How Strongly Does Appetite Counter Weight Loss? Quantification of the Feedback Control of Human Energy Intake.
To quantify the feedback control of energy intake in response to long-term covert manipulation of energy balance in free-living humans.



A validated mathematical method was used 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. The relationship between the body weight time course and the calculated energy intake changes was analyzed using principles from engineering control theory.



It was discovered that weight loss leads to a proportional increase in appetite resulting in eating above baseline by ∼100 kcal/day per kilogram of lost weight-an amount more than threefold larger than the corresponding energy expenditure adaptations.



While energy expenditure adaptations have often been considered 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.
Janssen Research & Development, LLC, San Diego, California, USA.
David
D
Polidori
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Arjun
A
Sanghvi
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Randy J
RJ
Seeley
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. kevinh@niddk.nih.gov.
Kevin D
KD
Hall
D000328:Adult; D000368:Aged; D001066:Appetite; D015415:Biomarkers; D015992:Body Mass Index; D001835:Body Weight; D000068896:Canagliflozin / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D002149:Energy Intake; D004734:Energy Metabolism; D025461:Feedback, Physiological; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D015203:Reproducibility of Results; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D055105:Waist Circumference; D015431:Weight Loss
D015415:Biomarkers; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin; D005947:Glucose