In　aging　and　metabolic　disease,　sarcopenic　obesity　(SO)　correlates　with　intramuscular　adipose　tissue　(IMAT).　Using　bioinformatics　analysis,　we　found　a　potential　target　protein　Extended　Synaptotagmin　1　(E-syt1)　in　SO.　To　investigate　the　regulatory　role　of　E-syt1　in　muscle　metabolism,　we　performed　in　vivo　and　in　vitro　experiments　through　E-syt1　loss-　and　gain-of-function　on　muscle　physiology.　When　E-syt1　is　overexpressed　in　vitro,　myoblast　proliferation,　differentiation,　mitochondrial　respiration,　biogenesis,　and　mitochondrial　dynamics　are　impaired,　which　were　alleviated　by　the　silence　of　E-syt1.　Furthermore,　overexpression　of　E-syt1　inhibited　mitophagic　flux.　Mechanistically,　E-syt1　overexpression　leads　to　mitochondrial　calcium　overload　and　mitochondrial　ROS　burst,　inhibits　the　fusion　of　mitophagosomes　with　lysosomes,　and　impedes　the　acidification　of　lysosomes.　Animal　experiments　demonstrated　the　inhibition　of　E-syt1　increased　the　capacity　of　endurance　exercise,　muscle　mass,　mitochondrial　function,　and　oxidative　capacity　of　the　muscle　fibers　in　OVX　mice.　These　findings　establish　E-syt1　as　a　novel　contributor　to　the　pathogenesis　of　skeletal　muscle　metabolic　disorders　in　SO.　Consequently,　targeting　E-syt1-induced　dysfunction　may　serve　as　a　viable　strategy　for　attenuating　SO.