Sirtuin-1 mediates the obesity induced risk of common degenerative diseases: Alzheimer’s disease, coronary artery disease and type 2 diabetes

Abstract

Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contrib-ute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer's disease (AD). The rise in overweight and obesity in all societies is prompting intense research into the causes and effects of the condition. Obesity disrupts many body systems including glucose and lipid me-tabolism, circadian rhythms and liver function. It also causes or increases inflammation and oxi-dative stress. Within cells, the endoplasmic re-ticulum (ER) appears to be particularly suscep-tible to such metabolic disruption. Sirtuin 1 (Sirt1) and leptin have received attention recently as they are central regulatory factors for the body's metabolic pathways which interact at particular levels, for example lipid and Abeta metabolism. This mini-review discusses recent findings con-cerning obesity, lipid metabolism and the role of Sirtuin 1 and how all influence the ER. A greater understanding of obesity and its effects on me-tabolic control systems of the body are required, to develop pharmacological, dietary and lifestyle changes that will reduce the incidence of CAD, Type 2 diabetes and AD.