CRTC3 Regulates the Lipid Metabolism and Adipogenic Differentiation of Porcine Intramuscular and Subcutaneous Adipocytes by Activating the Calcium Pathway.

Abstract

Fat deposition, especially the intramuscular (IM) fat deposition, is directly associated with meat quality. The cyclic adenosine monophosphate (cAMP)-responsive element binding-protein (CREB)-regulated transcription coactivator 3 (CRTC3) plays an important role in energy metabolism and various biological processes. The expression of porcine CRTC3 in skeletal muscle is positively associated with intramuscular fat deposition and possesses the capacity to control the intramuscular (IM) adipocyte morphology. However, the metabolic effects and transcriptional mechanism of CRTC3 in porcine intramuscular (IM) adipocytes as well as the regulatory mechanism of CRTC3 on porcine adipocyte differentiation have not been studied. Here, we utilized metabolomics and RNA sequencing (RNA-seq) to determine the metabolic and transcriptome profiles of CRTC3-overexpressing IM adipocytes. Moreover, the effect and regulation mechanism of CRTC3 on porcine IM and subcutaneous (SC) adipocyte differentiation were also studied. Our results showed that CRTC3 overexpression dramatically altered the metabolites in IM adipocytes. Glycerophospholipid (GP) metabolism and related genes were significantly changed in CRTC3-overexpressing IM adipocytes. Moreover, we demonstrated that CRTC3 overexpression promotes adipogenic differentiation by upregulating the Ca2+-cAMP signaling pathway in IM and SC adipocytes. We showed alterations in metabolites and in the expression of genes involved in lipid metabolism in CRTC3-overexpressing adipocytes and demonstrated the regulatory mechanism of CRTC3 on the adipogenic differentiation of porcine adipocytes. These results provide new insights into the regulatory roles of CRTC3 in porcine adipocytes, which could be an important target to regulate fat deposition in animals.