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Transgenic mice with ectopic expression of constitutively active TLR4 in adipose tissues do not show impaired insulin sensitivity.

Transgenic mice with ectopic expression of constitutively active TLR4 in adipose tissues do not show impaired insulin sensitivity.
Author Information (click to view)

Ono-Moore KD, Zhao L, Huang S, Kim J, Rutkowsky JM, Snodgrass RG, Schneider DA, Quon MJ, Graham JL, Havel PJ, Hwang DH,


Ono-Moore KD, Zhao L, Huang S, Kim J, Rutkowsky JM, Snodgrass RG, Schneider DA, Quon MJ, Graham JL, Havel PJ, Hwang DH, (click to view)

Ono-Moore KD, Zhao L, Huang S, Kim J, Rutkowsky JM, Snodgrass RG, Schneider DA, Quon MJ, Graham JL, Havel PJ, Hwang DH,

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Immunity, inflammation and disease 2017 08 04() doi 10.1002/iid3.162
Abstract
INTRODUCTION
Chronic low-grade inflammation is associated with obesity and diabetes. However, what causes and mediates chronic inflammation in metabolic disorders is not well understood. Toll-like receptor 4 (TLR4) mediates both infection-induced and sterile inflammation by recognizing pathogen-associated molecular patterns and endogenous molecules, respectively. Saturated fatty acids can activate TLR4, and TLR4-deficient mice were protected from high fat diet (HFD)-induced obesity and insulin resistance, suggesting that TLR4-mediated inflammation may cause metabolic dysfunction, such as obesity and insulin resistance.

METHODS
We generated two transgenic (TG) mouse lines expressing a constitutively active TLR4 in adipose tissue and determined whether these TG mice would show increased insulin resistance.

RESULTS
TG mice fed a high fat or a normal chow diet did not exhibit increased insulin resistance compared to their wild-type controls despite increased localized inflammation in white adipose tissue. Furthermore, females of one TG line fed a normal chow diet had improved insulin sensitivity with reduction in both adiposity and body weight when compared with wild-type littermates. There were significant differences between female and male mice in metabolic biomarkers and mRNA expression in proinflammatory genes and negative regulators of TLR4 signaling, regardless of genotype and diet.

CONCLUSIONS
Together, these results suggest that constitutively active TLR4-induced inflammation in white adipose tissue is not sufficient to induce systemic insulin resistance, and that high fat diet-induced insulin resistance may require other signals in addition to TLR4-mediated inflammation.

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