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Improved insulin sensitivity and reduced adiposity with aP2 driven TLR4 overexpression in transgenic mice
Author(s) -
OnoMoore Kikumi D,
Zhao Ling,
Huang Shurong,
Kim Jeonga,
Rutkowsky Jennifer M,
Snodgrass Ryan G,
Schneider Dina A,
Quon Michael J,
Hwang Daniel H
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1083.6
Subject(s) - insulin resistance , inflammation , tlr4 , endocrinology , medicine , genetically modified mouse , transgene , obesity , insulin receptor , insulin , receptor , diabetes mellitus , biology , chemistry , gene , biochemistry
Chronic low grade inflammation is associated with obesity and diabetes. The underlying causes and mechanisms mediating chronic low grade inflammation in metabolic disorders are not well understood. Toll‐like receptor 4 (TLR4) mediates both infection‐induced and sterile inflammation by recognizing pathogen‐associated molecular patterns (PAMPs) and endogenous molecules, including saturated fatty acids, respectively. It has been shown that saturated fatty acids can activate TLR4 (Lee et al. 2001), and that TLR4 deficient mice were protected from high fat diet (HFD)‐ induced obesity and insulin resistance suggesting that TLR4‐ mediated inflammation may cause insulin resistance (Shi, Kokoeva et al. 2006). Thus, we made transgenic (Tg) mice expressing a constitutively active TLR4 driven by aP2 promoter to determine whether these Tg mice would have increased insulin resistance. Surprisingly, these Tg mice fed a normal chow diet had improved insulin sensitivity with reduction of food intake, adiposity, and body weight gain when compared with wild type littermates. These results raise an important question of whether TLR4‐ mediated inflammation is a direct cause of insulin resistance or promotes secondary changes including adaptive response to reduce energy (food) intake. (USDA‐ARS‐WHNRC Program Funds and NIH‐DK 064007, ADA 1–12‐BS‐99 to J.K).