Dataset Information

Myostatin regulates fatty acid desaturation and fat deposition through MEF2C/miR222/SCD5 cascade in pigs.

ABSTRACT: Myostatin (MSTN), associated with the "double muscling" phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.

SUBMITTER: Ren H

PROVIDER: S-EPMC7584575 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Myostatin regulates fatty acid desaturation and fat deposition through MEF2C/miR222/SCD5 cascade in pigs.

Ren Hongyan H Xiao Wei W Qin Xingliang X Cai Gangzhi G Chen Hao H Hua Zaidong Z Cheng Cheng C Li Xinglei X Hua Wenjun W Xiao Hongwei H Zhang Liping L Dai Jiali J Zheng Xinmin X Zhu Zhe Z Qian Chong C Yao Jie J Bi Yanzhen Y

Communications biology 20201023 1

Myostatin (MSTN), associated with the "double muscling" phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected t ...[more]

PMID: 33097765

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Project description:Trimethylamine oxide (TMAO) is a microbiota-derived metabolite, and numerous studies have shown that it could regulate fat metabolism in humans and mice. However, few studies have focused on the effects of TMAO on fat deposition in growing-finishing pigs. This study aimed to investigate the effect of TMAO on fat deposition and intestinal microbiota in growing-finishing pigs. Sixteen growing pigs were randomly divided into 2 groups and fed with a basal diet with 0 or 1 g/kg TMAO for 149 d. The intestinal microbial profiles, fat deposition indexes, and fatty acid profiles were measured. These results showed that TMAO supplementation had a tendency to decrease lean body mass (P < 0.1) and significantly increased backfat thickness (P < 0.05), but it did not affect growth performance. TMAO significantly increased total protein (TP) concentration, and reduced alkaline phosphatase (ALP) concentration in serum (P < 0.05). TMAO increased the α diversity of the ileal microbiota community (P < 0.05), and it did not affect the colonic microbial community. TMAO supplementation significantly increased acetate content in the ileum, and Proteobacteria and Escherichia-Shigella were significantly enriched in the TMAO group (P < 0.05). In addition, TMAO decreased fat content, as well as the ratio of linoleic acid, n-6 polyunsaturated fatty acids (PUFA), and PUFA in the liver (P < 0.05). On the contrary, TMAO increased intramuscular fat content of the longissimus dorsi muscle, whereas the C18:2n6c ratio was increased, and the n-6 PUFA:PUFA ratio was decreased (P < 0.05). In vitro, 1 mM TMAO treatment significantly upregulated the expression of FASN and SREBP1 in C2C12 cells (P < 0.05). Nevertheless, TMAO also increased adipocyte area and decreased the CPT-1B expression in subcutaneous fat (P < 0.05). Taken together, TMAO supplementation regulated ileal microbial composition and acetate production, and regulated fat distribution and fatty acid composition in growing-finishing pigs. These results provide new insights for understanding the role of TMAO in humans and animals.

Dataset Information

Myostatin regulates fatty acid desaturation and fat deposition through MEF2C/miR222/SCD5 cascade in pigs.

Publications

Myostatin regulates fatty acid desaturation and fat deposition through MEF2C/miR222/SCD5 cascade in pigs.

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