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

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.

Mitochondrial dysfunction in skeletal muscle contributes to the development of acute insulin resistance in mice

“…This analysis must be carefully considered under conditions of muscle atrophy where the nuclear density is increased 39 . We and another group demonstrated that a HFD causes muscle atrophy 40,41 . In the current study, however, the decrease of muscle mtDNA content under acute IR conditions was negligible because 2 weeks of HFD feeding was insufficient to induce muscle atrophy.…”

Dietary Luteolin: A Narrative Review Focusing on Its Pharmacokinetic Properties and Effects on Glycolipid Metabolism

“…Also, in vivo , luteolin-enriched Chrysanthemi zawadskii var. latilobum attenuated obesity-induced fat accumulation and metabolic parameters in skeletal muscle by promoting mitochondrial fatty acid import and oxidation, as evidenced by upregulation of protein arginine methyltransferases (PRMT)­1/7 and PGC1α expression (factors that can increase mitochondrial biogenesis and fatty acid β-oxidation) and also the level of oxidative phosphorylation . On the basis of the evidence cited, it seems possible that luteolin may have the ability to control glycolipid homeostasis in skeletal muscle.…”

LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice

“…A key finding here was that LSD1 and PRMT6 overexpression was an early pathological process specifically in skeletal muscle in a cell-autonomous fashion. Although it is not known whether PRMT6 exerts any physiological function in skeletal muscle, its expression is upregulated in pathological settings associated with muscle atrophy, including fasting and muscle-specific PRMT1 knock-out 85 , as well as high-fat diet 25 . LSD1 expression is enhanced during skeletal muscle differentiation and regeneration 49 , 86 , and LSD1 regulates expression of myogenic genes, such as myogenin, and oxidative metabolism genes 48 , 50 , suggesting a physiological role for LSD1 in muscle.…”

“…PRMT6 is a general transcriptional co-repressor yet also is a co-activator of AR 21 . PRMT6 expression is often upregulated in hormone-dependent cancers, such as prostate cancer 22 , 23 , and in mouse models of metabolic syndrome, diabetes, and insulin resistance 24 , 25 —symptoms that also are present in ~50% of SBMA patients 5 . Previous transcriptomic analysis identified significant upregulation of Prmt6 in the skeletal muscle of a mouse model of SBMA 16 .…”