Congenital and Environmental Factors Associated with Adipocyte Dysregulation as Defects of Insulin Resistance
Chao-Ping Wang , Fu-Mei ChungDivision of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 82445 Taiwan.
Shyi-Jang ShinDepartment of Internal Medicine, Kaohsiung Medical University, Kaohsiung, 80307 Taiwan.
Yau-Jiunn LeeLee’s Endocrinologic Clinic, 130 MinTzu Rd., Pingtung, 90000 Taiwan.
The metabolic syndrome refers to insulin resistance and its associated cluster of related cardiovascular metabolic risk factors including type 2 diabetes, hypertension, dyslipidemia and central obesity. Although many hypotheses and facts have been proposed to explain the interaction between genetic and environmental causes of this syndrome, the primary etiology of the metabolic syndrome is adipose tissue dysregulation. Firstly, the thrifty genotype and phenotype hypothesis may explain the endemic increase in type 2 diabetes and cardiovascular disease in developing countries and may elucidate congenital susceptibility to and environmental triggering of the metabolic syndrome. Secondly, overnutrition leads to fatty acid (FA) accumulation in adipocytes and to an overflow to ectopic fat storage organs. This causes functional changes in adipocytes shifting the intra-cellular metabolic pathway toward insulin resistance. Thirdly, obese subjects exhibit increased fat cell size and over-secretion of biologic adipocytokines. Fourthly, failure to adequately develop adipose tissue mass, as seen in lipodystrophy cases, causes severe insulin resistance and diabetes. Lastly, similarly to human type 2 diabetes, Psammonys obesus, a desert rat which feeds mainly on low-calorie vegetation, develops the metabolic syndrome when given a diet of calorie-rich food. The above evidence indicates that adipocyte dysregulation and secretion of FA as well as certain molecules from overloaded adipocytes-adipokines contribute to the pathogenesis of impaired insulin secretion and insulin resistance, endothelial dysfunction, a pro-inflammatory state and promote progression of atherosclerosis. The metabolic syndrome is a modern disease resulting in adipocyte dysmetabolism which originates from the paradox of slow human evolution combined with rapid environmental changes.
Keywordsdiabetes · insulin resistance · metabolic syndrome · adipocyte dysregulation,.
Rev Diabet Stud