4.6 Article

Ablation of Ghrelin Receptor Mitigates the Metabolic Decline of Aging Skeletal Muscle

期刊

GENES
卷 13, 期 8, 页码 -

出版社

MDPI
DOI: 10.3390/genes13081368

关键词

GHS-R; aging; irisin; skeletal muscle

资金

  1. American Diabetes Association [1-15-BS-177]
  2. NIH [R01DK118334, R01AG064869, P30 ES029067]
  3. BrightFocus Foundation [A2019630S]
  4. USDA Hatch project [1010840]
  5. Multistate project [NE1939]

向作者/读者索取更多资源

The hormone ghrelin has various effects on the health and disease, and its receptor, growth hormone secretagogue receptor (GHS-R), plays a role in the metabolic dysfunction of aging adipose tissues. This study explores the impact of GHS-R on the metabolic functions of aging skeletal muscle and its potential regulation through the myokine irisin.
The orexigenic hormone ghrelin has multifaceted roles in health and disease. We have reported that ablation of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), protects against metabolic dysfunction of adipose tissues in aging. Our further observation interestingly revealed that GHS-R deficiency phenocopies the effects of myokine irisin. In this study, we aim to determine whether GHS-R affects the metabolic functions of aging skeletal muscle and whether GHS-R regulates the muscular functions via irisin. We first studied the expression of metabolic signature genes in gastrocnemius muscle of young, middle-aged and old mice. Then, old GHS-R knockout (Ghsr(-/-)) mice and their wild type counterparts were used to assess the impact of GHS-R ablation on the metabolic characteristics of gastrocnemius and soleus muscle. There was an increase of GHS-R expression in skeletal muscle during aging, inversely correlated with the decline of metabolic functions. Remarkedly the muscle of old GHS-R knockout (Ghsr(-/-)) mice exhibited a youthful metabolic profile and better maintenance of oxidative type 2 muscle fibers. Furthermore, old Ghsr(-/-) mice showed improved treadmill performance, supporting better functionality. Also intriguing to note was the fact that old GHS-R-ablated mice showed increased expression of the irisin precursor FNDC5 in the muscle and elevated plasma irisin levels in circulation, which supports a potential interrelationship between GHS-R and irisin. Overall, our work suggests that GHS-R has deleterious effects on the metabolism of aging muscle, which may be at least partially mediated by myokine irisin.

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