Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808
Address all correspondence and requests for reprints to: George A. Bray, M.D., 6400 Perkins Road, Baton Rouge, Louisiana 70808. E-mail: brayga{at}pbrc.edu.
Obesity is an epidemic disease that threatens to inundate healthcare resources by increasing the incidence of diabetes, heartdisease, hypertension, and cancer. These effects of obesityresult from two factors: the increased mass of adipose tissueand the increased secretion of pathogenetic products from enlargedfat cells. This concept of the pathogenesis of obesity as adisease allows an easy division of disadvantages of obesityinto those produced by the mass of fat and those produced bythe metabolic effects of fat cells. In the former category arethe social disabilities resulting from the stigma associatedwith obesity, sleep apnea that results in part from increasedparapharyngeal fat deposits, and osteoarthritis resulting fromthe wear and tear on joints from carrying an increased massof fat. The second category includes the metabolic factors associatedwith distant effects of products released from enlarged fatcells. The insulin-resistant state that is so common in obesityprobably reflects the effects of increased release of fattyacids from fat cells that are then stored in the liver or muscle.When the secretory capacity of the pancreas is overwhelmed bybattling insulin resistance, diabetes develops. The strong associationof increased fat, especially visceral fat, with diabetes makesthis consequence particularly ominous for health care costs.The release of cytokines, particularly IL-6, from the fat cellmay stimulate the proinflammatory state that characterizes obesity.The increased secretion of prothrombin activator inhibitor-1from fat cells may play a role in the procoagulant state ofobesity and, along with changes in endothelial function, maybe responsible for the increased risk of cardiovascular diseaseand hypertension. For cancer, the production of estrogens bythe enlarged stromal mass plays a role in the risk for breastcancer. Increased cytokine release may play a role in otherforms of proliferative growth. The combined effect of thesepathogenetic consequences of increased fat stores is an increasedrisk of shortened life expectancy.
Abbreviations: apo, Apolipoprotein; BMI, body mass index; CHD,coronary heart disease; HDL, high-density lipoprotein; LDL,low-density lipoprotein; NAFLD, nonalcoholic fatty liver disease;VLDL, very LDL.
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