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High fat diet induces insulin resistance and heightened renal inflammation in angiotensin II hypertensive rats
Author(s) -
Quigley Jeffrey E.,
Elmarakby Ahmed A.,
Imig John D.
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.a504-c
Subject(s) - medicine , endocrinology , insulin resistance , inflammation , metabolic syndrome , angiotensin ii , chemokine , immune system , downregulation and upregulation , kidney , insulin , receptor , diabetes mellitus , biology , immunology , biochemistry , gene
A major risk factor for renal failure is metabolic syndrome, a disease involving hypertension, obesity, and insulin resistance, with inflammation as part of its etiology. Chronic feeding of a high fat diet has been shown to increase weight gain in rats. We hypothesized that angiotensin II hypertensive rats fed a high fat diet, with metabolic syndrome‐like features, would have increased renal inflammation. In the present study, high fat diet fed hypertensive rats were found to be insulin resistant as assessed by euglycemic clamp; they require a lower rate of glucose infusion than hypertensive rats fed a normal diet (7.72±1.8 vs. 21.6±0.8 mg/kg/min). Using real‐time PCR arrays we profiled the expression of inflammatory cytokines/receptors and the NFκB pathway in the kidney cortex. Out of 160 inflammatory genes profiled, 46 were upregulated at least 2‐fold in the high fat diet hypertensive group and 11 genes were downregulated. Among those upregulated were the immune modulators lymphotoxin‐α (61‐fold), IL‐3 (54‐fold), IL‐13 (7.3‐fold), and colony stimulating factor‐3 (21‐fold). Expression of at least 10 chemokine ligands and receptors for various immune cell types also increased. These data suggest that obesity, hypertension, and insulin resistance together elicit an enhanced inflammatory state and diverse immune cell response in the kidney which may contribute to the development of renal damage.