Lipotoxic and inflammatory phenotypes in rats with uncontrolled metabolic syndrome and nephropathy

Jesus H. Dominguez, Pengfei Wu, C. Subah Packer, Constance Temm, Katherine J. Kelly

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Anomalous inflammatory responses triggered by the metabolic syndrome cause renal injury. This discovery links renal lipid accumulation with lipotoxicity to inflammation and may explain the insidious fibrosis and cellular decay characteristic of nephropathy in the metabolic syndrome. However, it is not clear whether control of inflammation protects the kidney independently of lipid accumulation, which is a required step for lipotoxicity in hyperglycemia and dyslipidemia. We hypothesized that in rats with the metabolic syndrome, and overt nephropathy, treatment with mycophenolate mofetil (MMF; 10 mg·kg-1 ·day-1 ip for 14 wk) would reduce the abnormal renal lipid depots and limit renal inflammation and injury. We studied groups of lean and obese F1 hybrid Zucker fatty diabetic/spontaneous hypertensive heart failure (ZS) rats. MMF did not affect lean rats. In obese ZS rats, MMF did not change severe hyperglycemia or the higher kidney loads of unutilized lipid and peroxidation products. Nonetheless, MMF dramatically reduced diabetes/obesity-derived systemic and renal inflammation, limited renal size, hyperfiltration, and fibrosis. These data indicate that in rats, anti-inflammatory therapy presumably acting downstream, and independently of lipotoxicity, can effectively limit renal injury and fibrosis.

Original languageEnglish (US)
Pages (from-to)F670-F679
JournalAmerican Journal of Physiology - Renal Physiology
Volume293
Issue number3
DOIs
StatePublished - Sep 1 2007

    Fingerprint

Keywords

  • Diabetic nephropathies
  • Lipid peroxidation

ASJC Scopus subject areas

  • Physiology

Cite this