid oxidase and acetyl CoA carboxylase (ACC) [57].…”

“…These results can be explained by the hyperglycemia, hyperinsulinemia, and hyperadiponectinemia observed in these rats, as well as by the higher hepatic levels of ROS and inflammatory cytokines. Indeed, hyperinsulinemia, hyperglycemia, ROS, and inflammatory cytokines can rapidly upregulate and activate SREBP1c and cause severe hepatic steatosis, as seen in obesity, NAFLD, and the early stages of T2DM [56,[70][71][72]. Opposing REBP1c, insulin, and growth hormones stimulate this condition, whereas adiponectin stimulates hepatic PPARα [73][74][75].…”

Exposure to the pesticide tefluthrin causes developmental neurotoxicity in zebrafish

“…4B ). Overall, the enrichment of transcription factors that regulate liver metabolic homeostasis, such as LXR, FXR, HNF4A, CEBPB, CREB1, and FOXO3 (50) are indicative of perturbations in the liver transcriptional network. Furthermore, liver toxicity endpoints were among the top enriched toxicity pathways ( Fig.…”

Identification and characterization of structural variants related to meat quality in pigs using chromosome-level genome assemblies

“…The actin filaments perform diverse cellular functions including cell adhesion and directly or indirectly regulate lipid synthesis and metabolism [ 52 ]. Also, the phosphorylation has been reported to be involved in the hepatic lipid metabolism [ 53 ]. The blood circulation also has been reported to affect IMF traits in chickens [ 54 ].…”