Most attempts at weight loss are frustrated by the body's propensity to maintain fat mass. There are genetic and environmental mechanisms behind this phenomenon, such as thrifty genes, sedentary lifestyle and abundant food resources. We will outline a physiologic mechanism that may perpetuate obesity once it develops. Specifically, we suggest that obesity-induced hyperinsulinemia facilitates fuel storage as fat. This can be exacerbated by high glucocorticoid activity, low growth hormone (GH) activity and the paradoxical increase in free fatty acid (FFA) flux resulting from basal lipolysis in an expanded fat mass. We also outline mechanisms by which obesity may perpetuate low GH and increased glucocorticoid activity in the metabolic syndrome.
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