Knockdown of long non‐coding RNA Gm10804 suppresses disorders of hepatic glucose and lipid metabolism in diabetes with non‐alcoholic fatty liver disease

Abstract

Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the role of Gm10804, a novel long noncoding RNA (lncRNA), in regulating hepatic glucose and lipid metabolism in DM complicated with NAFLD (DM-NAFLD). Mouse primary hepatocytes exposed to high glucose (HG) were used as a cell model. A mouse DM-NAFLD model was established by high-energy feeding combined with intraperitoneal injection of streptozotocin. The results showed that Gm10804 expression was upregulated in HG-treated hepatocytes and livers from DM-NAFLD mice. Results in hepatocytes in vitro demonstrated that Gm10804 overexpression aggravated, whereas Gm10804 silencing abrogated HG-induced increase in intracellular triglyceride (TG) content, lipid accumulation and expression of hepatic lipogenic proteins (sterol regulatory element-binding proteins 1-c [SREBP-1c] and fatty acid synthase [FAS]) and enzymes for gluconeogenesis (phosphoenolpyruvate carboxykinase [PEPCK] and glucose-6-phosphatase [G6Pase]). Further in vivo assays showed that lentivirus-mediated hepatic knockdown of Gm10804 alleviated hepatic steatosis and lipid accumulation, and decreased expression of hepatic PEPCK, G6Pase, SREBP-1c and FAS in DM-NAFLD mice. In summary, Gm10804 knockdown attenuates hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. Significance of the study: We first discovered that Gm10804 knockdown attenuated hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. These results help to understand the pathogenesis and development of DM-NAFLD and provide some clues for further understanding the regulation of lncRNAs in glucose and lipid metabolism.

Co-expression analysis of lncRNA and mRNA identifies potential adipogenesis regulatory non-coding RNAs involved in the transgenerational effects of tributyltin

“…The second lncRNA with the highest number of mRNA targets, the TBT-downregulated Gm10804. Recently, Li and colleagues [ 36 ] reported that low expression of Gm10804 improves glucose and lipid metabolism disorders in hepatocytes from mice exposed to high glucose, which is of importance as the liver plays a key role in adjusting glucose levels, in turn affecting energy homeostasis in other tissues [ 37 ]. One of the correlated target mRNAs of this lncRNA is the TBT-downregulated Slc27a2 mRNA, also known as FATP2 .…”

6,8-(1,3-Diaminoguanidine) luteolin and its Cr complex show hypoglycemic activities and alter intestinal microbiota composition in type 2 diabetes mice

“…T2DM is a metabolic disorder whose pathogenesis involves the interaction of multiple genes and aspects. 35 The target organ of insulin is the liver, which plays a critical role in maintaining the homeostasis of glucose metabolism. Recent studies have shown that the up- or downregulation of mRNA transcription and protein expression levels of some related genes in the liver glucose metabolism pathway can result in higher FBG and OGTT levels, and eventually lead to diabetes.…”

Bicyclol Regulates Hepatic Gluconeogenesis in Rats with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease by Inhibiting Inflammation

“…Hepatic gluconeogenesis can maintain the glucose and lipid of cellular or whole-body in a steady state, so it plays a vital part in hepatic glucose metabolism (Gastaldelli et al, 2000;Wu et al, 2018). Convincing evidence indicates that overactivated hepatic gluconeogenesis and lipogenesis contribute to the pathogenesis of metabolic disorders, including DM and NAFLD (Cui et al, 2018;Dong et al, 2019;Li et al, 2020). Therefore, one of the important targets in the treatment of T2DM-NAFLD is to inhibit the glycolipid toxicity caused by gluconeogenesis.…”