MiR-144-3p Targets FoxO1 to Reduce Its Regulation of Adiponectin and Promote Adipogenesis

Abstract

MicroRNAs (miRNAs), as a series of important short-chain non-coding RNAs, play an important post-transcriptional role in many biological activities, including adipogenesis. miR-144 is significantly upregulated in type II diabetes (T2D), and is considered to be an important biomarker for T2D. However, although the occurrence of T2D is inextricably linked to adipogenesis, whether miR-144 directly regulates adipogenesis remains to be further explored. In this paper, we demonstrate that miR-144 has a higher expression level in a porcine high backfat group, and it has a significant positive effect on promoting the differentiation of pre-adipocytes. FoxO1 is a target gene of miR-144, and inhibits the differentiation of pre-adipocytes. On the other hand, we demonstrate that FoxO1 can bind to the AdipoQ gene promoter, then regulate the AdipoQ expression by binding to the FoxO1 binding site in the AdipoQ promoter -1,499 to -1,489 bp and -1,238 to -1,228 bp regions, especially the -1,499 to -1,489 bp region. Meanwhile, miR-144 and FoxO1 co-expressional research has also shown that both factors regulate adipogenesis. To sum up, our research indicates that miR-144 targets FoxO1, thus reducing its expression and inhibiting its promotional effect on adiponectin, thereby alleviating the inhibitory effect of adiponectin on adipogenesis.

An Update in Epigenetics in Metabolic-Associated Fatty Liver Disease

“…Remarkably, Lin et al demonstrated that miR-144 targets Foxo1 , thus reducing its expression and inhibiting its promotional effect on adiponectin, thereby alleviating the inhibitory effect of adiponectin on adipogenesis in an experimental model ( 102 ). A study performed by Komaya et al reported that miR-33b showed high expression in the liver, and its expression was increased in response to cholesterol overload, using genetically modified mice, miR-33 knockout mice, and miR-33b Knock in mice; as a result, miR-33b showed increased atherogenic potential ( 103 ).…”

Emerging Roles of Non-Coding RNAs in the Feed Efficiency of Livestock Species

“…Some miRNAs detected in skeletal muscle correspond to two key pathways: one related to mitochondria and energy metabolism and the other related to skeletal muscle growth. Several miRNAs, including miR-338, miR-335, and miR-144, are related to mitochondria and energy metabolism [ 20 , 21 ]. More than 90% of cellular energy is produced by mitochondria through oxidative phosphorylation (OXPHOS) [ 55 ].…”

microRNAs in Human Adipose Tissue Physiology and Dysfunction

“…This takes place in the case of miR-144 and FOXO1. miR-144 targets FoxO1 mRNA, thus reducing its expression and inhibiting its promotional effect on adiponectin, thereby alleviating the inhibitory effect of adiponectin on adipogenesis in porcine preadipocytes [ 120 ]. In human obesity, serum miR-144 is a marker of insulin resistance, and its levels are elevated in SAT and decrease after weight loss intervention [ 9 , 82 , 121 ].…”