Cardiovascular disease is associated with high fat diet-induced liver damage and upregulation of hepatic expression of hypoxia-inducible factor 1 alpha in a rat model.

BURGUEÑO A.; FERNÁNDEZ GIANOTTI T.; GONZALES MANSILLA N.; PIROLA C.J.; SOOKOIAN S.

CLINICAL SCIENCE (LONDON, ENGLAND : 1979)

PORTLAND PRESS LTD

Lugar: Londres; Año: 2013 p. 53 - 63

0143-5221

Cardiovascular disease (CVD) is associated with abnormal liver enzymes, and nonalcoholic fatty liver disease (NAFLD) is independently associated with cardiovascular risk. To gain insights into the molecular events underlying the association between liver enzymes and CVD, we developed a high-fat diet (HFD)-induced NAFLD in the spontaneously hypertensive rat (SHR) and its control Wistar-Kyoto (WKY) strain. We hypothesized that hepatic induction of hypoxia-inducible factor 1 alpha (Hif1a) might be the link between CVD and liver injury. Sixteen-week-old male SHR (n=13) and WKY (n=14) rats were divided into two experimental groups: standard chow diet and HFD (10 weeks). Results: HFD-fed rats irrespective of strain developed NAFLD; only HFD-SHR showed focus of lobular inflammation and high levels of hepatic tumor necrosis factor α. SHR rats had significantly higher liver weight, and alanine aminotransferase (ALT) levels, irrespective of NAFLD. Liver abundance of Hif1a mRNA and protein were overexpressed in SHRs (p