SIRTUIN 1 REGULATES AMYLOID BETA OLIGOMER METABOLISM IN HEP G2 CELLS WITH RELEVANCE TO DIET AND ALZHEIMER'S DISEASE

In global communities non alcoholic fatty liver disease (NAFLD), the metabolic syndrome and Alzheimer’s disease (AD) have increased with NAFLD associated with approx..30% of the global population. Monitoring dietary fat intake to reduce NAFLD and amyloidosis has become important to neurodegenerative diseases. Nutritional diets that reduce fat are also involved in the reduction of plasma endotoxins such as lipopolysaccarides (LPS) released from gram-negative bacteria in the intestine. LPS alter hepatic lipid metabolism with an increase in hepatic cytokines and acute phase proteins (APP) in plasma. LPS has also been shown to effect liver cholesterol homeostasis by the modulation of the nuclear receptor Sirtuin 1 (Sirt 1) with effects on amyloid beta (Aβ) metabolism. In experiments with Hep G2 cells Sirt 1 activity was inhibited with the drug Sirtinol with a marked reduction in Aβ clearance in these cells. Suramin an anti-cancer drug (highly charged) was associated with rapid clearance of Aβ in Hep G2 cells. Incubations with fatty acids in fetal bovine serum that contain LPS was associated with Hep G2 steatosis and disturbed Aβ metabolism. Nutritional therapy that involve Sirt 1 activation by low fat high fibre diets reduce LPS levels and prevent NAFLD and AD in global populations.