Middle-aged overweight South Asian men exhibit a different metabolic adaptation to short-term energy restriction compared with Europeans.

AIMS/HYPOTHESIS: South Asians have a higher risk of developing type 2 diabetes than Europeans. The underlying cause of this excess risk is still poorly understood but might be related to differences in the regulation of energy/nutrient-sensing pathways in metabolic tissues and subsequent changes in whole-body substrate metabolism. In this study, we investigated the whole-body and skeletal muscle metabolic adaptations to short-term energy restriction in South Asian and European volunteers. METHODS: Twenty-four middle-aged overweight South Asian and European men underwent a two-step hyperinsulinaemic-euglycaemic clamp, with skeletal muscle biopsies and indirect calorimetry before and after an 8 day diet very low in energy (very low calorie diet [VLCD]). Abdominal fat distribution and hepatic triacylglycerol content were assessed using MRI and MR spectroscopy. RESULTS: South Asian men had higher hepatic triacylglycerol content than European men, and exhibited elevated clamp insulin levels that probably reflect a lower insulin clearance rate. Despite higher insulin levels, endogenous glucose production rate was similar and glucose disposal rate (Rd) and nonoxidative glucose disposal rate (NOGD) were significantly lower in South Asian than European men, indicating impaired whole-body insulin sensitivity. Energy restriction decreased abdominal fat mass and hepatic triacylglycerol content in both groups. However, the shift induced by energy restriction from glucose towards lipid oxidation observed in European men was impaired in South Asian men, indicating whole-body metabolic inflexibility. Remarkably, although energy restriction improved hepatic insulin sensitivity in both groups, Rd improved only in South Asian men owing to higher NOGD. At the molecular level, an increase in insulin-induced activation of the skeletal muscle mTOR pathway was found in South Asian men, showing that skeletal muscle energy/nutrient-sensing pathways were differentially affected by energy restriction. CONCLUSIONS/INTERPRETATION: We conclude that South Asian men exhibit a different metabolic adaptation to short-term energy restriction than European men. TRIAL REGISTRATION: Dutch trial registry ( www.trialregister.nl ), trial number NTR 2473.

Longevity, aging, and caloric restriction: Clive Maine McCay and the construction of a multidisciplinary research program.

Since the 1930s scientists from fields such as biochemistry, pathology, immunology, genetics, neuroscience, and nutrition have studied the relation of dietary caloric intake to longevity and aging. This paper discusses how Clive Maine McCay, a professor of animal husbandry at Cornell University, began his investigation of the topic and promoted it as a productive research program in the multidisciplinary science of gerontology. Initially, McCay observed the effect of reduced-calorie diets on life span and senescence while pursuing his nutrition research in the context of animal husbandry and agriculture. But when he received funding from the Rockefeller Foundation and started to participate in the establishment of gerontology during the 1930s, the scope of his research was considerably expanded beyond his original disciplinary domain. It became a multidisciplinary research program that attracted scholars from a variety of scientific and medical disciplines. This paper argues that through this expansion McCay's research created a means of maintaining cooperation among the diverse and heterogeneous academic fields constituting gerontology.