Increase In Basal Metabolic Rate Research Articles

Two estimates of the metabolic costs of antibody production in migratory shorebirds: low costs, internal reallocation, or both?

We measured the costs of mounting a humoral immune response using two novel antigens (tetanus and diphtheria) in two shorebird species (Scolopacidae): Red Knot (Calidris canutus, measured in autumn) and Ruff (Philomachus pugnax, measured in spring). Metabolic rate was measured during the preinjection phase, at the building phase of the primary immune response, and at peak secondary immune response by determining the oxygen consumption of the postabsorptive birds at rest. Confirming earlier studies, Red Knots and Ruffs responded with lower antibody titers to the diphtheria than to the tetanus antigen. Although Red Knots and Ruffs produced the same amounts of antibodies, Red Knots showed a significant 13% increase in basal metabolic rate (BMR) during the secondary antibody response, whereas Ruffs showed a 15%, but only marginally significant, reduction in BMR. The results from this study suggest that the energetic costs of an immune response may be small, but the "negative cost" in Ruffs hints at the possibility of resource reallocation and the concomitant difficulty of measuring such costs during "basal" metabolic rate measurements.

Metabolic responses after severe head injury and how to optimize nutrition: A literature review

It was established by studies conducted in the 1980s and early 1990s that significant increases in basal metabolic rate and protein catabolism occur in the acute stages following severe head injury. These metabolic responses can rapidly result in malnutrition and can have significant effects on the patient's neurological recovery, immunity, and length of stay in intensive care. This paper reviews the randomized studies that have been conducted on early versus delayed feeding and on enteral versus parenteral nutrition to determine how best to manage the nutritional needs of severely head injured patients. There is insufficient evidence to advocate one route of feeding over the other, however, studies do indicate that, independent of the route, early adequate nutrition has more favourable outcomes particularly in relation to lower infection rates. The protein and caloric requirements of these patients should be based on their individual requirements as determined by their basal energy expenditure, urinary nitrogen balance and plasma protein levels. It is advocated that calories are replaced based on the patient's basal energy expenditure plus 20-40% and 2 g/kg of protein. Failure to make every attempt to meet the increased nutritional requirements of these patients puts them at risk of malnutrition with potentially detrimental consequences.

Temperature-dependent effects of cadmium on mitochondrial and whole-organism bioenergetics of oysters (Crassostrea virginica)

Intertidal mollusks are exposed to multiple stressors in estuaries, including temperature and trace metals such as cadmium, which may interactively affect their physiology. We have studied the combined effects of temperature and cadmium stress on metabolism of oysters at the whole animal and mitochondrial levels. In vivo exposure to 50 microg L(-1) Cd led to a significant increase in basal metabolic rate (BMR) in 20 degrees C-acclimated but not in 28 degrees C-acclimated oysters. Cadmium exposure resulted in a fast decrease in mitochondrial capacity to synthesize ATP in 28 degrees C-acclimated but not 20 degrees C-acclimated oysters indicating that mitochondria may be functioning closer to their capacity limits in the former group. This agrees with elevated mortality in Cd-exposed oysters at 28 degrees C but not 20 degrees C. In general, elevated temperature increased sensitivity of oysters to cadmium at mitochondrial and whole-organism levels suggesting that oyster populations may become more susceptible to trace metal pollution during seasonal warming and/or global climate change.

Analyse longitudinale des variations de la composition corporelle et du métabolisme de base d'adolescents obèses pris en charge en institution ou à domicile

The prevalence of obesity in children has increased dramatically during the past decades, and requires efficient care. Objectives. – To determine changes in anthropometric parameters and basal metabolic rate (BMR) in obese adolescents during and after 2 types of weight-reduction programs. Subjects and methods. – Twenty-six adolescents (group I, Z-score of BMI = 4.72) followed a 9-month-weight reduction program including a moderate energy restriction and regular physical activities in a specialized institution. In addition, 39 adolescents (group E, Z-score of BMI = 2.83) followed at home a 9-month-weight reduction program including medical and dietetic advices. Body composition (by impedancemetry) and BMR (by indirect calorimetry) were assessed before the beginning (M0), 4 months after (M4) and at the end (M9) of the programs, then 4 months (M13) and 16 month (M25) after the end of the weight-reduction programs. Results. – Twenty-two adolescents in group I and 20 adolescents in group E completed the study. At M0, age, body weight (BW), fat-free mass (FFM) and BMR of subjects of group I were higher (1.0 year, 36 %, 30 % and 23 %, respectively, P < 0.001), than those of group E. Pubertal stage and percentage of fat mass (FM) were not significantly different between the 2 groups. At M9, adolescents of group I showed significant reductions in BW and FM (–19 and –37 %, respectively, P < 0.001), but not significant differences in FFM. In addition, BMR decreased significantly between M0 and M4, both in absolute value (–6.7%, P < 0.001) and after adjustment for FFM (–5.8%, P < 0.001), and the difference was maintained until M9. Between M9 and M13, BW and Z-score of BMI were maintained in 12 adolescents, but increased (+9.7% and 14.8%, respectively, P < 0.001) in 10 adolescents. However, BMR did not change significantly in all adolescents. Between M13 and M25, BW, FM, FFM and BMR increased significantly (+ 13%, + 34%, + 6% et + 5%, respectively, P < 0.001). During the 25 month period, adolescents of group E showed significant increases in BW, FFM and BMR (+ 8%, + 14% and + 10%, respectively, P < 0.001), and maintained their Z-score and FM. Conclusion. – The reduction in BMR during the weight-reduction program at the institution could contribute to body weight regain in the post-obese adolescents if they do not maintain the lifestyle habits taught during the weight-reduction period. In other respects, Z-score was stabilized in 51% of domiciled obese adolescents.

Metabolic and Ventilatory Acclimatization to Cold Stress in House Sparrows (Passer domesticus)

Passerines that overwinter in temperate climates undergo seasonal acclimatization that is characterized by metabolic adjustments that may include increased basal metabolic rate (BMR) and cold-induced summit metabolism (M(sum)) in winter relative to summer. Metabolic changes must be supported by equivalent changes in oxygen transport. While much is known about the morphology of the avian respiratory system, little is known about respiratory function under extreme cold stress. We examined seasonal variation in BMR, M(sum), and ventilation in seasonally acclimatized house sparrows from Wisconsin. BMR and M(sum) increased significantly in winter compared with summer. In winter, BMR increased 64%, and M(sum) increased 29% over summer values. The 64% increase in winter BMR is the highest recorded for birds. Metabolic expansibility (M(sum)/BMR) was 9.0 in summer and 6.9 in winter birds. The metabolic expansibility of 9.0 in summer is the highest yet recorded for birds. Ventilatory accommodation under helox cold stress was due to changes in breathing frequency (f), tidal volume, and oxygen extraction efficiency in both seasons. However, the only significant difference between summer and winter ventilation measures in helox cold stress was f. Mean f in helox cold stress for winter birds was 1.23 times summer values.

The Effect Of Isoenergetic Aerobic And Strength Training Upon Basal Metabolic Rate

BACKGROUND The mechanism(s) associated with exercise-induced increases in basal metabolic rate remain unclear, however exercise energy expenditure (EE), and metabolic cost of increased fat oxidation during exercise may play a role. PURPOSE To examine the effect of isoenergetic (3.8 MJ) aerobic (AT) and strength training (ST) sessions on basal metabolic rate (BMR) and to determine whether the EE and/or exercise modality influences BMR. METHODS Thirteen normolipidemic healthy males aged 20.9±0.6 yrs (mean±SE) underwent pretests (VO2peak 45.9±2.9 ml.kg−1·min−1; Weight 71.8±5.3 kg; FFM 57.5±2.7 kg; % Body Fat 16.8±2.5) before participating in one control (CON) and two post-exercise BMR trials. Indirect calorimetry was used to calculate BMR and EE during both exercise sessions. The ST trial consisted of a 13 exercises with resistance being calculated relative to body weight, while the AT session was performed at 70% VO2peak for a duration calculated to match the ST EE. Differences between CON, ST and AT trials were analyzed with analysis of variance. RESULTS The total exercising time of the ST session (109.7±3.1 min) was longer (p < 0.05) than the AT (71.2±3.0 min), however, there was no difference in EE (AT, 3.9±0.1; ST, 3.9±0.2 MJ). Fat oxidation, carbohydrate (CHO) oxidation and RER (AT, 0.99±0.03; ST, 1.05±0.06) were the same during the AT and ST sessions; with fat oxidation contributing 11.1 and 14.8% of supplied energy during the AT and ST sessions, respectively. There was no change in BMR following either exercise session, whether it was expressed absolutely (CON, 9.5±0.6; AT, 10.6±0.7; ST, 10.2±0.7 MJ day-1) or relative to body weight (CON, 135.6±7.1; AT, 150.7±7.5; ST, 143.7±7.1 kJ day−1), FFM (CON, 166.6±8.8; AT, 185.4±9.2; ST, 180.8±10.9 kJ day−1) or muscle mass (CON, 175.0±9.2; AT, 189.2±11.3; ST, 194.6±9.6 kJ.day−1). RER was the same during the CON, and both post exercise BMR trials. There was no change in fasting plasma triglyceride concentrations following either exercise session, however, both sessions significantly (p < 0.05) reduced plasma glucose concentrations (CON, 4.73±0.1; AT, 3.83±0.1; ST 3.90±0.1 mmol.l−1). CONCLUSION Despite the relatively high EE in both the ST and AT sessions, neither produced an increase in BMR post exercise. There were no differences between ST and AT trials for FAT, CHO oxidation, RER during exercise and fasting post exercise TG concentrations. Results may suggest that, if there is an increased fat oxidation during exercise it may affect post exercise induced increases in BMR.

Short photoperiod enhances thermogenic capacity in Brandt's voles

Environmental cues play important roles in the regulation of an animal's physiology and behavior. In the present study, we examined the effects of short photoperiod (SD) on body weight as well as on several physiological, hormonal, and biochemical measures indicative of thermogenic capacity to test our hypothesis that short photoperiod stimulates increases in thermogenesis without cold stress in Brandt's voles. SD voles showed increases in basal metabolic rate (BMR) and nonshivering thermogenesis (NST) during the 4-week photoperiod acclimation. At the end, these voles (SD) had lower body weights, higher levels of cytochrome C oxidase (COX) activity and mitochondrial uncoupling protein-1 (UCP1) contents in brown adipose tissues (BAT), and higher concentrations of serum tri-iodothyronine (T 3) and thyroxine (T 4) compared to LD voles. No differences were found between male and female voles in any of the above-mentioned measurements. Together, these data indicate that SD experience enhances thermogenic capacity similarly in males and females of Brandt's voles.

Changes in basal metabolic rate during pregnancy in relation to changes in body weight and composition, cardiac output, insulin-like growth factor I, and thyroid hormones and in relation to fetal growth

The total energy cost of pregnancy is largely due to an elevated basal metabolic rate (BMR). Large variations in the BMR response to pregnancy have been reported, but the factors associated with this variability are incompletely known. The objective was to identify factors associated with variability in the BMR response to pregnancy. In 22 healthy women, BMR, body weight (BW), total body fat (TBF), fat-free mass (FFM), circulatory variables, serum concentrations of insulin-like growth factor I (IGF-I), and thyroid hormones were measured before pregnancy and in gestational weeks 14 and 32. BMR and BW were also measured in gestational weeks 8, 20, and 35. Fetal weight was estimated in gestational week 31. In gestational week 14, the increase in BMR correlated significantly with the corresponding increase in BW and with the prepregnancy percentage of TBF. Together these variables explained approximately 40% of the variability in the BMR response. In gestational week 32, the increase in BMR correlated significantly with the corresponding changes in BW, TBF, FFM, IGF-I, cardiac output, and free triiodothyronine. The increase in BW in combination with fetal weight or with the elevated concentration of IGF-I in serum explained approximately 60% of the variability in the increase in BMR. Weight gain and the prepregnancy percentage of TBF-ie, factors related to the maternal nutritional situation-are important factors with regard to the variability in the BMR response to pregnancy. Thus, it is important to consider the nutritional situation before and during gestation when assessing pregnancy energy requirements.

The effects of reduced temperature and photoperiod on body composition in hibernator and non-hibernator rodents

We examined the differential change in body composition in response to a gradual reduction in both environmental temperature and photoperiod to mimic seasonal fluctuations in the wild (summer–winter transition), from ambient to 5°C and 1:23 light:dark for 8 weeks. In contrast to acute cold exposure used in previous studies, cold-acclimated rats showed an initial increase in growth rate relative to normothermic controls, possibly due to cold-stimulated hyperphagia. In hamsters, maintenance of growth rate during initial cold exposure reflects the intrinsic high oxidative capacity, while subsequent cessation of growth is consistent with the preparation for hibernation. Cold-induced atrophy of skeletal muscles coincided with increased capacity for non-shivering thermogenesis (NST) associated with a greater mass of brown adipose tissue (BAT). Cardiac hypertrophy may compensate for an increase in total peripheral resistance and/or work load of heart in both species (40% and 20%, respectively), while hypertrophy of lung (20% and 40%) and diaphragm muscle (7% and 40%) was consistent with increased ventilation associated with a cold-induced increase in basal metabolic rate. Gonadal atrophy in hamsters (160%) may be an energy saving strategy during the non-reproductive season, while maintenance of other endocrine (thyroid, adrenal, pineal) gland masses reflects the continued importance of hormonal regulation of homeostasis. The interspecific differences appear to accommodate the increased demands of shivering thermogenesis (skeletal muscle hypertrophy) or NST (BAT, diaphragm) in rats and hamsters, respectively. Those systems representing cardiovascular and metabolic control completed their adaptation quickly (within 4-week cold acclimation), while the respiratory and reproductive systems continued to respond to a further 4-week exposure. This differential time course may reflect the relative strength of selection pressure on these systems for the process of cold acclimation.

Effects of helium/oxygen and temperature on aerobic metabolism in the marsupial sugar glider, Petaurus breviceps.

Helox (79% helium and 21% oxygen) has often been used for thermobiological studies, primarily because helium is thought to be metabolically inert and to produce no adverse effects other than increasing heat loss. However, these assumptions have been questioned. As basal metabolic rate (BMR) represents maintenance energy requirements for vital body functions, potential physiological effects of helox should be reflected in changes of BMR. In this study, sugar gliders were subjected to both air and helox atmospheres over a wide range of T(a)'s, including the thermoneutral zone (TNZ), to determine (1) whether helox has any influence other than on heat loss and (2) the maximum heat production (HP(max)) and thermal limits of this species. Although thermal conductance in the TNZ increased in helox, BMR was similar in air and helox (0.55+/-0.07 and 0.57+/-0.06 mL g(-1) h(-1), respectively). The TNZ in helox, however, was shifted upwards by about 3 degrees C. Below the TNZ, sugar gliders were able to withstand an effective temperature of -24.7+/-7.3 degrees C with an HP(max) of 3.14+/-0.36 mL g(-1) h(-1). The low effective temperature tolerated by sugar gliders shows that they are competent thermoregulators despite their apparent lack of functional brown fat. Similarities of BMRs in air and helox suggest that the effect of helox is restricted to an increase of heat loss, and, consequently, helox represents a useful tool for thermal physiologists. Moreover, the lack of increase of BMR in helox despite an increase in thermal conductance of sugar gliders suggests that BMR is not a function of body surface.

Flexibility in basal metabolic rate and evaporative water loss among hoopoe larks exposed to different environmental temperatures.

The 'energy demand' hypothesis for short-term adjustments in basal metabolic rate (BMR) posits that birds adjust the size of their internal organs relative to food intake, a correlate of energy demand. We tested this hypothesis on hoopoe larks (Alaemon alaudipes), inhabitants of the Arabian desert, by acclimating birds for 3 weeks at 15 degrees C and at 36 degrees C, then measuring their BMR and total evaporative water loss (TEWL). Thereafter, we determined the dry masses of their brain, heart, liver, kidney, stomach, intestine and muscles of the pectoral region. Although mean body mass did not differ initially between the two groups, after 3 weeks, birds in the 15 degrees C group had gained mass (44.1+/-6.5 g), whereas larks in the 36 degrees C group had maintained a constant mass (36.6+/-3.6 g; means +/- s.d., N=6). Birds in the 15 degrees C group had a mean BMR of 46.8+/-6.9 kJ day(-1), whereas birds in the 36 degrees C group had a BMR of 32.9+/-6.3 kJ day(-1), values that were significantly different when we controlled for differences in body mass. When measured at 35 degrees C, larks in the cold-exposure group had a TEWL of 3.55+/-0.60 g H(2)O day(-)(1), whereas TEWL for birds in the 36 degrees C group averaged 2.23+/-0.28 g H(2)O day(-1), a difference of 59.2%. Mass-independent TEWL differed significantly between groups. Larks in the 15 degrees C group had a significantly larger liver, kidney and intestine than larks in the 36 degrees C group. The total increase in organ mass contributed 14.3% towards the total mass increment in the cold exposure group. Increased food intake among larks in the cold group apparently resulted in enlargement of some of the internal organs, and the increase in mass of these organs required a higher rate of oxygen uptake to support them. As oxygen demands increased, larks apparently lost more evaporative water, but the relationship between increases in BMR and TEWL remains unresolved.

Total energy expenditure in the elderly.

Chronic diseases and disabilities increase with age, affecting more than 60% of those over 75 y, and limiting activities in about half of them. Therefore, total energy expenditure (TEE) and its components are assessed separately in health and disease. An analysis of 568 doubly labelled water measurements in 'healthy' subjects (184 measurements in subjects over 65 years) suggests that there is a decrease of 0.69 and 0.43 MJ/day/decade respectively in men (standard weight 75 kg) and women (standard weight 67 kg). Physical activity (PA) accounted for 46% of the decrease in TEE, basal metabolic rate (BMR) for 44% of the decrease and thermogenesis (T) for the remaining 10%. TEE was found to be 10.79+/-2.09 and 8.62+/-1.49 MJ/day in 150 men and 100 women aged over 60 y, respectively. Of the total variance in TEE, measured with doubly labelled water over a 2 week period, 69% was considered to be due to differences between individuals, and 31% to differences within individuals. The variance due to PA plus T was threefold greater than that due to BMR. Physiological factors were far more important than methodological factors in influencing measurements of TEE, BMR and PA+T. An analysis of 136 measurements of TEE (doubly labelled water and bicarbonate-urea methods) in free-living elderly patients suffering from a variety of diseases suggests a frequent decrease in TEE, which may occur despite an increase in BMR. This is largely due to a reduction is PA (eg up to approximately 50% reduction), but in some cases it is also due to a reduction in BMR (loss of body weight). More comprehensive information is required about TEE and its components, partly because of a probable selection bias in recruitment of subjects participating in specific tracer studies, and partly because of the variable effects of different diseases and factors that operate at different times in the course of the same disease.

Mechanisms of changes in basal metabolism during ageing.

A considerable number of physiological functions are known to show a gradual decline with increasing age. However, the effects of ageing differ widely between organ systems. It is believed that basal metabolic rate (BMR) falls dramatically with age. These observations, largely based on cross-sectional surveys, are discussed in light of our present understanding of the biology of ageing. This paper reviews both the longitudinal and cross-sectional studies of BMR and presents evidence that the fall in BMR with ageing may be less dramatic than previously perceived. Indeed, some subjects may show an increase in BMR with ageing. The mechanism of changes in BMR during ageing will be discussed. Organ weight changes appear to have a profound impact on BMR. The use of BMR to predict total energy expenditure in the 'old elderly' (>75 y) is unlikely to be of any practical use due to wide intra- and inter-individual variation in BMR. This wide intra- and inter-individual variation in BMR is due to illness, disease and other metabolic disorders seen in the elderly. Finally, the importance of measuring BMR in elderly populations for its use in clinical medicine will be discussed.

Energy expenditure in disease: time to revisit?

Knowledge of energy expenditure is especially important in disease, and may in fact help in the understanding of the pathophysiology of wasting associated with disease. Energy requirements in a clinical setting are often 'prescribed' by health professionals, either directly through enteral or parenteral feeding, or perhaps controlled through a hospital diet. Studies initially suggested an increase in energy expenditure, and thus energy requirements, as a direct result of an increase in basal metabolic rate often seen in disease. However, many problems exist in the measurement of BMR in a disease situation, due to the effects of drugs, clinical practice, feeding or possibly anxiety either as a cause of the disease or the measurement itself. These problems could in themselves contribute to the rise in metabolism seen in disease. More recently, however, with the use of tracer techniques such as doubly-labelled water and the bicarbonate-urea method, more accurate estimates of energy expenditure, and thus energy requirements, have been made. Some such measurements have in fact shown that even with an elevated BMR, free-living total energy expenditure can in fact be reduced in many disease situations, suggesting a reduced rather than an increased energy requirement. The present review investigates measurements of total energy expenditure in disease to explore the hypothesis that energy expenditure in disease, even with an elevated BMR, can in fact be reduced due to a concurrent reduction in physical activity.

Women at altitude: energy requirement at 4,300 m.

To test the hypotheses that prolonged exposure to moderately high altitude increases the energy requirement of adequately fed women and that the sole cause of the increase is an elevation in basal metabolic rate (BMR), we studied 16 healthy women [21.7 +/- 0.5 (SD) yr; 167.4 +/- 1.1 cm; 62.2 +/- 1.0 kg]. Studies were conducted over 12 days at sea level (SL) and at 4,300 m [high altitude (HA)]. To test that menstrual cycle phase has an effect on energetics at HA, we monitored menstrual cycle in all women, and most women (n = 11) were studied in the same phase at SL and HA. Daily energy intake at HA was increased to respond to increases in BMR and to maintain body weight and body composition. Mean BMR for the group rose 6.9% above SL by day 3 at HA and fell to SL values by day 6. Total energy requirement remained elevated 6% at HA [ approximately 670 kJ/day (160 kcal/day) above that at SL], but the small and transient increase in BMR could not explain all of this increase, giving rise to an apparent "energy requirement excess." The transient nature of the rise in BMR may have been due to the fitness level of the subjects. The response to altitude was not affected by menstrual cycle phase. The energy requirement excess is at present unexplained.

Outdoor wintering of suckler cows in low mountain ranges

The aim of the present investigation was to study the adaptability of beef cows to outdoor wintering. Between 1992 and 1996, spring-calving suckler cows were observed during four winter periods in a low mountain range area. Cows of the Galloway and Limousin×Friesian genotypes were used. Two reference herds consisted of outdoor-wintered Galloway cows with access to a roofed area (Gal-Roof) and Limousin×Friesian cows kept in an uninsulated barn (LF-Barn) and were considered to reflect typical German suckler cow systems. As an experimental herd, Limousin×Friesian cows were wintered outdoors with access to a roofed area during the first three winter periods (LF-Roof) and in the last winter, these cows had no access to a roofed area (LF-No Roof). On uninsulated ground, the percentage of lying cows decreased and cows preferred to lie on a straw-bedded yard when the ambient temperature was low and the ground was moist. When cows had a choice between different weather-protected areas, the roofed area was most frequently visited. But Limousin×Friesian cows without access to a roofed area did not suffer from hypothermia when dry lying areas were provided. In severe weather conditions, cows reduced their motor activity and remained near the feeding point which could have an adverse influence on the environment. The body condition scores at the end of winter indicated that the outdoor-wintered cows were in similar body condition to cows kept indoors which meant that the expected increase in basal metabolic rate was not high. Continuous recording of vaginal temperature during the winter period showed that, even in severe weather conditions, cows were able to maintain homeothermy. Even in a low mountain range area there was no evidence of Galloway cows being more cold tolerant than Limousin×Friesian cows and outdoor wintering of both genotypes was possible.

Peroxisome proliferators as adjuvants for the reverse-electron-transport therapy of obesity: an explanation for the large increase in metabolic rate of MEDICA 16-treated rats

The efficacy of reverse-electron-transport therapy of obesity should be promoted by agents which up-regulate hepatocyte enzymes that are potentially rate-limiting for mitochondrial fatty acid oxidation and electron shuttles. Peroxisome proliferator drugs, including the fibrates used to treat hyperlipidemia, may be useful in this regard, as they induce malic enzyme, the mitochondrial glycerol-3-phosphate dehydrogenase, and carnitine palmitoyl transferase I in rodent hepatocytes. An agent of this class, MEDICA 16, has the additional property of potently inhibiting both citrate lyase and acetyl-CoA carboxylase. As a result, me thyl-substituted di a ca rboxylic acids (MEDICA) 16 can be expected to disinhibit hepatic fatty acid oxidation while up-regulating electron shuttle mechanisms, and thus should stimulate reverse electron transport. This may explain the remarkable 40% increase in basal metabolic rate observed in normal rats ingesting MEDICA 16 – an effect not associated with any compensatory increase in food intake. Relative to controls, the MEDICA 16-treated rats achieved a 50% reduction in body fat and a modest increase in lean mass, such that weight and growth were not changed. In other rodent strains, MEDICA 16 has prevented obesity diabetes and atherogenesis. However, whether MEDICA 16 and other peroxisome proliferator drugs will have clinical utility in reverse-electron-transport therapy may hinge on their ability to induce key enzymes inhuman hepatocytes; cell culture studies to evaluate this are required.

Mahogany ( mg ) stimulates feeding and increases basal metabolic rate independent of its suppression of agouti

The mahogany (mg) locus originally was identified as a recessive suppressor of agouti, a locus encoding a skin peptide that modifies coat color by antagonizing the melanocyte-stimulating hormone receptor or MC1-R. Certain dominant alleles of agouti cause an obesity syndrome when ectopic expression of the peptide aberrantly antagonizes the MC4-R, a related melanocyte-stimulating hormone receptor expressed in hypothalamic circuitry and involved in the regulation of feeding behavior and metabolism. Recent work has demonstrated that mg, when homozygous, blocks not only the ability of agouti to induce a yellow coat color when expressed in the skin of the lethal yellow mouse (AY), but also the obesity resulting from ectopic expression of agouti in the brain. Detailed analysis of mg/mg AY/a animals, presented here, demonstrates that mg/mg blocks the obesity, hyperinsulinemia, and increased linear growth induced by ectopic expression of the agouti peptide. Remarkably, however, mg/mg did not reduce hyperphagia in the AY/a mouse. Furthermore, mg/mg induced hyperphagia and an increase in basal metabolic rate in the C57BL/6J mouse in the absence of AY. Consequently, although mahogany is broadly required for agouti peptide action, it also appears to be involved in the control of metabolic rate and feeding behavior independent of its suppression of agouti.

Two-Month Treatment of Obese Subjects with the Oral Growth Hormone (GH) Secretagogue MK-677 Increases GH Secretion, Fat-Free Mass, and Energy Expenditure1

Obesity is associated with blunted GH secretion, unfavorable body composition, and increased cardiovascular mortality. The objective of this study was to investigate the effects of oral treatment with the GH secretagogue MK-677 on GH secretion and body composition in otherwise healthy obese males. The study was randomized, double blind, parallel, and placebo controlled. Twenty-four obese males, aged 18-50 yr, with body mass indexes greater than 30 kg/m2 and waist/hip ratios greater than 0.95, were treated with MK-677 25 mg (n = 12) or placebo (n = 12) daily for 8 weeks. Serum insulin-like growth factor I (IGF-I) increased approximately 40% with MK-677 treatment (P < 0.001 vs. placebo). Serum IGF-binding protein-3 was also significantly increased (P < or = 0.001 vs. placebo). GH and PRL (peak and area under the curve values) were significantly increased after the initial dose of MK-677. Significant increases, with the exception of peak PRL, persisted at 2 and 8 weeks of treatment. The increases in GH and PRL after the initial dose were significantly greater than the increase seen after multiple doses. Serum and urinary concentrations of cortisol were not increased at 2 and 8 weeks (P = NS, vs. placebo). Fat-free mass increased significantly in the MK-677 treatment group when determined with dual energy x-ray absorptiometry (P < 0.01) or using a four-compartment model (P < 0.05). Total and visceral fat were not significantly changed with active therapy. The basal metabolic rate was significantly increased at 2 weeks of MK-677 treatment (P = 0.01) but not at 8 weeks (P = 0.1). Fasting concentrations of glucose and insulin were unchanged, whereas an oral glucose tolerance test showed impairment of glucose homeostasis at 2 and 8 weeks. We conclude that 2-month treatment with MK-677 in healthy obese males caused a sustained increase in serum levels of GH, IGF-I, and IGF-binding protein-3. The effects on cortisol secretion were transient. Changes in body composition and energy expenditure were of an anabolic nature, with a sustained increase in fat-free mass and a transient increase in basal metabolic rate. Further studies are needed to evaluate whether a higher dose of MK-677 or a more prolonged treatment period can promote a reduction in body fat.

A Single Bout of Concentric Resistance Exercise Increases Basal Metabolic Rate 48 Hours After Exercise in Healthy 59-77-year-old Men

It has been shown that basal metabolic rate (BMR) decreases with age. The extent to which some of the decrease can be reversed by exercise in older men and women is unclear. Resistance exercise has been shown to significantly increase muscle mass in older individuals, and because muscle is a highly active metabolic tissue there is potential to increase BMR as a secondary outcome to the training adaptation. Twelve healthy men aged 59-77 years performed single-leg knee extension exercise (right and left leg) and bench press lifts (16 sets, 10 reps/set with timed recovery between sets) at 75% of the individual's 3RM. Subjects only performed the concentric phase of the lift. BMR was measured on two separate occasions, once after a nonexercise control period and again 48 hrs after a bout of resistance exercise. BMR was significantly increased (p < .006) 48 hrs after exercise (EX) compared to control (CON) (284.0 +/- 34.0 vs 274.9 +/- 34.0 kJ/hr, respectively). Calculated over a 24-hour period, the energy expenditure corresponded to 1570 +/- 193 and 1627 +/- 193 kcal/24 hr (p < .0002) for the CON and EX measures, respectively. VO2 (L/min) was higher (p < .0002) 48 hrs after the EX bout compared to 48 hrs post-CON (0.232 +/- 0.03 vs 0.225 +/- 0.03 L/min, respectively). We conclude that in healthy 59-77-year-old men, an acute bout of resistance exercise causes a sustained increase in BMR that persists for up to 48 hours after exercise.