<i>Mstn</i> knockdown promotes intramuscular fatty acid metabolism by β oxidation via the up-regulation of <i>Cpt1b</i>.

Yanan Guo; Ruyan Yang; Zhiyu Zhang; Dulan Bao; Ying Sun; Lei Yang; Guangpeng LI; Li Gao

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Mstn knockdown promotes intramuscular fatty acid metabolism by β oxidation via the up-regulation of Cpt1b.

Author: Yanan GUO ¹ ; Ruyan YANG ¹ ; Zhiyu ZHANG ¹ ; Dulan BAO ¹ ; Ying SUN ¹ ; Lei YANG ² ; Guangpeng LI ² ; Li GAO ¹
Author Information

1. Faculty of Biology Science and Technology, Baotou Teacher's College, Baotou 014030, Inner Mongolia, China.
2. State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, Inner Mongolia, China.
Publication Type:Journal Article
Keywords: Cpt1b; Mstn gene; RNA interference; fatty acid metabolism; β oxidation
MeSH: Animals; Carnitine O-Palmitoyltransferase/metabolism*; Fatty Acids; Lipid Metabolism; Mice; Mice, Knockout; Muscle, Skeletal/metabolism*; Myostatin/metabolism*; Oxidation-Reduction; Up-Regulation
From: Chinese Journal of Biotechnology 2022;38(8):3076-3089
CountryChina
Language:Chinese
Abstract: Myostatin (Mstn) is known as growth/differentiation factor-8 (GDF-8). Knockout or knockdown of Mstn gene promotes muscle development and reduces fat content. Here we prepared Mstn knockdown mice by RNA interference, then the morphology of the skeletal muscle, the content of triglyceride (TG), the content and composition of fatty acids in the skeletal muscle were detected. The expression of Mstn reduced in muscle of Mstn knockdown mice compared to the controls. The cross sectional areas of the skeletal muscle myofibers were significantly larger while the content of TG was less than that of the controls, and the ratios of n-3/n-6 and unsat/sat in the knockdown mice increased significantly. Subsequently, we detected the expression of genes associated with fatty acid metabolism. The expression of the genes associated with lipolysis and fatty acid transportation were up-regulated, while the genes associated with fatty acid synthesis were down-regulated. Of these genes, the up-regulation of a gene associated with β oxidation, Cpt1b, was up-regulated remarkably. We further detected the enzyme activity of CPT1 in skeletal muscle and obtained the same results with gene expression. Moreover, chromatin immunoprecipitation assay was performed and we found that SMAD3, a transcription factor downstream of Mstn, directly binds to the promoter of Cpt1b gene. These results showed that knockdown of Mstn up-regulated the expression of Cpt1b through the binding of SMAD3 to the promoter of Cpt1b, then promoted the β oxidation metabolism of intramuscular fatty acids.