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Mitochondria-Based Model for Fetal Origin of Adult Disease and Insulin Resistance
aDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea bDepartment of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea cDepartment of Biochemistry, Ulsan University College of Medicine, Seoul, Korea
Address for correspondence: Hong Kyu Lee, M.D., Ph.D., Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, Korea. Voice: +82-2-760-2266; fax: +82-2-762-7966. hkleemd{at}snu.ac.kr
Insulin resistance has been recognized as the fundamental underlying metabolic defect in the pathogenesis of metabolic syndrome, a clustering of cardiovascular risk factors such as diabetes, hypertension, dyslipidemia, and obesity. Recent studies established that mitochondrial dysfunction is involved in insulin resistance in general and fetal origin of this state in particular. Because genes are the fundamental molecular basis of inheritance—and thus the cornerstones of evolution—a model explaining insulin resistance is based at the gene level at best. Since a certain mtDNA polymorphism, 16189T>C, is associated with insulin resistance, mtDNA has to be a basic component of the gene-based model. We developed a mitochondria-based model that explains insulin resistance in terms of quantitative and qualitative change of the mitochondrion and its DNA. This model can accommodate several important hypotheses, such as thrifty genotype hypothesis, thrifty phenotype hypothesis, fetal insulin hypothesis, contribution of metabolic imprinting by epigenetic changes, and many other features associated with insulin resistance. We will discuss mechanisms that indicate why the perturbed initial condition of mitochondrial function should lead to the reduced insulin sensitivity.
Key Words: mitochondrial DNA • mitochondrial dysfunction • insulin resistance • fetal malnutrition • thrifty phenotype This article has been cited by other articles:
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