Abstract
Adipogenic differentiation from stem cells has become a research target due to the increasing interest in obesity. It has been indicated that adipocytes can secrete palmitic acid methyl ester (PAME), which is able to regulate stem cell proliferation. However, the effects of PAME on adipogenic differentiation in stem cell remain unclear. Here, we present that the adipogenic differentiation medium supplemented with PAME induced the differentiation of rat adipose tissue-derived mesenchymal stem cells (rAD-MSCs) into adipocyte. rAD-MSCs were treated with PAME for 12 days and then subjected to various analyses. The results from the present study show that PAME significantly increased the levels of adipogenic differentiation markers, PPARγ and Gpd1, and enhanced adipogenic differentiation in rAD-MSCs. Furthermore, the level of GPR40/120 protein increased during induction of adipocyte differentiation in rAD-MSCs. Cotreatment with PAME and a GPR40/120 antagonist together inhibited the PAME-enhanced adipogenic differentiation. Moreover, PAME significantly increased phosphorylation of extracellular signal-regulated kinases (ERK), but not AKT and mTOR. Cotreatment with PAME and a GPR40/120 antagonist together inhibited the PAME-enhanced ERK phosphorylation and adipogenic differentiation. PAME also increased the intracellular Ca2+ levels. Cotreatment with PAME and a Ca2+ chelator or a phospholipase C (PLC) inhibitor prevented the PAME-enhanced ERK phosphorylation and adipogenic differentiation. Our data suggest that PAME activated the GPR40/120/PLC-mediated pathway, which in turn increased the intracellular Ca2+ levels, thereby activating the ERK, and eventually enhanced adipogenic differentiation in rAD-MSCs. The findings from the present study might help get insight into the physiological roles and molecular mechanism of PAME in regulating stem cell differentiation.
Highlights
Obesity is a tremendous health problem worldwide
Since GPR40 and GPR120 were coupled with Gq protein, subsequently activating the PI3K-AKT or ERK1/2 signaling pathway, which has been shown to be involved in stem cell differentiation [30, 32], and mTOR is a downstream protein of PI3K-AKT signaling pathway, it has been demonstrated that mTOR upregulates adipogenic transcriptional factors [33]; we further investigated whether the PI3K-AKTmTOR or ERK1/2 signaling pathway is involved in the palmitic acid methyl ester (PAME)-enhanced rAD-mesenchymal stem cells (MSCs) adipogenic differentiation
We demonstrated that PAME activated the GPR40/120/phospholipase C (PLC)/extracellular signal-regulated kinases (ERK) signaling pathway, leading to the enhancement of adipogenic differentiation in rAD-MSCs
Summary
Excess adiposity is an established risk factor for metabolic diseases, heart diseases, hypertension, stroke, and several types of cancer [1]. Obesity is defined as an excessive accumulation of adipose tissue and can be divided into two main types: hyperplasia (adipocyte number increase) and hypertrophy. Several studies have demonstrated that the adipocyte number increases when body fat reaches 25% of the total body weight in children and adults [2, 3]. Adipocyte precursors from obese subjects proliferate more rapidly in culture than the cells from lean individuals [4, 5]. The mesenchymal stem cells (MSCs), a major source of adipocyte generation in adipose tissue, can increase adipocyte number [1, 6]
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