How strongly does appetite counter weight loss? Quantification of the homeostatic control of human energy intake
ObjectiveTo quantify the homeostatic feedback control of energy intake in response to long-term covert manipulation of energy balance in free-living humans.\n\nMethodsWe used a validated mathematical method to calculate energy intake changes during a 52 week placebo-controlled trial in 153 patients treated with canagliflozin, a sodium glucose co-transporter inhibitor that increases urinary glucose excretion thereby resulting in weight loss without patients being directly aware of the energy deficit. We analyzed the relationship between the body weight time course and the calculated energy intake changes using principles from engineering control theory.\n\nResultsWe discovered that weight loss leads to a proportional homeostatic drive to increase energy intake above baseline by ~100 kcal/day per kg of lost weight - an amount more than 3-fold larger than the corresponding energy expenditure adaptations.\n\nConclusionsWhile energy expenditure adaptations are often thought to be the main reason for slowing of weight loss and subsequent regain, feedback control of energy intake plays an even larger role and helps explain why long-term maintenance of a reduced body weight is so difficult.\n\nFundingThis research was supported by the Intramural Research Program of the NIH, National Institute of Diabetes & Digestive & Kidney Diseases, using data from a study sponsored by Janssen Research & Development, LLC.\n\nDisclosureD.P. is a full-time employee of Janssen Research & Development, LLC. K.D.H. reports patent pending on a method of personalized dynamic feedback control of body weight (US Patent Application No. 13/754,058; assigned to the NIH) and has received funding from the Nutrition Science Initiative to investigate the effects of ketogenic diets on human energy expenditure. R.S. is a paid consultant for Janssen, Novo Nordisk, Takeda, Daichii Sankyo, Novartis, Pfizer, Nestle, Circuit Therapeutics and Ethicon. R.S., also has received research support from Novo Nordisk, Ethicon, Sanofiand Boehringer Ingelheim. A.S. reports no conflicts of interest.\n\nWhat is already known about this subject?O_LIHuman body weight is believed to be regulated by homeostatic feedback control of both energy intake and energy expenditure.\nC_LIO_LIAdaptations of energy expenditure to weight loss have been well-established, but the homeostatic control of energy intake has yet to be quantified.\nC_LI\n\nWhat this study addsO_LIWe provide the first quantification of the homeostatic control of energy intake in free-living humans.\nC_LIO_LIThe increase in energy intake per kg of weight lost is several-fold larger than the known energy expenditure adaptations.\nC_LIO_LIHomeostatic control of energy intake is likely the primary reason why it is difficult to achieve and sustain large weight losses.\nC_LI