Energy expenditure in the etiology of human obesity: spendthrift and thrifty metabolic phenotypes and energy-sensing mechanisms
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The pathogenesis of human obesity is the result of dysregulation of the reciprocal relationship between food intake and energy expenditure (EE), which influences daily energy balance and ultimately leads to weight gain. According to principles of energy homeostasis, a relatively lower EE in a setting of energy balance may lead to weight gain; however, results from different study groups are contradictory and indicate a complex interaction between EE and food intake which may differentially influence weight change in humans. Recently, studies evaluating the adaptive response of one component to perturbations of the other component of energy balance have revealed both the existence of differing metabolic phenotypes (“spendthrift” and “thrifty”) resulting from overeating or underfeeding, as well as energy-sensing mechanisms linking EE to food intake, which might explain the propensity of an individual to weight gain. The purpose of this review is to debate the role that human EE plays on body weight regulation and to discuss the physiologic mechanisms linking EE and food intake. An increased understanding of the complex interplay between human metabolism and food consumption may provide insight into pathophysiologic mechanisms underlying weight gain, which may eventually lead to prevention and better treatment of human obesity.
KeywordsEnergy expenditure Adaptive thermogenesis Body weight regulation Metabolic phenotypes Energy sensing
Studies #NCT00523627, #NCT00687115 and #NCT00342732 were supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The protocols were approved by the Institutional Review Board of the National Institute of Diabetes and Digestive and Kidney Diseases.
All volunteers were fully informed of the nature and purpose of the studies (#NCT00523627, #NCT00687115 and #NCT00342732), and written informed consent was obtained.
- 5.Lam YY, Redman LM, Smith SR, Bray GA, Greenway FL, Johannsen D, Ravussin E (2014) Determinants of sedentary 24-h energy expenditure: equations for energy prescription and adjustment in a respiratory chamber. Am J Clin Nutr 99(4):834–842. doi:10.3945/ajcn.113.079566 PubMedPubMedCentralCrossRefGoogle Scholar
- 12.Piaggi P, Masindova I, Muller YL, Mercader J, Wiessner GB, Chen P, Consortium STD, Kobes S, Hsueh WC, Mongalo M, Knowler WC, Krakoff J, Hanson RL, Bogardus C, Baier LJ (2017) A genome-wide association study using a custom genotyping array identifies variants in GPR158 associated with reduced energy expenditure in American Indians. Diabetes. doi:10.2337/db16-1565 Google Scholar
- 20.Weinsier RL, Nelson KM, Hensrud DD, Darnell BE, Hunter GR, Schutz Y (1995) Metabolic predictors of obesity. Contribution of resting energy expenditure, thermic effect of food, and fuel utilization to 4-year weight gain of post-obese and never-obese women. J Clin Investig 95(3):980–985. doi:10.1172/JCI117807 PubMedPubMedCentralCrossRefGoogle Scholar
- 26.Thearle MS, Pannacciulli N, Bonfiglio S, Pacak K, Krakoff J (2013) Extent and determinants of thermogenic responses to 24 h of fasting, energy balance, and five different overfeeding diets in humans. J Clin Endocrinol Metab 98(7):2791–2799. doi:10.1210/jc.2013-1289 PubMedPubMedCentralCrossRefGoogle Scholar
- 32.Caudwell P, Finlayson G, Gibbons C, Hopkins M, King N, Naslund E, Blundell JE (2013) Resting metabolic rate is associated with hunger, self-determined meal size, and daily energy intake and may represent a marker for appetite. Am J Clin Nutr 97(1):7–14. doi:10.3945/ajcn.111.029975 PubMedCrossRefGoogle Scholar
- 34.Blundell JE, Caudwell P, Gibbons C, Hopkins M, Naslund E, King NA, Finlayson G (2012) Body composition and appetite: fat-free mass (but not fat mass or BMI) is positively associated with self-determined meal size and daily energy intake in humans. Br J Nutr 107(3):445–449. doi:10.1017/S0007114511003138 PubMedCrossRefGoogle Scholar
- 39.Weise CM, Thiyyagura P, Reiman EM, Chen K, Krakoff J (2013) Fat-free body mass but not fat mass is associated with reduced gray matter volume of cortical brain regions implicated in autonomic and homeostatic regulation. NeuroImage 64:712–721. doi:10.1016/j.neuroimage.2012.09.005 PubMedCrossRefGoogle Scholar