Lycopene ameliorates hyperlipidemia via potentiation of AMP-activated protein kinase and inhibition of ATP-citrate lyase in diabetic hyperlipidemic rat model.

Aim: The present study aimed mainly to demonstrate the metabolic effects of lycopene (LYC) or atorvastatin (ATOR) in diabetic hyperlipidemic rat model.

Main Methods: Rats were randomly classified into four groups; the first was fed normal chow diet (NC) while the other three groups received streptozotocin (STZ) along with CCT-diet. The second group received no treatment (diabetic hyperlipidemic control, DHC), the third one received ATOR (50 mg/kg/day) while the fourth one received LYC (20 mg/kg/day). Serum and tissue samples were collected for biochemical and histological evaluations.

Key Findings: DHC rats demonstrated significant hyperglycemia, dyslipidemia, increased hepatic fatty acid synthetase (FAS), malondialdehyde (MDA), tumor necrosis factor- alpha (TNF-α), 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase and ATP citrate lyase (ACLY). However, hepatic reduced glutathione (GSH) and phosphorylated form of AMP-activated protein kinase (AMPK-P) activities showed significant decreases. ATOR or LYC administration induced hypoglycemic and hypolipidemic effects; decreased hepatic levels of MDA, TNF-α, HMG-CoA reductase, ACLY and FAS along with GSH and AMPK-P increases. Histopathological findings showed clear correlation with the biomarkers results.

Significance: LYC demonstrated favorable significant effects regarding the biomarkers studied as compared to ATOR and may be expressed as a potent therapeutic agent of natural origin for hyperlipidemia complications either alone or in combination with other hypolipidemic drugs.