Evidence that the mitochondrial genome is the thrifty genome

Although mitochondrial DNA (mtDNA) abnormalities are known to cause insulin deficiency, insulin resistance and diabetes mellitus, it's quantitative aspect was not addressed well. In this review, mitochondrial genome hypothesis of thrifty phenomenon is proposed, based on the data and review of literatures. From a population based epidemiologic study, it was found that mtDNA quantity was decreased in the peripheral blood of diabetic subjects, and also in those subjects who will convert to diabetes mellitus within 2 years. In this population, low mtDNA subjects were found to have higher blood pressure and high waist hip ratio. These findings suggested mtDNA status might be quantitatively linked to the insulin resistance syndrome. As quantitative relationships between peripheral blood mtDNA levels and insulin requirement, and energy utilization pattern (fat and carbohydrate oxidation during hyperinsulinemic clamp studies) were observed in a group of male students; and maternal mtDNA content (peripheral blood) correlated with birth weight and peripheral blood mtDNA content of the offspring in another study, possibility of thrifty phenotype phenomena might be due to the low mitochondrial status arose. As thrifty phenotype phenomenon shows the quantitatively continuous relationship between involved parameters and characteristics of 'imprinting', a possible mechanism is suggested. (C) 1999 Elsevier Science Ireland Ltd. Al rights reserved.