Serum leptin levels and resting energy expenditure during weight gain in a patient with anorexia nervosa: a case study

Patients with anorexia nervosa (AN) are suited to study the effects of both an exceedingly low and high leptin secretion on energy expenditure and metabolism, because their serum leptin levels are below the reference range of healthy controls during the acute stage and above the reference range upon short‐term weight restoration. In this study we determined body weight, temperature, pulse, blood pressure, body composition, blood cell counts, serum levels of thyroid hormones (fT₃ and fT₄), thyroid stimulating hormone (TSH), and leptin and resting energy expenditure (REE) during inpatient treatment of a 14‐year old female with AN. Most variables increased over the 33‐week observation period. REE as measured with indirect calorimetry increased by 55 per cent from 780 to 1210 kcal/day. REE corrected for lean body mass (LBM) increased by 17 per cent. We conclude that the increased leptin secretion during weight gain possibly contributes to some of the observed phenomena. Copyright © 1999 John Wiley & Sons, Ltd and Eating Disorders Association.     

Food intake regulation by leptin: Mechanisms mediating gluconeogenesis and energy expenditure

Regulation of blood glucose levels and body fat is critical for survival.Leptin circulates freely in blood and controls body weight and food intake mainly through hypothalamic receptors and regulates glucose metabolism in the liver both directly through leptin receptors and indirectly via the hypothalamic receptors of central nervous system.Leptin affects food intake regulation and eventually glucose metabolism, lipometabolism,endocrine and immune functions, reproductive function, adipose tissue metabolism and energy expenditure.Leptin also exerts peripheral effects directly on glucose metabolism and gluconeogenesis.Most of obese human subjects have elevated plasma levels of leptin associated to the size of their total adipose tissue mass.Hence gluconeogenic function may be an essential factor in the regulation of nutritional intake and weight gain.The aim of this review is therefore to identify and module the possible effects of leptin with special application in gluconeogenesis.In addition, this review includes the study of fat consumption and energy expenditure in the body.Specific modulation of leptin receptors and adipose tissues functioning could have important inference on therapeutic strategies.     

Sex hormone suppression reduces resting energy expenditure and {beta}-adrenergic support of resting energy expenditure

Resting energy expenditure (REE) decreases with aging and may decrease in women as a result of the menopause, potentially contributing to weight gain. REE has been observed to fluctuate during the menstrual cycle, suggesting regulation by sex hormones. The aim of the present study was to determine the effects of suppressing estrogen and progesterone on REE. Fourteen premenopausal women, 29 +/- 5 yr old (mean +/- sd), were studied in the midluteal menstrual phase (ML) and after 6 d of GnRH antagonist therapy (GnRHant) administered in the follicular menstrual phase. REE was measured by indirect calorimetry in the morning after a 12-h fast and again during beta-adrenergic blockade to determine sympathetic nervous system (SNS) support of REE. Treatment with GnRHant significantly decreased REE (1405 +/- 42 vs. 1334 +/- 36 kcal/d, mean +/- se, ML vs. GnRHant; P = 0.002). Additionally, SNS blockade tended to alter REE more during ML than during GnRHant (-19 +/- 10 vs. 5 +/- 11 kcal/d; P = 0.14). Suppression of sex hormones to postmenopausal levels by GnRHant reduced REE in young healthy women. These findings suggest that the withdrawal of estrogen and/or progesterone attenuates REE, possibly through a SNS-mediated mechanism.     

Relation of serum leptin levels to lipid profile in healthy children

The association of leptin with body fat concentration is well established. There is also experimental evidence of a direct effect of leptin on lipid metabolism. The aim of this study was to evaluate whether leptin levels are related to the corresponding serum lipid levels independently of body fat mass. The study population consisted of 294 phenotypically healthy school children aged 6 to 12 years. Age, sex, body weight, height, Tanner stage, and triceps skinfold thickness were recorded for all participating subjects. A blood sample was drawn in the morning after a 12-hour fast, and serum total, high-density lipoprotein (HDL), and low-density lipoprotein cholesterol; triglyceride; and leptin levels were determined. Multiple regression analysis showed that triglyceride values were positively correlated with the ln(log(e))-transformed leptin levels (beta =.01, P <.001), whereas HDL levels were inversely associated with lnleptin values (beta = -.06, P =.05) after controlling for age, sex, Tanner stage, and body mass index when each of the lipid parameters was tested separately in the regression model. However, the introduction of both triglycerides and HDL values in the same model eliminated the significance of association of HDL with lnleptin, and the positive relationship of triglycerides with lnleptin remained significant. Our results indicate that triglycerides are independently associated with leptin levels after controlling for any known confounder.     

The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure

Ghrelin is a gastric hormone that exerts a stimulatory effect on appetite and fat accumulation. Ser(3) octanoylation is regarded as a prerequisite for ghrelin biological activity, although des-octanoylated forms may retain biological functions in vitro. Circulating ghrelin levels are usually low in obesity and in states of positive energy balance. Hence, the aim of our study was to analyze plasma active and serum total ghrelin levels in 20 obese (ages, 22-42 yr; body mass index, 41.3 +/- 1.1 kg/m(2)) and 20 lean subjects (ages, 22-43 yr; body mass index, 22.4 +/- 0.6 kg/m(2)) as well as their relationship to measures of glucose homeostasis, body fat, and resting energy expenditure (REE). The measured/predicted REE percentage ratio was calculated to subdivide groups into those with positive (> or = 100% ) and negative (<100%) ratio values. In obese patients, plasma active (180 +/- 18 vs. 411 +/- 57 pg/ml; P < 0.001) and serum total ghrelin levels (3650 +/- 408 vs. 5263 +/- 643 pg/ml; P < 0.05) were significantly lower when compared with lean subjects. Hence, ghrelin activity, defined as the proportion of active over total ghrelin levels, was similarly reduced in the obese state (6.1 +/- 0.9% vs. 8.4 +/- 1%; P < 0.05). There was a significant correlation between active and total ghrelin (r = 0.62; P < 0.001), and between total ghrelin and insulin (r = -0.53; P < 0.001) or insulin resistance using the homeostatis model of assessment-insulin resistance (r = -0.49; P < 0.001) approach. Significantly higher active ghrelin levels (214 +/- 22 vs. 159 +/- 30 pg/ml; P < 0.05) and ghrelin activity (8 +/- 1.7% vs. 4.9 +/- 0.9%; P < 0.05) were observed in patients with positive compared with negative measured/predicted REE ratio values. Our study shows that obesity is associated with an impairment of the entire ghrelin system. The observation that ghrelin is further decreased in cases of abnormal energy profit adds new evidence to the relationship between ghrelin activity and energy balance in obesity.     

Persistent suppression of resting energy expenditure after acute hypoxia

Resting energy expenditure (REE) is known to be influenced by various ambient conditions such as oxygen supply. Investigations in healthy subjects during acute hypoxia revealed a drop in REE, but persistent effects after hypoxia had ended have not been examined so far. Although indirect calorimetry is a well-established method to measure REE, it may lead to false conclusions when hyperventilation, rise in lactate or catecholamines, and decrease of food intake accompany hypoxia. Therefore, we determined REE in healthy men after hypoxia had ended and under conditions of controlled energy supply during a glucose clamp. In a double-blind crossover study design, we induced hypoxia for 30 minutes by decreasing oxygen saturation to 75% (vs 96% in a control session) in 13 healthy men. Indirect calorimetry was performed at baseline and 150 minutes after hypoxia had ended. Plasma glucose was held stable between 4.5 and 5.5 mmol/L, and lactate as well as catecholamine concentrations were monitored. In parallel, we measured alterations in hormones of the hypothalamic-pituitary-thyroid axis, which is one known factor mediating changes in REE. Resting energy expenditure was decreased after hypoxia (from 1656+/-80 to 1564+/-97 kcal/d) as compared with the normoxic control condition (1700+/-82 to 1749+/-79 kcal/d, P=.037), whereas the respiratory quotient remained stable (P=.79). Plasma lactate, catecholamine levels, and the pituitary thyroid secretory activity were unchanged after hypoxia (P>.2). Our data demonstrate that the REE decrease persists 150 minutes after acute hypoxia, indicating an adaptation of energy metabolism. This should be valued as an additive pathogenic factor in diseases with disturbed energy metabolism.     

慢性阻塞性肺疾病患者静息能量与呼吸力学及气体交换关系的研究

目的　探究慢性阻塞性肺疾病 (COPD)患者静息能量消耗 (REE)与肺通气功能、呼吸驱动及呼吸肌功能间的关系。方法　用canopy法间接测定 2 6例COPD患者和 2 1例健康对照者的REE、氧耗量 ( VO2 )、二氧化碳产生量 ( VCO2 )及呼吸商 (RQ)。同时测静息肺通气功能、口腔阻断压(P0 1)、最大吸气压 (PIMAX)及最大呼气压 (PEMAX) ,并进行动脉血气分析。结果　 (1)COPD组患者REE实测值 [(15 77 6 9± 311 31)kcal/d]较健康对照组 [(1388 2 9± 194 89)kcal/d]高 (P <0 0 5 ) ;PIMAX[(44 5 3± 10 6 0 )mmHg]较健康对照组 [(71 4 3± 2 2 34)mmHg]低 (P <0 0 1) ,P0 1/PIMAX(0 0 6 8± 0 0 2 6 )较健康对照组 (0 0 39± 0 0 14 )高 (P <0 0 5 ) ;第 1秒钟用力呼气容积 (FEV1)占预计值的百分比 [(5 0 4 6± 2 1 35 ) % ]、动脉血氧分压 (PaO2 ) [(77 72± 8 84 )mmHg]、动脉血氧饱和度(SaO2 ) [(92 5 4± 2 5 5 ) % ]均较健康对照组低 (P <0 0 1) ;心率 [(83 4 6± 11 36 )次 /min]较健康对照组 [(6 9 71± 5 73)次 /min]高 (P <0 0 5 )。 (2 )相关分析显示 ,COPD组REE实测值与身高、体重、体重指数、P0 1/PIMAX及心率呈正相关 (r分别为 0 5 7、0 6 5、0 6 2、0 4 1、0 5 1) ,与FEV1占预计     

Aerobic fitness and resting energy expenditure in young adult males

Ambiguous findings have been reported in previous studies regarding the relationships among aerobic fitness, resting metabolic rate (RMR), and the thermic effect of a meal (TEM). We reexamined the association among these variables in young nonobese men who exhibited a wide range of aerobic fitness levels. RMR was measured after an overnight fast and TEM was assessed for three hours after ingestion of a liquid meal. Preprandial and postprandial plasma levels of insulin, glucose, and thyroid hormones (total T3 and T4) were measured. Daily energy intake was estimated from three-day food diaries, body composition from underwater weighing, and aerobic fitness from a test of VO2 max. Data were analyzed with linear and curvilinear regression analysis, as well as with ANOVA to test for differences among subjects classified by fitness level (ie, untrained, moderately, and highly trained). A significant correlation was found between RMR and VO2 max (r = .77, P less than .01). RMR adjusted for body weight and FFW was higher in highly trained men when compared to moderately and untrained individuals. However, a curvilinear relationship was found between TEM and VO2 max (P less than .05). Subjects who exhibited moderate levels of fitness showed the highest TEM, whereas a lower TEM was noted in untrained and highly trained men. These findings were observed in the absence of differences in plasma concentrations of total T3 and T4 among fitness levels. These findings suggest that highly trained men have a high RMR adjusted for their metabolic size.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased resting energy expenditure in human immunodeficiency virus-infected men

Even in the absence of anorexia and malabsorption, weight loss is frequently observed in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). To investigate whether increased resting energy expenditure (REE) might be responsible for this weight loss, indirect calorimetry was performed in 18 human immunodeficiency virus (HIV)-infected men free of clinically active opportunistic infections for at least 2 months. Patients with AIDS (n = 11) or ARC (n = 7) had 9% higher rates of REE when compared with 11 healthy volunteers (P less than .05) with similar food intake and of the same body composition. The results obtained from patients with AIDS or ARC were identical. As no differences were found between patients and controls in plasma concentrations of catecholamines, thyroid hormones, cortisol, or tumor necrosis factor, except for lower concentrations of norepinephrine in the patients (mean +/- SD, 233 +/- 111 v 367 +/- 125 ng/L, patients v controls, P less than .01), this hypermetabolism is not explained by higher levels of these catabolic hormones. The results indicate that even in the absence of acute concomitant infections, increased REE may contribute to the weight loss in patients with AIDS or ARC.     

慢性阻塞性肺疾病患者静息能量消耗测定及意义

为探讨慢性阻塞性肺疾病患者发生营养不良后能量代谢的特点及意义,测定了２８例营养不良和２４例营养状态正常的缓解期ＣＯＰＤ患者的静息能量消耗和糖、脂肪及蛋白质氧化产生能量占ＲＥＥ的比例,并与２０例健康人进行比较。结果显示,营养不良ＣＯＰＤ患者的ＲＥＥ与预计值比值明显高于营养正常的ＣＯＰＤ患者和对照组,脂肪氧化产生能量占ＲＥＥ的比例高于后两者,蛋白质氧化产生能量所占比例低于两者。提示营养不良ＣＯＰＤ患者     

Ascites increases the resting energy expenditure in liver cirrhosis

The purpose of this study was to investigate the effect of ascites on the energy metabolism of patients with liver cirrhosis. The resting energy expenditure was determined in 10 patients with liver cirrhosis and ascites of moderate or large volume. The resting energy expenditure measurement was performed using indirect calorimetry and the resting energy expenditure predictive value was calculated with the Harris-Benedict equation, both before and after removal of ascitic fluid by paracentesis. Metabolic stress factors were absent in all cases. After an interval of 11.2 +/- 7.7 days between measurements, a weight loss of 16.6 +/- 10.3 kg was observed with paracentesis. The resting energy expenditure measured by indirect calorimetry showed a statistically significant decrease from 1682 +/- 291 to 1523 +/- 240 kcal/day (P less than 0.005) after removal of ascites. The repeatability of our indirect calorimetry method only allowed for the analysis of the results in 4 of 10 patients in whom ascites removal produced a consistent decrease in resting energy expenditure. There were no statistically significant differences between the measurements obtained by indirect calorimetry and those provided by the Harris-Benedict equation, but the latter had a moderate reliability in predicting the real resting energy expenditure of every patient. Our results suggest that, far from being an inert volume, ascites may be associated, at least in some patients, with an increased resting energy expenditure and therefore accelerate the appearance of protein energy malnutrition with corresponding complications.     

Elevated bound leptin correlates with energy expenditure in cirrhotics

BACKGROUND & AIMS: Leptin, found to be elevated in patients with liver cirrhosis, may contribute to the inadequate energy expenditure and malnutrition associated with a negative prognosis for these patients. Our aim was to characterize leptin components and their relationships to body composition, resting energy expenditure (REE), and substrate use in patients with posthepatic liver cirrhosis. METHODS: Using specific radioimmunoassays, we measured free leptin and bound leptin in 27 cirrhotics and 27 matched control subjects. In the cirrhotic group, body composition and REE were determined. RESULTS: Free leptin was not different in cirrhotics and control subjects and was related to body mass index (controls: r = 0.34, P < 0.05; cirrhotics: r = 0.55, P < 0.005) and to fat mass (cirrhotics: r = 0.76, P < 0.0001). Bound leptin was significantly higher in cirrhotic subjects than in controls (P < 0.001) and was related to REE x fat-free mass(-1) (r = 0.57, P < 0.005) or to the difference between measured and estimated REE (r = 0.55, P < 0.005). CONCLUSIONS: Free leptin reflects fat mass in controls and cirrhotics. Increased serum leptin in cirrhotics is a result of increased bound leptin serum concentrations, which are positively related to energy expenditure. Moreover, bound leptin may be a useful marker for inadequate energy expenditure in patients with liver cirrhosis.     

Prediction of resting energy expenditure in severely obese Italian women

The aims of the present study were to develop and cross-validate new equations for predicting resting energy expenditure (PREE) in severely obese Italian women, and to compare their accuracy with those of the Harris-Benedict, Bernstein, WHO/FAO/UNU, Owen, Mifflin, Nelson, Siervo, Huang and Livingston equations to predict REE, using the Bland-Altman method. One hundred and eighty two women [mean body mass index (BMI) 45.6 kg/m2; 56.7% fat mass (FM)], aged 19 to 60 yr participated in this study. REE was measured by indirect calorimetry and body composition by bioelectrical analysis. Equations were derived by stepwise multiple regression analysis, using a calibration group and tested against the validation group. Two new specific equations based on anthropometric REE=Weightx0.042+Heightx3.619-2.678 (R2=0.66, SE=0.56 MJ) or body composition parameters REE=FFMx0.067+FMx0.046+1.568 (R2=0.63, SE=0.58 MJ) were generated. Mean PREE were no different from the mean measured resting energy expenditure (MREE) (<1%, p>0.800) and REE was predicted accurately (95-105% of MREE) in 60% of subjects. The WHO/FAO/UNU, Harris-Benedict and Siervo equations showed mean differences <2% and PREE was accurate in <44% of subjects. The Huang, Mifflin and Livingston equations showed a mean PREE underestimation (>5.0%, p<0.001) and PREE was accurate in <38% of subjects. The Owen, Bernstein and Nelson equations showed a greater PREE underestimation (>14%, p<0.001) in >90% of subjects. The new prediction equations allow an accurate estimation of REE in groups of severely obese women and result in lower mean differences and lower limits of agreement between PREE and MREE than commonly used equations.     

Attenuation of resting energy expenditure following hematopoietic SCT in children

Children undergoing hematopoietic SCT (HSCT) typically receive parenteral nutrition (PN) due to gastrointestinal toxicities. Accurate determination of resting energy expenditure (REE) may facilitate optimal energy provision and help avoid unintended overfeeding or underfeeding. A multicenter, prospective cohort study of children undergoing allogeneic HSCT was performed, in which REE was measured by indirect calorimetry at baseline and twice weekly until 30 days after transplantation. Change in percent predicted REE over time from admission was analyzed using repeated measures regression analysis. In all, 26 children (14 females) with a mean (s.d.) age of 14.9 (4.2) years who underwent an HLA-matched sibling or unrelated donor transplantation were enrolled. Mean (s.d.) percent predicted REE at baseline was 92.4 (15.2). Baseline REE was highly correlated with lean body mass measured by dual energy X-ray absorptiometry (r=0.78, P<0.0001). REE decreased significantly over time, following a quadratic curve to a nadir of 79% predicted at 14 days post transplantation (P<0.001) and returned to near baseline by day 30. Children undergoing HSCT exhibit a significant reduction in REE in the early weeks after transplantation, a phenomenon that places them at risk for overfeeding. Serial measurements of REE or reductions in energy intake should be considered when PN is the primary mode of nutrition.     

Endocrine regulation of uncoupling proteins and energy expenditure

Regulatory thermogenesis occurs upon exposure to the cold or during food intake. Among a variety of mechanisms leading to heat production, uncoupling of respiration in brown adipocyte mitochondria appears to be a major contributor to resistance to the cold in rodents. This uncoupling mechanism is due to the activity of uncoupling protein-1 (UCP-1), a specific carrier present in the inner membrane of mitochondria. The recent identification of UCP-2 and UCP-3, two homologues of the brown fat UCP, suggested that respiration uncoupling could contribute to thermogenesis in most tissues. Activity and expression of the three UCP's are stimulated by several neuromediators and hormones such as noradrenaline, tri-iodothyronine and leptin.     

Prediction of resting energy expenditure in severely obese Italian males

The objectives of the present study were to develop and cross-validate new equations for predicting resting energy expenditure (PREE) in severely obese Italian males, and to compare their accuracy with those of the Harris-Benedict, WHO/ FAO/UNU, Huang, Owen, Mifflin, Livingston, Nelson, Bernstein, and Cunnimgham equations in order to predict resting energy expenditure (REE), using the Bland-Altman method. One hundred and sixty-four severely obese males [mean body mass index (BMI): 45.4 kg/m2; 50.2% fat mass), aged 20 to 65 yr participated in this study. REE was measured by indirect calorimetry and body composition by bioelectrical analysis. Equations were derived by stepwise multiple regression analysis using a calibration group and tested against the validation group. Two new specific equations, based on anthropometric [REE=Weight x 0.048 + Height x 4.655 - age x 0.020 - 3.605 (R2=0.68, SE=1.14 MJ/d)] or body composition parameters [REE=fat free mass (FFM) x 0.081 + fat mass (FM) x 0.049 - age x 0.019 - 2.194 (R2=0.65, SE=1.15 MJ/d)], were generated. Mean PREE were not different from the mean measured REE (MREE) (<1%, p<0.001), REE being predicted accurately (95-105% of MREE) in 66 and 62% of subjects, respectively. The Harris-Benedict, WHO/FAO/UNU, Huang and Owen equations showed mean differences lower than 5% and PREE was accurate in less than 30% of subjects. The Mifflin, Livingston, and Nelson equations showed a mean PREE underestimation >7% (p<0.001) and PREE was accurate in less than 25% of subjects. The Bernstein and Cunningham equations showed a greater PREE underestimation (>22%, p<0.001) in more than 85% of subjects. The new prediction equations allow an accurate estimation of REE in groups of severely obese males and result in lower mean differences and lower limits of agreement between PREE and MREE than the commonly used equations.     

Short-term energy restriction reduces resting energy expenditure in patients with HIV lipodystrophy and hypermetabolism

We have previously shown that resting energy expenditure (REE) is increased in patients with HIV lipodystrophy. This hypermetabolism could be the result of an inadequate storage capacity for lipid fuel secondary to atrophy of the subcutaneous adipose tissue depot. Therefore, energy restriction may be able to alleviate this hypermetabolism. To test this hypothesis, we measured REE in HIV-infected patients with lipodystrophy and hypermetabolism and in HIV-infected and healthy controls. Measurements were taken during the overnight fasted state after 3 days on a eu-energetic diet and again after 3 days on a diet of similar composition but reduced in energy by 50%. After 3 days of eu-energetic feeding, REE was significantly higher in HIV-infected patients with lipodystrophy compared with healthy controls (139.5 +/- 1.3 vs 117.2 +/- 1.3 kJ/kg lean body mass, P < .001) and tended to be higher compared with HIV-infected subjects without lipodystrophy (139.5 +/- 13 vs 127.3 +/- 1.4 kJ/kg lean body mass, P = .06). Furthermore, energy restriction caused a significant decline in REE in patients with HIV lipodystrophy (P < .001). This dietary manipulation did not lead to a significant reduction in REE in either HIV-infected or healthy controls. This suggests that energy intake and REE may be uniquely coupled in patients with lipodystrophy as a means to dissipate energy that cannot be stored in a normal manner. A better understanding of this coupling would have important implications for weight regulation in general.