Could mitochondrial efficiency explain the susceptibility to adiposity, metabolic syndrome, diabetes and cardiovascular diseases in South Asian populations?

Background: South Asians are susceptible to cardiovascular disease (CVD), especially after migration to affluent countries. Contributing factors include high prevalence of diabetes, and possibly insulin resistance. Excess adiposity centrally may underlie such metabolic disturbances. The thrifty genotype, thrifty phenotype, adipose tissue compartment and variable disease selection hypotheses are among the explanations posed.

Methods: Data from individual studies and review articles known to the authors were examined. A Medline bibliographic database search was also performed. Reference lists were reviewed to identify additional relevant data sources. Key references were examined by both authors.

Results: We propose, and evaluate, the evidence for a 'mitochondrial efficiency hypothesis' i.e. that ancestral changes in mitochondrial coupling efficiency enhanced the successful adaptation of South Asians to environmental stressors by maximizing the conversion of energy to adenosine triphosphate (ATP) rather than heat. This adaptation may be disadvantageous when South Asians are physically inactive and consume high-caloric diets. There is evidence that common mitochondrial mutations vary geographically. Mutations, including those affecting the function of mitochondrial uncoupling proteins (UCPs), may influence the balance of energy and heat production. These may influence basal metabolic rate (BMR), energy efficiency, the tendency to gain weight and hence metabolic disease. UCP gene polymorphisms are related to differences in BMR between African-Americans and Europeans. Similar data for South Asians are lacking but the few studies comparing BMR indicate that South Asians have a lower BMR, which is explained by a lower lean body mass, and higher fat mass. Once adjusted for body composition, BMR is similar. A high fat mass, per se, is a strategy for reducing energy use while conserving body size. Indians in the USA had higher oxidative phosphorylation capacity than Northern European Americans.

Conclusion: The evidence justifies full exploration of this mitochondrial efficiency hypothesis in South Asians, which may also be relevant to other warm-climate adapted populations.