THE EFFECTS OF MODERATE CALORIE RESTRICTION AND AGING ON HEPATIC AND CIRCULATING LIPID CONTENT IN MICE

Abstract

Hepatic lipid accumulation increases risk of non-alcoholic fatty liver disease (NAFLD) and contributes to insulin and glucagon resistance. Elevated circulating triglycerides and free fatty acids are associated with atherosclerosis, diabetes, and hypertension. As metabolic diseases have become increasingly prevalent in our population, it is necessary for us to understand the mechanisms behind such diseases and find attainable interventions and treatments. Prolonged calorie restriction (CR) delays the onset of aging, extends lifespan, and improves metabolic function in a variety of animal models. However, many calorie restriction studies utilize a degree of calorie restriction of 30% - 40%, which is not a feasible lifestyle intervention for humans. As such, we investigated moderate (15%) calorie restriction-mediated and aging-mediated changes in hepatic and serum triglyceride (TAG) and non-esterified fatty acid (NEFA) concentrations in mice. Compared to mice fed ad libitum (AL), we found that 15% calorie restriction reduced hepatic TAG concentration in 10 and 18 month old mice, reduced hepatic NEFA concentration in 18 month old mice, and had no effect on serum TAG or NEFA concentrations in any age groups. Interestingly, in AL mice hepatic lipid content appears to decrease from 18 months of age to ~2 years of age. Our data suggest that moderate and prolonged calorie restriction protects against hepatic lipid accumulation in middle-aged mice, but as these mice age, hepatic lipids are not significantly different between diets. This relatively moderate degree of calorie restriction may be an attainable and promising lifestyle intervention for humans.