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High-Fat Diet Exacerbates Renal Dysfunction in SHR: Reversal by Induction of HO-1–Adiponectin Axis
Biochemistry and Microbiology
  • Jian Cao
  • Kazuyoshi Inoue
  • Komal Sodhi, Marshall University
  • Nitin Puri
  • Stephen J. Peterson
  • Rita Rezzani
  • Nader G. Abraham, Marshall University
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High-dietary fat intake is a major risk factor for development of metabolic and cardiovascular-renal dysfunction including obesity, coronary artery disease, hypertension, and chronic renal failure. We examined the effect of a high-fat diet on renal function and morphology in spontaneously hypertensive rats (SHR), a phenotype designed to mimic metabolic syndrome. High-fat diet induced increase (P < 0.05) in blood pressure, body weight, and renal lipid deposition in these rats. This increase in body weight was accompanied by elevations (P < 0.05) of blood glucose and low-density lipoprotein (LDL) levels, a decrease (P < 0.05) in adiponectin and increases (P < 0.05) in plasma monocyte chemotactic protein-1 (MCP-1) along with renal macrophage infiltration. These pathophysiological perturbations were attenuated (P < 0.05) by heme oxygenase-1 (HO-1) induction by treatment with cobalt protoporphyrin (CoPP). Further effects of CoPP included increased (P < 0.05) renal expression of adiponectin along with enhancement (P < 0.05) of pAKT, pAMPK, and p-eNOS in SHRs fed a high-fat diet. Prevention of such beneficial effects of CoPP by the concurrent administration of the heme-HO inhibitor stannous mesoporphyrin (SnMP) corroborates the role of HO system in mediating such effects. Taken together, our results demonstrate that high-fat diet induces a metabolic syndrome-like phenotype in hypertensive rats, which is amenable to rescue by increases in HO-1- and adiponectin-dependent pathways.

The version of record is available from the publisher at Copyright © 2012 North American Association for the Study of Obesity (NAASO)

doi: 10.1038/0by.2011.265

Citation Information
Cao J, Inoue K, Sodhi K, Puri N, Peterson SJ, Rezzani R, Abraham NG. High‐fat diet exacerbates renal dysfunction in SHR: reversal by induction of HO-1-adiponectin Axis. Obesity. 2012;20(5):945-53.