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An impaired gut immune response to a high-fat diet is associated with visceral adipose inflammation and peripheral insulin resistance in leptin-deficient mice
FASEB Journal (2008)
  • Sin H. Gieng, Children's Hospital Oakland Research Institute
  • Aria Eshraghi, Children's Hospital Oakland Research Institute
  • Elizabeth Hawley, Children's Hospital Oakland Research Institute
  • Patrick Sanger, Children's Hospital Oakland Research Institute
  • Julia Menshenina, Children's Hospital Oakland Research Institute
  • Mark K. Shigenaga, Children’s Hospital Oakland Research Institute
Abstract
The role of leptin as an immune modifier in the gut following standard chow versus high-fat, no-fiber (HF) diet feeding was examined in Ob/Ob and wild-type (WT) mice. Ileum and mesenteric adipose gene expression, cecal digesta bacterial composition, and fasting levels of plasma glucose, insulin, and cholesterol were determined. Inflammatory markers (Saa3, Mcp1, and F4/80) in the ileum increased in response to HF diet in WT but not in Ob/Ob mice. In contrast, these markers in mesenteric adipose increased in Ob/Ob versus WT mice but were not affected by HF diet. Concurrently, total bacteria and Bacteroides decreased and Enterococcus and Lactobacillus increased in response to HF diet in both WT and Ob/Ob mice. However, Enterobacteriaceae increased in response to HF diet in Ob/Ob but not WT mice. Insulin resistance, as measured by HOMA-IR, was higher in Ob/Ob mice in response to HF diet at week 8 and was further, but similarly, elevated in both Ob/Ob diet groups at week 14, a metabolic alteration that we postulate is associated with impaired gut immunity and shifts in gut bacteria. In conclusion, leptin deficiency is associated with an impaired gut immune response to a HF diet and is associated with alterations in gut bacterial composition, an accelerated increase in peripheral insulin resistance, and increased plasma cholesterol. Establishing a mechanistic link between gut immunity and insulin resistance will require experimental manipulation of gut bacteria, a current focus of our ongoing studies. Funded by NIH P60MD00222.
Disciplines
Publication Date
March, 2008
Citation Information
Sin H. Gieng, Aria Eshraghi, Elizabeth Hawley, Patrick Sanger, et al.. "An impaired gut immune response to a high-fat diet is associated with visceral adipose inflammation and peripheral insulin resistance in leptin-deficient mice" FASEB Journal Vol. 22 Iss. 450.1 (2008) ISSN: 0892-6638
Available at: http://works.bepress.com/john-gieng/30/