Short-term versus long-term effects of adipocyte toll-like receptor 4 activation on insulin resistance in male mice

Caroline Tao, William L. Holland, Qiong A. Wang, Mengle Shao, Lin Jia, Kai Sun, Xiaoli Lin, Yi Chun Kuo, Joshua A. Johnson, Ruth Gordillo, Joel K. Elmquist, Philipp E. Scherer

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Chronic exposure to high-saturated fat diets (HFDs) increases the prevalence of obesity and contributes to the development of low-grade inflammation and insulin resistance.A possiblemediator accounting for obesity-associated inflammation and insulin resistance is Toll-like receptor 4 (TLR4). We investigated the role of adipocyte TLR4 in lipid and glucose homeostasis through an inducible, adipocytespecific deletion of TLR4 in amousemodel that is referred to as the "Tadipo" mouse. Consistent with a critical role for inflammation as a positive force for healthy adipose tissue expansion, chronic HFD exposure results in exacerbatedwhole-body andmuscle insulin resistance in the absence of TLR4 in the adipocyte. Elimination of TLR4 in adipocytes affects TLR4 expression in other tissues,with reduced TLR4 expression in peritoneal macrophages and in the liver. In contrast, TLR4 deletion from adipocytes protects whole-body insulin sensitivity after an acute lipid challenge during a hyperinsulinemic euglycemic clamp. Our results therefore demonstrate dichotomous effects of TLR4 on adipose tissue functionality,with an important positive role of TLR4 during a chronic HFDchallenge due to the lack of adipose tissue remodeling and a negative role of TLR4 as a mediator of insulin resistance in the adipocyte during an acute challenge with saturated fatty acids.

Original languageEnglish (US)
Pages (from-to)1260-1270
Number of pages11
Issue number5
StatePublished - May 1 2017

ASJC Scopus subject areas

  • Endocrinology


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