Total energy expenditure and the level of physical activity correlate with plasma leptin concentrations in five-year-old children.

Abstract

Leptin, the product of the ob gene, is a hormone secreted by adipocytes that is known to decrease food intake and increase energy expenditure in ob/ob mice. In humans, variants in the OB gene have not been detected and very little is known about the action of leptin on food intake and energy expenditure, although circulating leptin concentrations are positively correlated to body fat stores. The purpose of this study was to assess the relationship between fasting plasma leptin concentrations and energy expenditure in 123 5-yrold Pima Indian children (67 males/76 females). Body composition was assessed by isotopic water dilution ( 18 O) whereas total energy expenditure (TEE) and resting metabolic rate (RMR) were measured using doubly labeled water and indirect calorimetry, respectively. The physical activity level was calculated as the ratio of TEE:RMR. Plasma leptin concentrations were positively correlated to percent body fat ( r ϭ 0.84, P Ͻ 0.0001), but were similar in boys and girls after adjusting for percent body fat. Most importantly, we found that, independent of the percentage of body fat, plasma leptin concentrations correlated with TEE (in absolute values, r ϭ 0.37, P Ͻ 0.0001, or adjusted for body size r ϭ 0.42; P Ͻ 0.0001) and with physical activity level ( r ϭ 0.26, P Ͻ 0.01), but not RMR. These results suggest that, as in animal models, leptin plays a role in energy expenditure in humans. IntroductionLeptin, the product of the mouse ob gene, is a hormone secreted by adipocytes (1) that decreases food intake (2-5) and increases body temperature (2), metabolic rate (2, 3), and physical activity (2), resulting in a rapid decline in body weight in the ob/ob mouse (2-5). Leptin is believed to regulate food intake through a negative feedback signal between adipose tissue stores and the satiety centers in the hypothalamus, possibly mediated by neuropeptide Y (5, 6). Regulation of energy metabolism by leptin may stem from stimulation of sympathetic nervous system activity, independent of food intake (7).In humans, variants in the OB gene have not been detected (8); instead, circulating leptin concentrations are positively correlated to body fat stores and body mass index (9, 10), suggesting defects in leptin signaling pathways in obese individuals (11). However, low plasma leptin concentrations have been reported in Pima Indians who subsequently gained weight as compared with Pima Indians who maintained their weight (12), suggesting that leptin may play a role in the development of obesity. Whether this is due to excess food intake, low levels of energy expenditure, or both is not known.In the present study, we have investigated the relationship between fasting plasma leptin concentrations and energy metabolism in 123 5-yr-old children, a group that is prone to obesity. As expected, plasma leptin concentrations were positively correlated to percent body fat. However, independent of body fat, leptin concentrations correlated with total energy expenditure (TEE, 1 absolute or adjusted for body size) ...

Leptin Levels Are Associated with Fat Oxidation and Dietary‐Induced Weight Loss in Obesity

“…However, these correlations were found to be independent of changes in body composition only in the study of Doucet et al (45). A positive association between leptin and EE has been described previously in cross-sectional studies pertaining to humans (17)(18)(19)(20)(21). In one study, however, leptin was not controlled for differences in FM (18).…”

“…In one study, however, leptin was not controlled for differences in FM (18). However, in a group of lean and obese 5-year-old Pima Indian children, Salbe et al (17) found that fasting leptin concentration was correlated positively and independently with both total EE assessed by doubly labeled water and with physical activity level. In another study, a nearly significant positive relationship was seen between leptin and EE under free-living conditions in women, after adjusting for differences in body fat percentage (19).…”

“…Findings from some previous studies in humans have supported the hypothesis of a role of leptin in stimulating EE (7,(17)(18)(19)(20)(21), whereas others have failed to find such relationship (22)(23)(24)(25). Furthermore, inverse correlations between fasting plasma leptin and resting metabolic rate have been reported in obese subjects, in contrast to lean individuals, supporting the hypothesis of leptin-resistance in obesity (26 -28).…”

Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y

“…Therefore NPY is one factor which modulates the food intake response to estrogen, however, our data does not rule out the possibility that other hormones (such as insulin and glucocorticoids) and neuropeptides (such as a-MSH, CART and MCH) also play a role. Our finding that central leptin administration is capable of increasing physical activity in sham-operated rats is of interest because there is some discrepancy in the literature as to whether leptin is capable of altering physical activity in human subjects 46,47 and an effect in animals has previously only been shown in the highly leptin sensitive ob=ob mouse. 48 Physical inactivity rather than hyperphagia or reduced resting energy expenditure appeared to maintain body weight at an elevated level in estrogen-deficient rats.…”

Differential and genetically separable associations of leptin with obesity-related traits

“…21 However, most studies in human subjects have found no relationship between leptin and physical activity levels, 22,23 with only one study in children showing a positive relationship. 24 The apparent inability of leptin to in¯uence physical activity in adult human subjects is also illustrated in a recent study that has shown that the activation of spontaneous physical activity in subjects who are resistant to weight gain after overfeeding is not mediated by leptin. 25 There is also some discrepancy in the literature as to whether circulating leptin concentrations in¯uence other components of energy expenditure such as resting energy expenditure.…”