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Short-Term Versus Long-Term Effects of Adipocyte Toll-Like Receptor 4 Activation on Insulin Resistance in Male Mice.

Endocrinology | May 1, 2017

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 possible mediator 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, adipocyte-specific deletion of TLR4 in a mouse model 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 exacerbated whole-body and muscle 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 HFD challenge 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.

Pubmed ID: 28323977 RIS Download

Mesh terms: Adipocytes | Adipocytes, Brown | Adipose Tissue | Animals | Diet, High-Fat | Dietary Fats | Insulin Resistance | Liver | Male | Mice | Mice, Knockout | Time Factors | Toll-Like Receptor 4

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Associated grants

  • Agency: NIDDK NIH HHS, Id: P01 DK088761
  • Agency: NIA NIH HHS, Id: P01 AG051459
  • Agency: NCI NIH HHS, Id: P30 CA142543
  • Agency: NIDDK NIH HHS, Id: F30 DK108534
  • Agency: NIDDK NIH HHS, Id: K01 DK107788
  • Agency: NIDDK NIH HHS, Id: R01 DK099110
  • Agency: NIDDK NIH HHS, Id: R01 DK055758

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