Thromboxane synthase deficiency improves insulin action and attenuates adipose tissue fibrosis

American Journal of Physiology. Endocrinology and Metabolism
Xia LeiG William Wong

Abstract

Thromboxane A2, an arachidonic acid-derived eicosanoid generated by thromboxane synthase (TBXAS), plays critical roles in hemostasis and inflammation. However, the contribution of thromboxane A2 to obesity-linked metabolic dysfunction remains incompletely understood. Here, we used in vitro and mouse models to better define the role of TBXAS in metabolic homeostasis. We found that adipose expression of Tbxas and thromboxane A2 receptor (Tbxa2r) was significantly upregulated in genetic and dietary mouse models of obesity and diabetes. Expression of Tbxas and Tbxa2r was detected in adipose stromal cells, including macrophages. Furthermore, stimulation of macrophages with interferon-γ or resistin factors known to be upregulated in obesity induced Tbxas and Tbxa2r expression. Mice lacking Tbxas had similar weight gain, food intake, and energy expenditure. However, loss of Tbxas markedly enhanced insulin sensitivity in mice fed a low-fat diet. Improvement in glucose homeostasis was correlated with the upregulated expression of multiple secreted metabolic regulators (Ctrp3, Ctrp9, and Ctrp12) in the visceral fat depot. Following a challenge with a high-fat diet, Tbxas deficiency led to attenuated adipose tissue fibrosis and reduced ci...Continue Reading

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Citations

Nov 5, 2016·Progress in Lipid Research·Yang YangWei Yi
Aug 25, 2016·American Journal of Physiology. Endocrinology and Metabolism·Susana RodriguezG William Wong
Feb 23, 2017·American Journal of Physiology. Endocrinology and Metabolism·Pia S PetersenG William Wong
Dec 17, 2015·American Journal of Physiology. Endocrinology and Metabolism·Risa M WolfG William Wong
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Susana RodriguezG William Wong
Jun 3, 2021·Biomolecules·Ke LiYajuan Zheng

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