title: High-fat diet exacerbates renal dysfunction in SHR: reversal by induction of HO-1-adiponectin axis.
abstract: 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.
authors.affiliation: First Geriatric Cardiology Department, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Inoue
authors.forename: Komal
authors.initials: K
authors.lastname: Sodhi
authors.forename: Nitin
authors.initials: N
authors.lastname: Puri
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Peterson
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D018932:Chemokine CCL2 / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D051547:Heme Oxygenase-1 / Q000097:blood / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D009765:Obesity / Q000097:blood*; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D051547:Heme Oxygenase-1