Hepatic lipid homeostasis by peroxisome proliferator-activated receptor gamma 2

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ or PPARG) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. It plays a master role in the differentiation and proliferation of adipose tissues. It has two major isoforms, PPARγ1 and PPARγ2, encoded from a single gene using two separate promoters and alternative splicing. Among them, PPARγ2 is most abundantly expressed in adipocytes and plays major adipogenic and lipogenic roles in the tissue. Furthermore, it has been shown that PPARγ2 is also expressed in the liver, specifically in hepatocytes, and its expression level positively correlates with fat accumulation induced by pathological conditions such as obesity and diabetes. Knockout of the hepatic Pparg gene ameliorates hepatic steatosis induced by diet or genetic manipulations. Transcriptional activation of Pparg in the liver induces the adipogenic program to store fatty acids in lipid droplets as observed in adipocytes. Understanding how the hepatic Pparg gene expression is regulated will help develop preventative and therapeutic treatments for non-alcoholic fatty liver disease (NAFLD). Due to the potential adverse effect of hepatic Pparg gene deletion on peripheral tissue functions, therapeutic interventions that target PPARγ for fatty liver diseases require fine-tuning of this gene’s expression and transcriptional activity.

Synbiotic kefir lowered peroxisome proliferator activated receptor gamma (PPARγ) gene expression in rat fed high-fat and high-fructose diet

“…Based on Table 7 and Table 8 showed that the change in PPARγ2 gene expression in liver tissue was higher than adipose tissue. Normally, PPARγ2 is most abundantly expressed in adipocytes and plays major adipogenic and lipogenic roles in the tissue (Lee et al, 2018). Because the rats in the present study received high fat and high fructose diet, it was possible to cause fatty liver.…”

“…Because the rats in the present study received high fat and high fructose diet, it was possible to cause fatty liver. According to Souza-Mello (2015), in non-alcoholic fatty liver disease (NAFLD) showed a high abnormality of PPARγ expression in the liver (Lee et al, 2018).…”

“…These results was in accordance with the results by May et al (2015), that PPARγ expression level was signi cantly higher in high fat diet than normal diet rats which is mainly related to fat formation. PPARγ2 is also expressed in the liver, speci cally in hepatocytes, and its expression level positively correlates with fat accumulation induced by pathological conditions such as obesity and diabetes (Lee et al, 2018).…”

Emergent properties of HNF4α-PPARγ network may drive consequent phenotypic plasticity in NAFLD

“…Many genes involved in adipogenic programs play a key role in the initiation and progression of NAFLD [7]. Peroxisome proliferation-activated receptor gamma 2 (PPARγ), a master regulator of adipogenesis [14], is frequently upregulated in NAFLD [15]. Similarly, sterol regulatory binding element protein-1c, SREBP-1c (protein coded by the gene SREBF1), a major driver of hepatic DNL, is upregulated in NAFLD [7].…”

“…Similarly, sterol regulatory binding element protein-1c, SREBP-1c (protein coded by the gene SREBF1), a major driver of hepatic DNL, is upregulated in NAFLD [7]. Consequently, many coregulators and downstream target genes of PPARγ and SREBP-1c are also perturbed in the context of NAFLD [15]. Another intriguing observation about NAFLD patients is their lower levels of hallmark liver tissue maintenance genes of the liver such as Hepatocyte Nuclear Factor 4α (HNF4α) and…”