Increased resting energy expenditure, fat oxidation, and food intake in patients with highly active antiretroviral therapy-associated lipodystrophy

Highly active antiretroviral therapy (HAART) is associated with metabolic adverse events such as lipodystrophy in human immunodeficiency virus (HIV)-infected patients. The objective of the present study was to evaluate the effects of HAART-associated lipodystrophy on resting energy expenditure and caloric intake. In this cross-sectional study we compared resting energy expenditure (REE) and energy intake in 30 HAART-treated patients with lipodystrophy (HAART+LD+) with 13 HAART-treated patients without lipodystrophy (HAART+LD-). REE was measured using indirect calorimetry, and energy intake was recorded as a 3-day diary of food intake. REE (5,180+/-160 vs. 4,260+/-150 J/min, P<0.01) and also REE expressed per fat-free mass (86+/-1 vs. 78+/-2 J.kg fat-free mass-1.min-1, P<0.01) were significantly higher in the HAART+LD+ than the HAART+LD- group. Rate of lipid oxidation was significantly higher in the HAART+LD+ than the HAART+LD- group. Total energy and fat intakes were significantly increased in the HAART+LD+ compared with the HAART+LD- group. These results imply that HAART-associated lipodystrophy is associated with increased REE and lipid oxidation and with increased caloric and fat intake.     

Proinflammatory cytokines and the hypermetabolism of children with sickle cell disease

Sickle cell anemia (HbSS) includes chronic inflammation, but the origin is unclear. We hypothesized that in stable HbSS patients the inflammation was associated with hypermetabolism. We compared selected hypermetabolic and key immunomodulator indicators in HbSS versus control children and examined associations between measures of hypermetabolism and inflammation. Twelve fasting asymptomatic HbSS children 6-12 years and 9 controls matched for age, gender and fat mass (FM) were studied. Proportional reticulocyte count (retic%) and resting energy expenditure (REE) represented hypermetabolism, and C-reactive protein (CRP) indicated inflammation. Proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), chemokine monocyte chemoattractant protein-1 (MCP-1), and energy balance cytokine leptin were measured. Methods were indirect calorimetry, enzyme-linked immunosorbent assay, and radioimmunoassay. Statistical analysis included simple correlation and regression analysis. REE (51 +/- 6 vs. 43 +/- 12 kcal/kg per fat-free mass (FFM), mean +/- SD), retic% (12 +/- 4 vs. 0.7 +/- 0.3%), CRP (5 +/- 3 vs. 0.3 +/- 0.4 mg/liter), and IL-6 (71 +/- 40 vs. 20 +/- 7 pg/ml) were significantly higher for HbSS than controls (P < 0.05). Conversely, leptin (0.1 +/- 0.1 vs. 2 +/- 1 microg/liter per kgFM) and MCP-1 (34 +/- 5 vs. 41 +/- 4 pg/ml) were significantly lower for the HbSS subjects (P < 0.01). TNF-alpha was not significantly different. There were no significant associations between REE or retic% and any cytokine measured. However, CRP was significantly associated with REE in HbSS (r = 0.8, P = 0.003) and an important predictor of REE/FFM. We provide new evidence for low circulating levels of inflammatory chemokine MCP-1 in stable HbSS children, confirm mostly low cytokine levels, inflammation, and hypermetabolism and demonstrate association of hypermetabolism with inflammation via CRP but not via cytokines.     

Effect of Chronic Athletic Activity on Brown Fat in Young Women

BackgroundThe effect of chronic exercise activity on brown adipose tissue (BAT) is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE) secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT.PurposeWe assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status.MethodsThe protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes) between 18–25 years of age. Athletes were either oligo-amenorrheic (n = 8) or eumenorrheic (n = 8).We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition.ResultsAthletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002), higher percent lean mass (p = 0.01) and trended higher in REE (p = 0.09). BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively). We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02).BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02), and positively with percent body fat, irisin and thyroid hormones.ConclusionsOur study shows a trend for lower BAT in young female athletes compared with non-athletes, and shows associations of brown fat with menstrual status and body composition. Brown fat may undergo adaptive reductions with increasing energy deficit.     

Mediation of burn-induced hypermetabolism by CRF receptor-2 activity

Hypermetabolism and anorexia are significant problems associated with major burn trauma. Recent studies have implicated hypothalamic peptides and receptors of the corticotropin releasing factor (CRF) family as putative mediators of burn-induced hypermetabolism. Increased neuronal activity at the CRF type 2 receptor (CRF R-2) appeared particularly involved in the expression of elevated resting energy expenditure (REE) following major burn trauma. In the present study we continued these investigations of CRF R-2 mediation of burn-induced hypermetabolism, demonstrating that 3rd ventricle injection of CRF R-2 antisense oligodeoxynucleotide (ODN) normalized REE in burned rats. Similar treatments with CRF or CRF R-1 antisense ODNs had no significant effect in burned rats. In addition, 3rd ventricle injection of the selective CRF R-2 antagonist, antisauvagine-30, also reduced REE significantly in burned rats, while similar treatment with the selective CRF R-1 antagonist, antalarmin, was without effect. To determine which endogenous peptide was altered following burn we measured hypothalamic levels of urocortin (UCN) and CRF 15 days after burn injury, finding UCN was significantly elevated by nearly 3-fold, while CRF level tended to be decreased. We also assessed hypothalamic mRNA peptide and receptor expression by real-time PCR 7, 14, and 21 days post-burn, observing decreased CRF expression 7 and 21 days post-burn, decreased UCN-2 expression 7 days post-burn, and no significant alteration in UCN-1 at any time point. However, CRF R-2 mRNA was elevated at each post-burn time point. These results continue to suggest that increased neuronal activity is integrally involved in the mediation of burn-induced hypermetabolism, and that one of the UCN peptides may be the endogenous ligand affecting this receptor.     

Impaired fat-induced thermogenesis in obese subjects: the NUGENOB study

Objectives: To study energy expenditure before and 3 hours after a high‐fat load in a large cohort of obese subjects (n = 701) and a lean reference group (n = 113). Research Methods and Procedures: Subjects from seven European countries underwent a 1‐day clinical study with a liquid test meal challenge containing 95% fat (energy content was 50% of estimated resting energy expenditure). Fasting and 3‐hour postprandial energy expenditures, as well as metabolites and hormones, were determined. Results: Obese subjects had a reduced postprandial energy expenditure after the high‐fat load, independent of body composition, age, sex, research center, and resting energy expenditure, whereas within the obese group, thermogenesis increased again with increasing BMI category. Additionally, insulin resistance, habitual physical activity, postprandial plasma triacylglycerols, and insulin were all independently positively related to the postprandial energy expenditure. Resting energy expenditure, adjusted for fat‐free mass, increased with degree of obesity, a difference that disappeared after adjustment for fat mass. Furthermore, insulin resistance, fasting plasma free fatty acids, and cortisol were positively associated, whereas fasting plasma leptin and insulin‐like growth factor‐1 were negatively associated, with resting energy expenditure. Discussion: The 3‐hour fat‐induced thermogenic response is reduced in obesity. It remains to be determined whether this blunted thermogenic response is a contributory factor or an adaptive response to the obese state.     

Possible role of CRF peptides in burn-induced hypermetabolism

Hypermetabolism and anorexia are significant problems associated with major burn trauma. Recent studies have shown that hypothalamic corticotropin releasing factor (CRF) elevates metabolic rate, while neuropeptide Y (NPY) reduces it. CRF also elicits anorexia, while NPY stimulates feeding. We hypothesized that elevation of CRF and decrease of NPY may be mediators of these negative effects of burn trauma. Therefore, we assessed concentrations of CRF and NPY in hypothalamus of burned rats one, three, and twenty-one days after a 30% body surface area, full-thickness, open flame burn. In addition we determined whether a biochemical lesion of CRF receptors using 3rd ventricle injections of a saporin-CRF conjugated peptide would decrease resting energy expenditure (REE). We found a three-day period of anorexia, with REE significantly increasing three days after the burn trauma. Concentrations of NPY were increased in the PVN-containing dorsomedial region of the hypothalamus 1 and 3 days after burn trauma, but were increased further in the day 1 pair-fed rats suggesting this change was a consequence of the anorexia. Levels of CRF were decreased in the ventromedial region of the hypothalamus in day 1 and day 3 burned and PF rats. Treatment with the saporin-CRF conjugate normalized REE and reduced CRF receptor-2 density in the hypothalamus of burned rats, and blocked CRF-induced hypermetabolism in sham-burned rats. Although these results suggest a role of CRF receptors in mediating burn-induced hypermetabolism, CRF itself may not be the principle ligand, as suggested by the significant elevation of hypothalamic urocortin 15 days after burn injury.     

Body size and human energy requirements: reduced mass-specific resting energy expenditure in tall adults.

Two observations favor the presence of a lower mass-specific resting energy expenditure (REE/weight) in taller adult humans: an earlier report of height (H)-related differences in relative body composition; and a combined model based on Quetelet and Kleiber's classic equations suggesting that REE/weight proportional, variantH(-0.5). This study tested the hypothesis stating that mass-specific REE scales negatively to height with a secondary aim exploration of related associations between height, weight (W), surface area (SA), and REE. Two independent data sets (n = 344 and 884) were evaluated, both with REE measured by indirect calorimetry and the smaller of the two including fat estimates by dual-energy X-ray absorptiometry. Results support Quetelet's equation (W proportional, variantH(2)), but Kleiber's equation approached the interspecific mammal form (REE proportional, variantW(0.75)) only after adding adiposity measures to weight and age as REE predictors. REE/weight scaled as H( approximately (-0.5)) in support of the hypothesis with P values ranging from 0.17 to <0.001. REE and SA both scaled as H( approximately 1.5), and REE/SA was nonsignificantly correlated with height in all groups. These observations suggest that adiposity needs to be considered when evaluating the intraspecific scaling of REE to weight; that relative to their weight, taller subjects require a lower energy intake for replacing resting heat losses than shorter subjects; that fasting endurance, approximated as fat mass/REE, increases as H(0.5); and that thermal balance is maintained independent of stature by evident stable associations between resting heat production and capacity of external heat release. These observations have implications for the modeling of adult human energy requirements and associate with anthropological concepts founded on body size.     

Enhanced energy expenditure and fat oxidation in humans with high BMI scores by the ingestion of novel and non-pungent capsaicin analogues (capsinoids)

The biochemical and physiological indices were monitored in 44 subjects after 4-week capsinoids (capsaicin analogues with low pungency) intake. The subjects were randomly assigned to 3 groups: CSNs3 (3 mg/kg of capsinoids), CSNs10 (10 mg/kg of capsinoids) and the control (placebo). Measurements were performed in the morning on overnight-fasted subjects. The oxygen consumption (VO(2)), resting energy expenditure (REE) and fat oxidation increased slightly compared to pre-administration values without any adverse effects, although the increase was not significant. The increase in fat oxidation was positively and significantly correlated with the body mass index (BMI). A meta-analysis was therefore conducted on a subgroup consisting of subjects with BMI >or= 25 (n=28). As a result, not only VO(2) increased significantly (p<0.05) in the CSNs10 group, but also REE in the CSNs10 group and fat oxidation in the CSNs3 and CSNs10 groups tended to increase (p<0.1). Consequently, a capsinoids intake would be able to enhance the energy expenditure and fat burning in humans, particularly those with high BMI.     

Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues

Aging is associated with increased adiposity in white adipose tissues and impaired thermogenesis in brown adipose tissues; both contribute to increased incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating orexigenic hormone that promotes adiposity. In this study, we show that ablation of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) improves insulin sensitivity during aging. Compared to wild-type (WT) mice, old Ghsr(-/-) mice have reduced fat and preserve a healthier lipid profile. Old Ghsr(-/-) mice also exhibit elevated energy expenditure and resting metabolic rate, yet have similar food intake and locomotor activity. While GHS-R expression in white and brown adipose tissues was below the detectable level in the young mice, GHS-R expression was readily detectable in visceral white fat and interscapular brown fat of the old mice. Gene expression profiles reveal that Ghsr ablation reduced glucose/lipid uptake and lipogenesis in white adipose tissues but increased thermogenic capacity in brown adipose tissues. Ghsr ablation prevents age-associated decline in thermogenic gene expression of uncoupling protein 1 (UCP1). Cell culture studies in brown adipocytes further demonstrate that ghrelin suppresses the expression of adipogenic and thermogenic genes, while GHS-R antagonist abolishes ghrelin's effects and increases UCP1 expression. Hence, GHS-R plays an important role in thermogenic impairment during aging. Ghsr ablation improves aging-associated obesity and insulin resistance by reducing adiposity and increasing thermogenesis. Growth hormone secretagogue receptor antagonists may be a new means of combating obesity by shifting the energy balance from obesogenesis to thermogenesis.     

Adaptive thermogenesis with weight loss in humans

Adaptive thermogenesis (AT) with weight loss refers to underfeeding‐associated fall in resting and non‐resting energy expenditure (REE, non‐REE); this is independent of body weight and body composition. In humans, the existence of AT was inconsistently shown and its clinical significance has been questioned.

Objectives:

Discrepant findings are mainly due to different definitions of AT, the use of various and nonstandardized study protocols, and the limits of accuracy of methods to assess energy expenditure. With controlled underfeeding, AT takes more than 2 wk to develop. AT accounts to an average of 0.5 MJ (or 120 kcal) with a considerable between subject variance.

Design and Methods:

Low‐sympathetic nervous system activity, 3,5,3′‐tri‐iodothyronine (T3) and leptin are likely to add to AT; however, the kinetic changes of their plasma levels with underfeeding differ from the time course of AT and controlled intervention studies substituting and titrating these hormones are rare in humans. AT in response to underfeeding is independent of thermogenesis in response to either diet or cold. Although fat‐free mass (FFM) and, thus, liver, and skeletal muscle are considered as major sites of AT, cold‐induced nonshivering thermogenesis relates to the metabolism of brown adipose tissue (BAT). In humans, diet‐induced thermogenesis is related to postprandial substrate metabolism of FFM with a questionable role of BAT. Obviously, the REE component of AT differs from and its non‐REE component with respect to organ contribution as well as mechanisms. Thus, AT cannot be considered as unique.

Conclusions:

AT should be characterized based on individual components of daily energy expenditure, detailed body composition analyses, and mathematical modeling. The biological basis of AT as well as the influences of age, sex, obesity, stress, and inflammation remain to be established in humans.     

Relationships of resting energy expenditure with body fat distribution and abdominal fatness in Japanese population

Body fat distribution and abdominal fatness are indicators of risks for coronary heart disease. However, the relationships between resting energy expenditure (REE) and the body fat distribution or the abdominal fatness are unclear. We examined the relationships of REE with whole-body fat distribution (waist, hip and waist-to-hip ratio: WHR) and abdominal fatness (intra-abdominal fat: IF and subcutaneous fat: SF) after adjustment for body composition. 451 men and 471 women were subdivided into two groups, 40-59 years: middle-aged group and 60-79 years: elderly group. REE was measured by an indirect calorimetry system. Percentage of fat mass (%FM), fat mass (FM) and fat-free mass (FFM) were assessed by a dual-energy x-ray absorptiometry method. The IF area (IFA) and SF area (SFA) at the level of the umbilicus were measured using computed tomography. Circumference of waist and hip were measured in a standing position. The WHR, waist circumference and SFA did not significantly (p>0.05) associate with the REE after adjusting for FM, FFM and age in any of the groups. The adjusted REE was significantly and inversely correlated with hip (r=-0.159, p<0.05) and IFA (r=-0.131, p<0.05) in the elderly men. These results suggest that lower REE may contribute to greater hip and IFA rather than WHR and waist in elderly men.     

Comparison of high-protein diets and leucine supplementation in the prevention of metabolic syndrome and related disorders in mice

High-protein diets have been shown to promote weight loss, to improve glucose homeostasis and to increase energy expenditure and fat oxidation. We aimed to study whether leucine supplementation is able to mimic the alleviating effects of high-protein diets on metabolic syndrome parameters in mice fed high-fat diet.Male C57BL/6 mice were fed for 20 weeks with semisynthetic high-fat diets (20% w/w of fat) containing either an adequate (10% protein, AP) or high (50% protein, HP) amount of whey protein, or an AP diet supplemented with l-leucine corresponding to the leucine content of the HP diet (6% leucine, AP+L). Body weight and composition, energy expenditure, glucose tolerance, hepatic triacylglycerols (TG), plasma parameters as well as expression levels of mRNA and proteins in different tissues were measured. HP feeding resulted in decreased body weight, body fat and hepatic TG accumulation, as well as increased insulin sensitivity compared to AP. This was linked to an increased total and resting energy expenditure (REE), decreased feed energy efficiency, increased skeletal muscle (SM) protein synthesis, reduced hepatic lipogenesis and increased white fat lipolysis. Leucine supplementation had effects that were intermediate between HP and AP with regard to body composition, liver TG content, insulin sensitivity, REE and feed energy efficiency, and similar effects as HP on SM protein synthesis. However, neither HP nor AP+L showed an activation of the mammalian target of rapamycin pathway in SM. Leucine supplementation had no effect on liver lipogenesis and white fat lipolysis compared to AP. It is concluded that the essential amino acid leucine is able to mimic part but not all beneficial metabolic effects of HP diets.     

Genes and biochemical pathways in human skeletal muscle affecting resting energy expenditure and fuel partitioning

Genes influencing resting energy expenditure (REE) and respiratory quotient (RQ) represent candidate genes for obesity and the metabolic syndrome because of the involvement of these traits in energy balance and substrate oxidation. We aim to explore the molecular basis for individual variation in REE and fuel partitioning as reflected by RQ. We performed microarray studies in human vastus lateralis muscle biopsies from 40 healthy subjects with measured REE and RQ values. We identified 2,392 and 1,115 genes significantly correlated with REE and RQ, respectively. Genes correlated with REE and RQ encompass a broad array of functions, including carbohydrate and lipid metabolism, gene expression, mitochondrial processes, and membrane transport. Microarray pathway analysis revealed that REE was positively correlated with upregulation of G protein-coupled receptor signaling (meet criteria/total genes: 65 of 283) involved in autonomic nervous system functions, including those receptors mediating adrenergic, dopamine, γ-aminobutyric acid (GABA), neuropeptide Y (NPY), and serotonin action (meet criteria/total genes: 46 of 176). Reduced REE was associated with an increase in genes participating in ubiquitin-proteasome-dependent proteolytic pathways (58 of 232). Serine-type peptidase activity (9 of 76) was positively correlated with RQ, while genes involved in the protein phosphatase type 2A complex (4 of 9), mitochondrial function and cellular respiration (38 of 315), and unfolded protein binding (19 of 97) were associated with reduced RQ values and a preference for lipid fuel metabolism. Individual variations in whole body REE and RQ are regulated by differential expressions of specific genes and pathways intrinsic to skeletal muscle.     

Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution.

The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance. Increased intramyocellular lipid (IMCL) concentrations are thought to contribute to insulin resistance, being linked to metabolic and body composition variables. We examined 46 women: HIV infected with fat redistribution (n = 25), and age- and body mass index-matched HIV-negative controls (n = 21). IMCL was measured by 1H-magnetic resonance spectroscopy, and body composition was assessed with computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging. Plasma lipid profile and markers of glucose homeostasis were obtained. IMCL was significantly increased in tibialis anterior [135.0 +/- 11.5 vs. 85.1 +/- 13.2 institutional units (IU); P = 0.007] and soleus [643.7 +/- 61.0 vs. 443.6 +/- 47.2 IU, P = 0.017] of HIV-infected subjects compared with controls. Among HIV-infected subjects, calf subcutaneous fat area (17.8 +/- 2.3 vs. 35.0 +/- 2.5 cm2, P < 0.0001) and extremity fat by DEXA (11.8 +/- 1.1 vs. 15.6 +/- 1.2 kg, P = 0.024) were reduced, whereas visceral abdominal fat (125.2 +/- 11.3 vs. 74.4 +/- 12.3 cm2, P = 0.004), triglycerides (131.1 +/- 11.0 vs. 66.3 +/- 12.3 mg/dl, P = 0.0003), and fasting insulin (10.8 +/- 0.9 vs. 7.0 +/- 0.9 microIU/ml, P = 0.004) were increased compared with control subjects. Triglycerides (r = 0.39, P = 0.05) and extremity fat as percentage of whole body fat by DEXA (r = -0.51, P = 0.01) correlated significantly with IMCL in the HIV but not the control group. Extremity fat (beta = -633.53, P = 0.03) remained significantly associated with IMCL among HIV-infected patients, controlling for visceral abdominal fat, abdominal subcutaneous fat, and antiretroviral medications in a regression model. These data demonstrate increased IMCL in HIV-infected women with a mixed lipodystrophy pattern, being most significantly associated with reduced extremity fat. Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women.     

Resistance training increases total energy expenditure and free-living physical activity in older adults.

The purpose of this study was to determine what effects 26 wk of resistance training have on resting energy expenditure (REE), total free-living energy expenditure (TEE), activity-related energy expenditure (AEE), engagement in free-living physical activity as measured by the activity-related time equivalent (ARTE) index, and respiratory exchange ratio (RER) in 61- to 77-yr-old men (n = 8) and women (n = 7). Before and after training, body composition (four-compartment model), strength, REE, TEE (doubly labeled water), AEE (TEE - REE + thermic response to meals), and ARTE (AEE adjusted for energy cost of standard activities) were evaluated. Strength (36%) and fat-free mass (2 kg) significantly increased, but body weight did not change. REE increased 6.8%, whereas resting RER decreased from 0.86 to 0.83. TEE (12%) and ARTE (38%) increased significantly, and AEE (30%) approached significance (P = 0.06). The TEE increase remained significant even after adjustment for the energy expenditure of the resistance training. In response to resistance training, TEE increased and RER decreased. The increase in TEE occurred as a result of increases in both REE and physical activity. These results suggest that resistance training may have value in increasing energy expenditure and lipid oxidation rates in older adults, thereby improving their metabolic profiles.     

Cardiac Parasympathetic Activity Is Increased by Weight Loss in Healthy Obese Women

Objective: We studied the effect of weight reduction on cardiac parasympathetic activity (PSA) in obese women. We also studied the relationship between the changes of PSA, resting energy expenditure (REE), and major cardiovascular risk factors. Research Methods and Procedures: Changes of cardiac vagal tone, an index of PSA, REE, and major cardiovascular risk factors, were measured in 52 healthy obese women after a 6‐month weight reduction. Ten of the women were remeasured at 12 and 24 months. Cardiac vagal tone was assessed by a vagal tone monitor and REE by indirect calorimeter. Results: Cardiac vagal tone increased significantly (p = 0.046), averaging a 9.5% weight loss in 6 months. The vagal tone increased further with weight loss during the following 6 months, and thereafter, it declined with weight regain. The increase of cardiac vagal tone correlated significantly with decreases of body weight, fat mass, waist circumference, serum insulin, and heart rate. REE adjusted for fat‐free mass and age did not change with weight loss and was not related to cardiac vagal tone at any time‐point. Discussion: Cardiac PSA activity increases with weight loss in obese women. This increase may not be maintained long‐term if body weight is regained. The rise of cardiac PSA is correlated with decreases of body fat mass, abdominal fat, serum insulin, and heart rate. Cardiac PSA is not related to REE.     

In vivo rabbit hindquarter model for assessment of regional burn hypermetabolism.

Severe burn injury evokes hypermetabolism and muscle wasting, despite nominally adequate nutrition. Although there is much information on whole organism and isolated tissue metabolism after burn injury, data examining regional burn hypermetabolism in vivo are lacking. Using surgically implanted (general anesthesia) regional vascular catheters and primed constant infusion of l-[1-(13)C]phenylalanine tracer, we have determined in vivo burn-induced alterations in rabbit hindquarter protein and energy metabolism. Burn injury evokes increased whole body resting energy expenditure and phenylalanine turnover, accompanied by significantly increased hindquarter proteolysis, creating a negative protein balance in burned rabbit hindquarter. Hindquarter oxygen consumption showed an increase after burn injury, but it did not reach statistical significance. Burn-induced changes in hindquarter protein turnover account for approximately one-third of the whole animal hypermetabolism. This model offers a system for regional manipulation of postburn hypermetabolism.     

Mild Calorie Restriction Induces Fat Accumulation in Female C57BL/6J Mice

This study investigated the effects of mild calorie restriction (CR) (5%) on body weight, body composition, energy expenditure, feeding behavior, and locomotor activity in female C57BL/6J mice. Mice were subjected to a 5% reduction of food intake relative to baseline intake of ad libitum (AL) mice for 3 or 4 weeks. In experiment 1, body weight was monitored weekly and body composition (fat and lean mass) was determined at weeks 0, 2, and 4 by dual energy X‐ray absorptiometry. In experiment 2, body weight was measured every 3 days and body composition was determined by quantitative magnetic resonance weekly, and energy expenditure, feeding behavior, and locomotor activity were determined over 3 weeks in a metabolic chamber. At the end of both experiments, CR mice had greater fat mass (P < 0.01) and less lean mass (P < 0.01) compared with AL mice. Total energy expenditure (P < 0.05) and resting energy expenditure (P < 0.05) were significantly decreased in CR mice compared with AL mice over 3 weeks. CR mice ate significantly more food than AL mice immediately following daily food provisioning at 1600 hours (P < 0.01). These findings showed that mild CR caused increased fat mass, decreased lean mass and energy expenditure, and altered feeding behavior in female C57BL/6J mice. Locomotor activity or brown adipose tissue (BAT) thermogenic capacity did not appear to contribute to the decrease in energy expenditure. The increase in fat mass and decrease in lean mass may be a stress response to the uncertainty of food availability.     

Increased adiposity in DNA binding-dependent androgen receptor knockout male mice associated with decreased voluntary activity and not insulin resistance

In men, as testosterone levels decrease, fat mass increases and muscle mass decreases. Increased fat mass in men, in particular central obesity, is a major risk factor for type 2 diabetes, cardiovascular disease, and all-cause mortality. Testosterone treatment has been shown to decrease fat mass and increase fat-free mass. We hypothesize that androgens act directly via the DNA binding-dependent actions of the androgen receptor (AR) to regulate genes controlling fat mass and metabolism. The aim of this study was to determine the effect of a global DNA binding-dependent (DBD) AR knockout (DBD-ARKO) on the metabolic phenotype in male mice by measuring body mass, fat mass, food intake, voluntary physical activity, resting energy expenditure, substrate oxidation rates, serum glucose, insulin, lipid, and hormone levels, and metabolic gene expression levels and second messenger protein levels. DBD-ARKO males have increased adiposity despite a decreased total body mass compared with wild-type (WT) males. DBD-ARKO males showed reduced voluntary activity, decreased food intake, increased serum leptin and adiponectin levels, an altered lipid metabolism gene profile, and increased phosphorylated CREB levels compared with WT males. This study demonstrates that androgens acting via the DNA binding-dependent actions of the AR regulate fat mass and metabolism in males and that the increased adiposity in DBD-ARKO male mice is associated with decreased voluntary activity, hyperleptinemia and hyperadiponectinemia and not with insulin resistance, increased food intake, or decreased resting energy expenditure.     

Acute Administration of Phenylpropanolamine Fails to Affect Resting Energy Expenditure in Men of Normal Weight

RUSHING, PA, SE WINDERS, SL WATSON, RC KLESGES. Acute administration of phenylpropanolamine fails to affect resting energy expenditure in men of normal weight. Studies have consistently found that dieters using over-the-counter weight control products containing phenylpropanolamine (PPA) are more successful at losing weight than those who do not. To explore the possibility that drug-induced metabolic changes contribute to weight loss associated with this compound, this study investigated the effects of PPA on resting metabolic rate in 20 healthy men of normal weight between the ages of 18 and 29. After the arrival of the subjects to the laboratory, blood pressure was taken and resting energy expenditure (REE) and respiratory quotient (RQ) were assessed for 20 minutes (Baseline) via indirect calorimetry. Half of the subjects were then given 75 mg of immediate-release PPA (administered orally via a gelatin capsule), while the other half received placebo. Immediately after drug administration, metabolic rate was measured for an additional 95 minutes (During Drug). After this assessment, blood pressure was again measured. Although significant increases in both systolic and diastolic blood pressure were observed after PPA administration, the drug had no effect on REE or RQ. These results, consistent with that previously reported in mildly overweight women, further establish that it is unlikely that drug-induced metabolic changes contribute to PPA-induced weight loss in humans.