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Publication
Thrombospondin 1 mediates high-fat diet-induced muscle fibrosis and insulin
resistance in male mice.
Authors Inoue M, Jiang Y, Barnes RH, Tokunaga M, Martinez-Santibañez G, Geletka L,
Lumeng CN, Buchner DA, Chun TH
Submitted By Tae-Hwa Chun on 1/24/2014
Status Published
Journal Endocrinology
Year 2013
Date Published
Volume : Pages 154 : 4548 - 4559
PubMed Reference 24140711
Abstract 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.




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