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Attenuation of obesity, insulin resistance, and inflammation in TLR4 deficient 10ScN mice in response to a diet high in saturated fat
Author(s) -
Davis Jeremy E,
Gabler Nicholas K,
WalkerDaniels Jennifer,
Spurlock Michael E
Publication year - 2007
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.21.5.a378-b
Subject(s) - medicine , endocrinology , insulin resistance , inflammation , insulin , saturated fat , tlr4 , obesity , immune system , immunology , cholesterol
TLR4, a key pattern recognition receptor involved in the innate immune response, is activated by saturated fatty acids (FA). To further investigate the involvement of this receptor in FA induced insulin resistance and inflammation we utilized 10ScN TLR4‐deficient and 10J control mice. Animals were fed low fat (LF), high fat (HF), or high fat palmitate (HFP) diets ad libitum for 16 weeks. At termination, organ weight, serum glucose, insulin, and monocyte chemoattractant protein 1 (MCP1) were evaluated. Body and fat pad weight, glucose, and insulin were lower and glucose: insulin ratio (GIR) were higher in 10ScN compared to 10J mice (P<0.0001). Additionally, there was a 7‐fold higher serum MCP1 concentration in 10J vs. 10ScN mice (P<0.0001). HF diet increased body and fat pad weight, glucose, and GIR (P<0.01). Alternatively, HFP diet increased fat pad weight and serum glucose (P<0.05). Overall, there was a significant genotype by diet interaction on fat pad weight, insulin, and GIR. Specifically, the HFP diet resulted in lower fat pad weights and insulin concentrations (P<0.05), and higher GIR (P<0.01) in 10ScN than in 10J mice. Collectively, these data indicate lower adiposity, improved insulin sensitivity, and reduced markers of inflammation in 10ScN mice. Furthermore, deficiency in TLR4 may specifically attenuate the effects of a diet rich in saturated FA.