1,25-Dihydroxyvitamin D3 modulates adipogenesis of human adipose-derived mesenchymal stem cells dose-dependently

Amin Salehpour,Ali Asghar Farshad,Farzad Shidfar,Asal Neshatbini Tehrani,Saeed Mohammadi,Mehdi Hedayati

doi:10.1186/s12986-021-00561-4

Abstract

Purpose1,25-dihydroxyvitamin D3 may regulate adipogenesis in adipocytes in-vitro, but little is known about possible molecular mechanisms related to the inhibitory effect of 1,25-dihydroxyvitamin D3 on adipogenesis in humans҆ adipose tissue.MethodologyIn this study, human adipose-derived mesenchymal stem cells (hASCs) were cultured for 14 days in adipogenic differentiation media containing concentrations of 1,25-dihydroxyvitamin D3 (10−10–10−8 M). The extent of adipogenic differentiation in ASCs was assessed by Oil Red O staining and quantitative polymerase chain reaction (PCR) to determine expression levels of key adipogenic markers.ResultsOur results showed that vitamin D receptor (VDR), as a mediator of most actions of 1,25-dihydroxyvitamin D3, glucose trasporter-4 (GLUT4),and fatty acid binding protein-4 (FABP4) was expressed in vitamin D-treated hASCs. However, the protein level of these markers was lower than the control group. Treatment of human preadipocytes with 1,25-dihydroxyvitamin D3 significantly altered expression of adipogenic markers and triglyceride accumulation in a dose-dependent manner. 1,25-dihydroxyvitamin D3 at concentration of 10−8 M enhanced expression of sterol regulatory element-binding protein-1c (SREBP1c), CCAAT-enhancer-binding protein-β (C/EBPβ), a mitotic clonal expansion, peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FASN), a marker of de novo lipogenesis,and lipoprotein lipase (LPL).ConclusionOur findings revealed that 1,25-dihydroxyvitamin D3 may provoke adipocyte development in critical periods of adipogenesis at concentration of 10−8 M, thereby leading to a greater risk of obesity in adulthood and an augmented risk of obesity-related diseases including diabetes, cardiovascular diseases, and some cancers.

Highlights

Obesity characterized by accumulation of exorbitant triglyceride in adipose tissue depending on hypertrophyVitamin D is one of the fat-soluble vitamins with exogenous and endogenous source in body
Expression of CCAAT-enhancer-binding protein-β (C/EBPβ) was significantly downregulated by treatment with 1,25-Dihydroxyvitamin D3 at a concentration of 10−8M on day 14 (P=0.008) and there was a fluctuation in C/EBPβ mRNA expression by treatment with 1,25-Dihydroxyvitamin D3 at a concentration of 10−10M along with downregulation on day 6 (P
The anti-lipogenic outcome of 1,25-Dihydroxyvitamin D3 through adipogenesis was accompanied by alterations in the expression of adipogenic markers involved in metabolism of adipose tissue

Summary

Introduction

Obesity characterized by accumulation of exorbitant triglyceride in adipose tissue depending on hypertrophy. Vitamin D is one of the fat-soluble vitamins with exogenous and endogenous source in body. Salehpour et al Nutr Metab (Lond) (2021) 18:29. (UVB) irradiation in the skin leads to the increase in the level of vitamin D in body through conversion of 7-dehydrocholestrol into cholecalciferol (vitamin D3). Diet can provide the body’s requirement for vitamin D as well. For activating vitamin D thoroughly, it should be hydroxylated twice. Under reaction with 25-hyrodxylases, previtamin D is turned into 25-hidroxyvitamin D3 (25(OH) D), as circulating form of vitamin D. 1,25-dihydroxy-vitamin D (1,25(OH)2D) as a bioactive form of vitamin D metabolite and activator of vitamin D receptor (VDR) is obtained from 25(OH)D through action of 1α-hydroxylase [5]

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