Endurance exercise improves age- and obesity-related cardiac dysfunction and locomotor impairment through muscle Gγ1 gene in Drosophila

Abstract

Gγ1, a member of the G protein γ subunit family, participates in regulating diverse physiological processes such as energy metabolism and actomyosin dynamics. However, it remains unclear whether muscle Gγ1 is involved in regulating lipid metabolism and obesity-related complications during the aging process, as well as the effects of exercise intervention on these outcomes. In this study, Gγ1 gene was knocked down and overexpressed in Drosophila muscles using the Gγ1^{UAS-RNAi/Mef2-Gal4} and Gγ1^{UAS-OE/Mef2-Gal4} systems. Following a 4-week endurance exercise regimen. Results showed that muscle-specific knockdown of Gγ1 accelerated age-related lipid accumulation and toxicity, as evidenced by elevated triglyceride and malondialdehyde levels, and induced mitochondrial dysfunction involving suppression of the Sir2/PGC-1α/MRCC-I pathway. These changes were accompanied by aggravated aging-related phenotypes in Drosophila, including declines in motor performance (climbing speed) and cardiac function (heart rate and fractional shortening), as well as a significant reduction in lifespan. Conversely, overexpression of Gγ1 produced opposite effects. Endurance exercise training alleviated obesity-related cardiac dysfunction and locomotor impairment by upregulating muscle Gγ1 expression in aging Drosophila, and this effect resembled an additive enhancement under conditions of muscle-specific Gγ1 overexpression. These findings suggest that muscle Gγ1 may serve as a potential therapeutic target for obesity and aging-related interventions, and exercise represents an effective strategy for mitigating metabolic and aging defects associated with muscle Gγ1 deficiency.

Keywords: Aging; Exercise; Gγ1 gene; Heart; Obesity; Skeletal muscle.