Effects of Chronic Calorie Restriction or Dietary Resveratrol Supplementation on Insulin Sensitivity Markers in a Primate, Microcebus murinus

The prevalence of diabetes and hyperinsulinemia increases with age, inducing metabolic failure and limiting lifespan. Calorie restriction (CR) without malnutrition delays the aging process, but its long-term application to humans seems difficult. Resveratrol (RSV), a dietary polyphenol, appears to be a promising CR mimetic that can be easily administered in humans. In this work, we hypothesized that both CR and RSV impact insulin sensitivity in a non-human primate compared to standard-fed control (CTL) animals. Four- to five-year-old male grey mouse lemurs (Microcebus murinus) were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200 mg·day−1·kg−1). Insulin sensitivity and glycemia were assessed using an oral glucose tolerance test (OGTT) and the homeostasis model assessment of insulin resistance (HOMA-IR index) evaluation after 21 or 33 months of chronic treatment. Resting metabolic rate was also measured to assess the potential relationships between this energy expenditure parameter and insulin sensitivity markers. No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals. After 33 months, CR and RSV decreased glycemia after the oral glucose loading without decreasing fasting blood insulin. A general effect of treatment was observed on the HOMA-IR index, with an 81% reduction in CR animals and 53% in RSV animals after 33 months of treatment compared to CTL. Chronic CR and dietary supplementation with RSV affected insulin sensitivity by improving the glucose tolerance of animals without disturbing their baseline insulin secretion. These results suggest that both CR and RSV have beneficial effects on metabolic alterations, although these effects are different in amplitude between the two anti-aging treatments and potentially rely on different metabolic changes

Low-carbohydrate diets: nutritional and physiological aspects

Recently, diets low in carbohydrate content have become a matter of international attention because of the WHO recommendations to reduce the overall consumption of sugars and rapidly digestible starches. One of the common metabolic changes assumed to take place when a person follows a low-carbohydrate diet is ketosis. Low-carbohydrate intakes result in a reduction of the circulating insulin level, which promotes high level of circulating fatty acids, used for oxidation and production of ketone bodies. It is assumed that when carbohydrate availability is reduced in short term to a significant amount, the body will be stimulated to maximize fat oxidation for energy needs. The currently available scientific literature shows that low-carbohydrate diets acutely induce a number of favourable effects, such as a rapid weight loss, decrease of fasting glucose and insulin levels, reduction of circulating triglyceride levels and improvement of blood pressure. On the other hand some less desirable immediate effects such as enhanced lean body mass loss, increased urinary calcium loss, increased plasma homocysteine levels, increased low-density lipoprotein-cholesterol have been reported. The long-term effect of the combination of these changes is at present not known. The role of prolonged elevated fat consumption along with low-carbohydrate diets should be addressed. However, these undesirable effects may be counteracted with consumption of a low-carbohydrate, high-protein, low-fat diet, because this type of diet has been shown to induce favourable effects on feelings of satiety and hunger, help preserve lean body mass, effectively reduce fat mass and beneficially impact on insulin sensitivity and on blood lipid status while supplying sufficient calcium for bone mass maintenance. The latter findings support the need to do more research on this type of hypocaloric low-carbohydrate diet