Metabolic Responses to Weight Perturbation
The increasing prevalence of overweight and obesity is the cause of some of the largest and most costly current health care problems in the United States. This epidemic of obesity and its co-morbidities reflects the interaction of alleles of genes that favor the storage of excess calories as fat with an environment that provides ad libitum availability of calorically dense foods and encourages sedentary lifestyles. Almost anyone who has ever lost weight can attest to the observation that it is harder to sustain weight loss than to lose weight. The over 80% recidivism rate to pre-weight loss levels of body fatness after otherwise successful weight loss is due to the coordinate actions of metabolic, behavioral, neuroendocrine, and autonomic responses designed to keep body energy stores (fat) above a CNS-defined minimum. Much of this opposition to sustained weight loss is mediated by the adipocyte-derived hormone, leptin.
KeywordsReduced Body Weight Negative Energy Balance Daily Energy Expenditure Sedentary Individual Follow Weight Loss
A large number of indispensable collaborators have contributed significantly to the work presented in this manuscript. These collaborators include Drs. Jules Hirsch, Louis Aronne and Karen Segal and the nursing and nutritional staffs at Rockefeller University Hospital; Drs. Krista Vandenborne and Jack Leigh at the University of Pennsylvania Medical Center; and Drs. Daniel Bloomfield, Dympna Gallagher, Rochelle Goldsmith, Steven Heymsfield, Joy Hirsch, Anthony Magnano, Laurel Mayer, Louis Weimer, and Richard Smiley and the nursing and nutritional staffs at the Irving Center for Clinical and Translational Research at Columbia University Medical Center. Recombinant human leptin for our studies has been provided by Amgen, Inc. (Thousand Oaks California) and Amylin Pharmaceuticals Inc. (San Diego, CA).These studies were supported in part by NIH Grants # DK30583, DK37948, DK64773, DKP30 26687, RR00102, RR00645, and RR024156.
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