Chrysanthemi Zawadskii var. Latilobum Attenuates Obesity-Induced Skeletal Muscle Atrophy via Regulation of PRMTs in Skeletal Muscle of Mice.

Ahyoung Yoo,Jiyun Ahn,Chang Hwa Jung,Hyo Deok Seo,Tae Youl Ha,Young Jin Jang

doi:10.3390/ijms21082811

Abstract

As obesity promotes ectopic fat accumulation in skeletal muscle, resulting in impaired skeletal muscle and mitochondria function, it is associated with skeletal muscle loss and dysfunction. This study investigated whether Chrysanthemi zawadskii var. latilobum (CZH) protected mice against obesity-induced skeletal muscle atrophy and the underlying molecular mechanisms. High-fat diet (HFD)-induced obese mice were orally administered either distilled water, low-dose CZH (125 mg/kg), or high-dose CZH (250 mg/kg) for 8 w. CZH reduced obesity-induced increases in inflammatory cytokines levels and skeletal muscle atrophy, which is induced by expression of atrophic genes such as muscle RING-finger protein 1 and muscle atrophy F-box. CZH also improved muscle function according to treadmill running results and increased the muscle fiber size in skeletal muscle. Furthermore, CZH upregulated mRNA and protein levels of protein arginine methyltransferases (PRMT)1 and PRMT7, which subsequently attenuated mitochondrial dysfunction in the skeletal muscle of obese mice. We also observed that CZH significantly decreased PRMT6 mRNA and protein expression, which resulted in decreased muscle atrophy. These results suggest that CZH ameliorated obesity-induced skeletal muscle atrophy in mice via regulation of PRMTs in skeletal muscle.

Highlights

Skeletal muscle atrophy is a debilitating condition associated with decreased protein synthesis and the accelerated degradation of muscle fibers [1]
PatRCMZTH6 ascitgivnaifitecsanFtOlyXOde3carneadstehde PuRbMiqTu6itminR-pNroAteleavsoemls eanddegprraodteaitnioenxppraetshswioanyelienvsakteedlebtayl HmFuDsc(lFei,gruesreul4tEin,Fg, rinesmpeucsticvleelayt)r.oFpuhryth[e1r0m].oWree, loevbeselsrvoefdphthoastpChoZ-HFOsiXgOni3fiicnansktleyledteacl rmeaussecdlePwRaMsTre6dmuRceNdAbyleCveZlHs a(nFdigpurroet4eFin).eTxhperseessrieosnuletlsevinadteicdabtey tHhaFtDCZ(FHigruergeul4aEte,Fd, trheespskeectleivtaellym).uFsculrethPeRrMmTosrei,nlHevFeDls-feodf pmhicoes.pho-FOXO3 in skeletal muscle was reduced by CZH (Figure 4F). These results indicate that CZH regulated the skeletal muscle protein arginine methyltransferases (PRMT) in High-fat diet (HFD)-fed mice
Our results showed that HFD-induced obese mice exhibited a reduction in PRMT1 levels and an increase in PRMT6 levels

Summary

Introduction

Skeletal muscle atrophy is a debilitating condition associated with decreased protein synthesis and the accelerated degradation of muscle fibers [1]. Reduced protein synthesis leads to sharp decreases in skeletal muscle mass, which may result in falls and possible bone fractures [2]. Degradation of muscle fibers is followed by reduced muscle strength and loss of mitochondria in myocytes [3]. Skeletal muscle loss and dysfunction (physical strength, mobility, and vitality) have been associated with obesity, referred to as sarcopenic obesity [4]. Obesity promotes inflammation in adipose tissue, increased lipolysis, and subsequent ectopic fat accumulation in skeletal muscles, which results in impaired skeletal muscles [5]. The skeletal muscle of obese humans exhibits decreased mitochondrial content and reduced function of fatty acid oxidation [6]

Methods

Results

Discussion

Conclusion