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

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.

Specific skeletal muscle sphingolipid compounds in energy expenditure regulation and weight gain in Native Americans of Southwestern heritage.

BACKGROUND/OBJECTIVES: In animal models, a role in the regulation of energy expenditure (EE) has been ascribed to sphingolipids, active components of cell membranes participating in cellular signaling. In humans, it is unknown whether sphingolipids have a role in the modulation of EE and, consequently, influence weight gain. The present study investigated the putative association of EE and weight gain with sphingolipid levels in the human skeletal muscle, a component of fat-free mass (the strongest determinant of EE), in adipose tissue and plasma. SUBJECTS/METHODS: Twenty-four-hour EE, sleeping metabolic rate (SMR) and resting metabolic rate (RMR) were assessed in 35 healthy Native Americans of Southwestern heritage (24 male; 30.2±7.73 years). Sphingolipid (ceramide, C; sphingomyelin, SM) concentrations were measured in skeletal muscle tissue, subcutaneous adipose tissue and plasma samples. After 6.68 years (0.26-12.4 years), follow-up weights were determined in 16 participants (4 females). RESULTS: Concentrations of C24:0, SM18:1/26:1 and SM18:0/24:1 in muscle were associated with 24-h EE (r=-0.47, P=0.01), SMR (r=-0.59, P=0.0008) and RMR (r=-0.44, P=0.01), respectively. Certain muscle sphingomyelins also predicted weight gain (for example, SM18:1/23:1, r=0.74, P=0.004). For specific muscle sphingomyelins that correlated with weight gain and EE (SM18:1/23:0, SM18:1/23:1 and SMR, r=-0.51, r=-0.41, respectively, all P<0.03; SM18:1/24:2 and RMR, r=-0.36, P=0.03), associations could be reproduced with SMR in adipose tissue (all r<-0.46, all P<0.04), though not in plasma. CONCLUSIONS: This study provides preliminary, novel evidence, that specific muscle and adipose tissue sphingolipid compounds are associated with EE and weight gain in Native Americans of Southwestern heritage. Further studies are warranted to investigate whether sphingolipids of different body compartments act in concert to modulate energy balance in humans.

Body composition and energy expenditure predict ad-libitum food and macronutrient intake in humans.

BACKGROUND: Obesity is the result of chronic positive energy balance. The mechanisms underlying the regulation of energy homeostasis and food intake are not understood. Despite large increases in fat mass (FM), recent evidence indicates that fat-free mass (FFM) rather than FM is positively associated with intake in humans. METHODS: In 184 humans (73 females/111 males; age 34.5±8.8 years; percentage body fat: 31.6±8.1%), we investigated the relationship of FFM index (FFMI, kg m(-2)), FM index (FMI, kg m(-2)); and 24-h energy expenditure (EE, n=127) with ad-libitum food intake using a 3-day vending machine paradigm. Mean daily calories (CAL) and macronutrient intake (PRO, CHO, FAT) were determined and used to calculate the relative caloric contribution of each (%PRO, %CHO, %FAT) and percent of caloric intake over weight maintaining energy needs (%WMENs). RESULTS: FFMI was positively associated with CAL (P<0.0001), PRO (P=0.0001), CHO (P=0.0075) and FAT (P<0.0001). This remained significant after adjusting for FMI. Total EE predicted CAL and macronutrient intake (all P<0.0001). FMI was positively associated with CAL (P=0.019), PRO (P=0.025) and FAT (P=0.0008). In models with both FFMI and FMI, FMI was negatively associated with CAL (P=0.019) and PRO (P=0.033). Both FFMI and FMI were negatively associated with %CHO and positively associated with %FAT (all P<0.001). EE and FFMI (adjusted for FMI) were positively (EE P=0.0085; FFMI P=0.0018) and FMI negatively (P=0.0018; adjusted for FFMI) associated with %WMEN. CONCLUSION: Food and macronutrient intake are predicted by FFMI and to a lesser degree by FMI. FFM and FM may have opposing effects on energy homeostasis.