Abstract
Atg2 plays a vital role in regulating the ageing process. Autophagy and lysosomal repair depend on the lipid transport function of Atg2. The molecular mechanisms of the muscle Atg2 gene resistance to high-fat diet (HFD)-induced age-related damages of skeletal muscle are not known. In this study, we achieved overexpression and knockdown of the muscle Atg2 gene in drosophila by constructing the Atg2[UAS]/Mhc[Gal4] system. Drosophila was subjected to an HFD intervention for three weeks. The findings demonstrated that an HFD markedly reduced climbing endurance and speed, down-regulated muscle Atg2, Atg8a (a mammalian ortholog of LC3 and an autophagy marker), ATGL, Sirt1, and PGC-1α gene expression, and raised MDA and TG in elderly drosophila. Age-related muscle degeneration caused by a high-fat diet was worsened by knocking down muscle Atg2. In contrast, age-related muscle degeneration brought on by a high-fat diet was avoided by overexpressing the Atg2 gene in muscles. Therefore, the present findings demonstrated that the muscle Atg2 gene was essential for skeletal muscle resistance against age-related damages caused by a high-fat diet by controlling the activity of the ATGL/Sirt1/PGC-1α pathway, oxidative balance, and lipid metabolism.
