Differential Gene Expression and Biological Analyses of Primary Hepatocytes Following D-Chiro-Inositol Supplement

Abstract

Dietary supplements have improved the prevention of insulin resistance and metabolic diseases, which became a research hotspot in food science and nutrition. Obesity and insulin resistance, caused by a high-fat diet, eventually result in severe metabolic diseases, can be prevented with the dietary supplement D-chiro-inositol (DCI). In this work, we isolated mice primary hepatocytes with palmitic acid stimulation and DCI was applied to compare and contrast its effects of in primary hepatocyte biology. Before and after intervention with DCI, we used RNA-Seq technology to establish a primary hepatocyte transcriptome gene profile. We found that both PA and DCI cause a wide variation in gene expression. Particularly, we found that DCI plays critical role in this model by acting on glycolysis and gluconeogenesis. Overall, we generated extensive transcripts from primary hepatocytes and uncovered new functions and gene targets for DCI.

d-chiro-Inositol facilitates adiponectin biosynthesis and activates the AMPKα/PPARs pathway to inhibit high-fat diet-induced obesity and liver lipid deposition

“…DCI increased serum adiponectin levels to control obesity and activated adiponectin receptor signaling, which in turn reduced hepatic lipid deposition via the hepatic AdipoRs-AMPKa/PPARa pathway, and validated and explained the prediction of PAinduced primary hepatocytes transcriptomic. 28 Adipose tissue also is a complex endocrine organ and secretes diverse adipokines to influence appetite, immunity, insulin sensitivity, lipid metabolism, and energy homeostasis through a communication network with other tissue. 29 HFD feeding and obesity promote neutrophils and macrophages recruitment to adipose tissue and induce pro-inflammatory and anti-inflammatory cytokines expression.…”

“…DCI increased serum adiponectin levels to control obesity and activated adiponectin receptor signaling, which in turn reduced hepatic lipid deposition via the hepatic AdipoRs-AMPKa/PPARa pathway, and validated and explained the prediction of PA-induced primary hepatocytes transcriptomic. 28…”

Genistein protects against hyperglycemia and fatty liver disease in diet-induced prediabetes mice via activating hepatic insulin signaling pathway

“…To establish a fatty HepG2 cell model, HepG2 was induced by treating with 1mM FFA mixture (oleic acid:palmitic acid = 0.66 mM:0.33 mM) (Solarbio Co., Ltd., Beijing, China) for 24 h. The differentiation of HepG2 cells was confirmed by measuring triglyceride levels. Primary hepatocytes were isolated as previously reported ( 19 ). Briefly, primary hepatocytes were isolated from male C57BL/6 mice with HBSS (Hyclone, UT, USA) and collagenase IV (Gibco, NY, USA), seeded in a six-well plate in William’s E medium for 24 h. The cells were treated with genistein for 24 h after starved for 4 h.…”