RESUMEN
Myostatin (MSTN) is primarily expressed in skeletal muscle and plays an important role in the regulation of muscle growth and development as well as fat deposition; however, little is known about the molecular mechanism through which MSTN regulates body fat deposition. Therefore, in this study, we sought to identify the signaling pathways through which MSTN regulates fat accumulation in pigs. MSTN knockout (MSTN-/-) pigs showed increased muscle mass, decreased fat mass, and a leaner body composition. In this study, we found that the adipose tissue of MSTN-/- pigs exhibits the characteristics of beige adipose tissue, and the mRNA expression levels of beige adipose marker genes, including UCP3, Cidea, and CD137, were significantly increased. Remarkably, the observed beige phenotype was not adipocyte autonomous but rather caused by muscle-secreted myokine interleukin (IL)-6. This occurrence results in increased AMP-activated protein kinase (AMPK) phosphorylation in adipose tissue, which subsequently activates peroxisome proliferator-activated receptor gamma coactivator 1α and the conversion of white adipocytes to beige in pigs. Therefore, we concluded that MSTN deficiency leads to increased IL-6 secretion in skeletal muscle and activates AMPK in adipocytes, thereby increasing the beige adipose tissue in MSTN-/- pigs.
Asunto(s)
Tejido Adiposo Beige , Miostatina , Tejido Adiposo/metabolismo , Tejido Adiposo Beige/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Técnicas de Inactivación de Genes/veterinaria , Interleucina-6/genética , Músculo Esquelético/metabolismo , Miostatina/genética , PorcinosRESUMEN
M344 is a novel histone deacetylase inhibitor. There is no report on the effect of M344 treatment on the development of pig embryos after somatic cell nuclear transfer (SCNT). In the present study, we investigated the effect of M344 on the blastocyst formation rate in cloned embryos, acetylation level of histone H4 lysine 12 (AcH4K12), and the expression of pluripotency-related genes , , and . Our results indicated that treatment with 5 µ M344 for 6 h improved the development of porcine embryos, in comparison with the untreated group (25.1% ± 5.0 vs. 10.9% ± 2.4; < 0.05). Moreover, M344-treated embryos had increased average fluorescence intensity of AcH4K12 at the pseudo-pronuclear stage ( < 0.05). However, no differences exist in Oct4, NANOG, and SOX2 expression in M344-treated and untreated SCNT blastocysts. In evaluating the effect of M344 on in vivo development, 845 M344-treated embryos were transferred into 3 surrogates, 1 of whom became pregnant and developed 3 fetuses. These findings suggested that M344 elevated the level of histone acetylation, facilitated the nuclear programming, and subsequently improved the developmental competence of pig SCNT embryos.