Energy expenditure in the etiology of human obesity: spendthrift and thrifty metabolic phenotypes and energy-sensing mechanisms

Abstract

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.

Keywords: Adaptive thermogenesis; Body weight regulation; Energy expenditure; Energy sensing; Metabolic phenotypes.

Figure 1. Disruption of energy balance due to reciprocal effects of food intake and EE

Figure 2. Relationships between the 24-h EE responses to fasting and overfeeding with a standard (Panel A) and with a low-protein (Panel B) diets

The percentage change in 24-h EE during each dietary intervention was calculated as the difference between the 24-h EE during the dietary intervention and the 24-h EE during energy balance, divided by the 24-h EE during energy balance and expressed as a percentage [28]. Data from the #NCT00523627 study registered at ClinicalTrials.gov.

Figure 3. Inverse relationships between 24-h EE change with fasting and 6-month body weight change in free-living conditions (Panel A, [28]) and weight loss after 6 weeks of caloric restriction on a clinical inpatient unit (Panel B, [29])

The percentage change in 24-h EE during each dietary intervention was calculated as the difference between the 24-h EE during the dietary intervention and the 24-h EE during energy balance, divided by the 24-h EE during energy balance and expressed as a percentage. Weight change/loss is expressed as absolute change in body weight divided the baseline weight and expressed as a percentage.

Figure 4. Positive relationships between ad libitum food intake from a vending machine inpatient study and total 24-h EE (Panel A) and 24-h EE after adjustment for its physiological determinants (Panel B)

Ad libitum food intake was the average kcals consumed over 3 days recorded by computerized vending machine systems. Twenty-four-hour EE was measured inside a whole-room calorimeter during energy balance and weight maintenance. Adjusted 24-h EE in Panel B is calculated via linear regression analysis (i.e., residuals) after adjustment for age, gender, ethnicity (Native Americans vs. whites), FM, FFM and spontaneous physical activity. Data from the #NCT00342732 study registered at ClinicalTrials.gov.