{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:42:22Z","timestamp":1793104942248,"version":"4.5.0"},"reference-count":49,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:p>Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing, quantitative PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with a new collagen deposition. At the same time, the Thbs1-null mice display a better circadian rhythm and higher amplitude of energy expenditure with a browning phenotype in sc adipose tissues. These results suggest that THBS1, which circulates in response to a HFD, may induce insulin resistance and fibrotic tissue damage in skeletal muscles as well as the de-browning of sc adipose tissues in the early stages of a HFD challenge. Our study may shed new light on the pathogenic role played by a circulating extracellular matrix protein in the cross talk between adipose tissues and skeletal muscles during obesity progression.<\/jats:p>","DOI":"10.1210\/en.2013-1587","type":"journal-article","created":{"date-parts":[[2013,10,19]],"date-time":"2013-10-19T01:42:56Z","timestamp":1382146976000},"page":"4548-4559","source":"Crossref","is-referenced-by-count":83,"title":["Thrombospondin 1 Mediates High-Fat Diet-Induced Muscle Fibrosis and Insulin Resistance in Male Mice"],"prefix":"10.1210","volume":"154","author":[{"given":"Mayumi","family":"Inoue","sequence":"first","affiliation":[{"name":"Departments of Internal Medicine (M.I., Y.J., R.H.B., M.T., T.-H.C.), University of Michigan, Ann Arbor, Michigan 48109"},{"name":"Departments ofBiointerfaces Institute (M.I., Y.F., R.H.B., T.-H.C.), University of Michigan, Ann Arbor, Michigan 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