Key Findings:
Spontaneously hypertensive (SHR)/NDmcr-cp rats show many characteristics observed in patients with the metabolic syndrome. Gene expression of PPAR-a, PPAR-g and sterol-regulatory element-binding protein (SREBP)-1c were assessed following with flax oil or lard diets. PPAR-a is known to regulate the expression of genes involved in beta-oxidation of fatty acids and SREBP-1c regulates the expression of genes involved in de novo lipogenesis and fatty acid metabolism. PPAR-g expression has been associated with insulin-sensitising effects. SHR/NDmcr-cp rats fed flax had much lower hepatic concentrations of TAG and cholesterol compared with lard fed rats. A significant reduction in the urinary TBARS levels in the obese SHR/NDmcr-cp rats, a marker for the systemic oxidative stress followed the flax diet. Reductions in plasma insulin concentration in the obese SHR/NDmcr-cp rats were observed after flax oil feeding. An increase in the hepatic mRNA expression of PPAR-gamma by flax oil feeding showed a negative correlation with hepatic lipid levels in the obese SHR/NDmcrcp rats.
ABSTRACT:
Flax oil feeding has been proposed to have beneficial effects on the outcome of the metabolic syndrome due to the high n-3 fatty acid content of flax oil; however, the mechanisms of its action remain largely unknown. We investigated the effects of flax oil feeding on hyperlipidaemia, hyperglycaemia, hepatic steatosis and oxidative stress in the spontaneously hypertensive (SHR)/NDmcr-cp rats, a genetic model of the metabolic syndrome. Hepatic gene expression of PPAR-a, PPAR-g and sterol-regulatory element-binding protein-1c was also assessed in order to investigate the possible underlying mechanisms. Obese and lean SHR/NDmcr-cp rats were fed high-fat diets enriched with either lard or flax oil for a period of 4 weeks. Obese rats exhibited higher body weight, liver weight and mesenteric fat-, epididymal fat- and renal fat-pad weights, and also TAG and cholesterol concentrations in serum and VLDL, LDL and HDL fractions, when compared with the lean rats (P<0.001), irrespective of the diets. Concentrations of fasting serum insulin and urinary thiobarbituric acid reactive substances were lower in flax oil-fed obese (FO) rats compared with the lard-fed obese (LO) rats (P<0.01). Flax oil feeding also revealed a significant reduction in hepatic TAG and cholesterol concentrations in obese rats compared with the LO rats (P<0.05). In addition, FO rats exhibited significantly higher hepatic mRNA expression of PPAR-g, which negatively correlated (r -0.98, P<0.05) with their hepatic lipid levels. These findings suggest that flax oil feeding may activate PPAR-g-dependent pathways to alter the hepatic lipid metabolism and to increase insulin sensitivity in the obese SHR/NDmcr-cp rats. (Author’s Abstract)
Link to Full Text