Muscle Conditional Medium Reduces Intramuscular Adipocyte Differentiation and Lipid Accumulation through Regulating Insulin Signaling.

Haiyin Han,Ye Tian,Zaohang Jiang,Kaiqing Liu,Wei Wei,Jie Chen,Weiwei Chu

doi:10.3390/ijms18081799

Abstract

Due to the paracrine effects of skeletal muscle, the lipid metabolism of porcine intramuscular (i.m.) preadipocytes was different from that of subcutaneous (s.c.) preadipocytes. To investigate the development of i.m. preadipocytes in vivo, the s.c. preadipocytes were cultured with muscle conditional cultured medium (MCM) for approximating extracellular micro-environment of the i.m. preadipocytes. Insulin signaling plays a fundamental role in porcine adipocyte differentiation. The expression levels of insulin receptor (INSR) and insulin-like growth factor 1 receptor (IGF-1R) in i.m. Preadipocytes were higher than that in s.c. preadipocytes. The effects of MCM on adipocyte differentiation, lipid metabolism and insulin signaling transdution were verified. MCM induced the apoptosis of s.c. preadipocytes but not of s.c. adipocytes. Moreover, MCM inhibited adipocyte differentiation at pre-differentiation and early stages of differentiation, while the expression levels of INSR and IGF-1R were increased. Furthermore, MCM treatment increased adipocyte lipolysis and fatty acid oxidation through induction of genes involved in lipolysis, thermogenesis, and fatty acid oxidation in mitochondria. Consistent with the above, treatment of s.c. adipocytes with MCM upregulated mitochondrial biogenesis. Taken together, MCM can approximate the muscle micro-environment and reduce intramuscular adipocyte differentiation and lipid accumulation via regulating insulin signaling.

Highlights

The deposition of fat in muscle, recognized by the intramuscular fat (IMF), is an important meat quality
Before the appearance of responsiveness of insulin receptor (INSR) to insulin during later stages of adipocyte differentiation, insulin mediates its early adipogenic effect via insulin-like growth factor-1 receptors (IGF-1R), which is initiated by activation of the tyrosine kinase at the cell surface [10]
All of these findings suggested the molecular mechanism of insulin action on adipocyte differentiation, but the effects of insulin signaling on porcine intramuscular adipogenesis are not well understand

Summary

Introduction

The deposition of fat in muscle, recognized by the intramuscular fat (IMF), is an important meat quality. The differentiation of preadipocytes to mature adipocytes includes activation of adipogenic gene expression and induction of insulin sensitivity [4]. Before the appearance of responsiveness of insulin receptor (INSR) to insulin during later stages of adipocyte differentiation, insulin mediates its early adipogenic effect via insulin-like growth factor-1 receptors (IGF-1R), which is initiated by activation of the tyrosine kinase at the cell surface [10]. Insulin receptor was required for the full differentiation response because of the impaired adipocyte differentiation that was associated with decreased insulin receptor expression [13] All of these findings suggested the molecular mechanism of insulin action on adipocyte differentiation, but the effects of insulin signaling on porcine intramuscular adipogenesis are not well understand. We turned our attention to the most proximal steps of insulin signaling for further study, including the INSR/IGF-1R and the major direct substrate, IRS-1

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