CTRP6 Regulates Porcine Adipocyte Proliferation and Differentiation by the AdipoR1/MAPK Signaling Pathway

Abstract

Intramuscular fat (IMF) and subcutaneous fat (SCF), which are modulated by adipogenesis of intramuscular and subcutaneous adipocytes, play key roles in pork quality. C1q/tumor necrosis factor-related protein 6 (CTRP6), an adipokine, plays an important role in the differentiation of 3T3-L1 cells. However, the effect and regulatory mechanisms of CTRP6 on porcine adipogenesis, and whether CTRP6 has the same effect on intramuscular and subcutaneous adipocytes, are still unknown. Here, we found that CTRP6 significantly inhibited both adipocyte proliferation assessed by proliferative marker expression, but CTRP6 decreased the proliferation rate of intramuscular adipocytes (IM) to a greater extent than subcutaneous adipocytes (SC). Moreover, CTRP6 promoted the activity of the p38 signaling pathway during the proliferation of both cell types. Nevertheless, in subcutaneous adipocytes, CTRP6 also influenced the phosphorylation of extracellular regulated protein kinases1/2 (p-Erk1/2), but not in intramuscular adipocytes. Additionally, during the differentiation of intramuscular and subcutaneous adipocytes, CTRP6 increased adipogenic genes expression and the level of p-p38, while it decreased the activity of p-Erk1/2. Interestingly, the effect of CTRP6 shRNA or CTRP6 recombinant protein was attenuated by U0126 (a special p-Erk inhibitor) or SB203580 (a special p-p38 inhibitor) in adipocytes. By target gene prediction and experimental validation, we demonstrated that CTRP6 may be a target of miR-29a in porcine adipocytes. Moreover, AdipoR1was identified as a receptor of CTRP6 in intramuscular adipocytes, but not in subcutaneous adipocytes. On the basis of the above findings, we suggest that CTRP6 was the target gene of miR-29a, inhibited intramuscular and subcutaneous adipocyte proliferation, but promoted differentiation by the mitogen-activated protein kinase (MAPK) signaling pathway. These findings indicate that CTRP6 played an essentially regulatory role in fat development.

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

“…It was positively associated with TNF‐α in T2DM patients . CTRP6 KO inhibits adipogenesis and activates PPAR‐γ . This contradiction might be due to diversity in function depending on cell tissue type.…”

Adipose tissue-derived cytokines, CTRPs as biomarkers and therapeutic targets in metabolism and the cardiovascular system

“…Novel metabolic/immune regulator; modulating both inflammation and insulin sensitivity; regulates fat development; alleviates AngII-induced hypertension and vascular endothelial dysfunction; potential therapeutic target for the prevention of skin fibrosis; endogenous complement regulator [5,29,68,69] 7 Adipose tissue, lung Improves insulin sensitivity; beneficial metabolic outcomes in the setting of obesity and diabetes [9,54] 8 (8B) Lung, testis, absent in mice Blocks glioblastoma dissemination within the brain [14,70] 9 (9A,9B) Cardiac tissue, adipose tissue Important in the development of type 2 diabetes; novel metabolic regulator and a new component of the metabolic network that links adipose tissue to lipid metabolism in skeletal muscle and liver; prevents vascular restenosis after angioplasty, hepatic steatosis and hypertension; stabilizes plaque, improves endothelial cell survival and function [12,20,48,[71][72][73] 10 Eye, adipose tissue Regulates metabolism, adipose tissue homeostasis [3,23] 11 Adipose tissue New regulator of adipogenesis; maintains adipose tissue homeostasis [3,74] 12 Adipose tissue Novel biomarkers for the prediction and early diagnosis of T2DM; regulates glucose and lipid metabolism and whole-body glucose homeostasis [24,50,51,75,76] 13 Adipose tissue, brain Associated with increased risk of T2DM and coronary artery disease and non-alcoholic fatty liver disease; negative association with metabolism; modulates whole-body energy balance [2,24,27,77,78] 14 Brain, adipose tissue Promotes tissue regeneration, and recovery of ischemic heart disease; maintains adipose tissue homeostasis by generating complexes with CTRP11 [74] 15 Skeletal muscle Modulates energy homeostasis and metabolic circuit; modulates inter-tissue crosstalk [21,79] ISR: in-stent restenosis; PCI: percutaneous coronary intervention; DES: d...…”

Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep

“…Whether these candidate genes play an important role in lipid deposition remains to be studied [54]. In addition, although various pathways, such as the "Wnt signaling pathway," "MAPK signaling pathway," "AMPK signaling pathway" and "PPAR signaling pathway" were not significantly enriched, they were related to fat development and deposition [56][57][58][59]. Therefore, the differentially expressed lncRNAs involved in the aforementioned pathways may play an important role in the process of lipid deposition and deserve further study.…”