Decline In Metabolic Rate Research Articles

Development of ventilatory chemoreflexes in Coturnix quail chicks

Compared to mammals, little is known about the development of the respiratory control system in birds. In the present study, ventilation and metabolism were measured in Coturnix quail chicks exposed to room air, hypoxia (11 % O2), and hypercapnia (4% CO2) at 0–1, 3–4, and 6–7 days posthatching (dph). Mass-specific ventilation and metabolic rate tended to increase between 0–1 and 3–4 dph and then decrease again between 3–4 and 6–7 dph. The magnitude of the hypoxic ventilatory response (HVR) increased with age. The HVR also exhibited a biphasic shape in younger quail: after the initial increase in ventilation, ventilation declined back to (0–1 dph), or toward (4 dph), baseline. Older chicks (6–7 dph) had a “sustained HVR” in which ventilation remained high throughout the hypoxic challenge. The biphasic HVR did not appear to be caused by a decline in metabolic rate; although hypoxic hypometabolism was observed in quail chicks in all three age groups, the metabolic response appeared to occur more slowly than the biphasic HVR. The biphasic ventilatory response was also specific to hypoxia since the hypercapnic ventilatory response (HCVR) was characterized by a sustained increase in ventilation in all three age groups. The magnitude of the HCVR decreased with age. These results point to several similarities in the development of ventilatory chemorflexes between Coturnix quail and newborn mammals, including age-dependent (1) increases in the HVR, (2) transitions from a biphasic to a sustained HVR, and (3) decreases in the HCVR. Whether homologous mechanisms underlie these developmental changes remains to be determined.

A newly developed feeder and oxygen measurement system reveals the effects of aging and obesity on the metabolic rate of zebrafish.

Metabolic alterations are relevant for the aging process. Declining metabolic rate with age is a common future of many animals, but it is not well understood how it does so. Here, we used zebrafish as a model for understanding how metabolic changes occur during aging and the interaction between aging and obesity on the metabolic rate. The oxygen consumption rate (OCR) has been used as an index of metabolic processes; however, it is difficult to accurately evaluate OCR with movement being considered because zebrafish need to move freely during the OCR measurement. To measure metabolic rate with high accuracy and efficiency, we developed a method for simultaneously collecting data on sequential oxygen consumption and distance moved by zebrafish using optical dissolved-oxygen sensors and the EthoVision video-tracking system as well as an automatic feeding system for zebrafish whereby obese zebrafish were produced by short-term overfeeding treatment. Using these systems, we examined metabolic changes during aging and overfeeding. First, we used 1- to 22-month-old zebrafish to evaluate changes in metabolism during the aging process. Measurements of body mass and length showed that the growth of the body rarely continued beyond 6 months, at which point zebrafish reach adulthood. Spontaneous swimming activity peaked at approximately 6-10 months and declined thereafter. Metabolic rates at low movement dramatically dropped during the first 4 months and gradually decreased with age after 10 months. These data suggest that metabolic aging becomes evident at approximately 10-14 months and that the metabolic rate (low movement) is useful for the detection of age-related metabolic changes in zebrafish. Second, by short-term overfeeding treatment using the automatic feeding system, we found that overweight is a strong risk factor for the development of metabolic disorders in zebrafish, but there was no interaction between obesity and aging on the metabolic rate. Therefore, our data suggest that the aging-related decline in metabolic-rate may be mostly programmed rather than being affected by energy balance disorder.

Gut microbiota mediates the anti-obesity effect of calorie restriction in mice

Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.

Mitochondrial phenotype during torpor: Modulation of mitochondrial electron transport system in the Chilean mouse–opossum Thylamys elegans

Mammalian torpor is a phenotype characterized by a controlled decline of metabolic rate, generally followed by a reduction in body temperature. During arousal from torpor, both metabolic rate and body temperature rapidly returns to resting levels. Metabolic rate reduction experienced by torpid animals is triggered by active suppression of mitochondrial respiration, which is rapidly reversed during rewarming process. In this study, we analyzed the changes in the maximal activity of key enzymes related to electron transport system (complexes I, III and IV) in six tissues of torpid, arousing and euthermic Chilean mouse-opossums (Thylamys elegans). We observed higher maximal activities of complexes I and IV during torpor in brain, heart and liver, the most metabolically active organs in mammals. On the contrary, higher enzymatic activities of complexes III were observed during torpor in kidneys and lungs. Moreover, skeletal muscle was the only tissue without significant differences among stages in all complexes evaluated, suggesting no modulation of oxidative capacities of electron transport system components in this thermogenic tissue. In overall, our data suggest that complexes I and IV activity plays a major role in initiation and maintenance of metabolic suppression during torpor in Chilean mouse–opossum, whereas improvement of oxidative capacities in complex III might be critical to sustain metabolic machinery in organs that remains metabolically active during torpor.

Extreme longevity in a deep-sea vestimentiferan tubeworm and its implications for the evolution of life history strategies.

The deep sea is home to many species that have longer life spans than their shallow-water counterparts. This trend is primarily related to the decline in metabolic rates with temperature as depth increases. However, at bathyal depths, the cold-seep vestimentiferan tubeworm species Lamellibrachia luymesi and Seepiophila jonesi reach extremely old ages beyond what is predicted by the simple scaling of life span with body size and temperature. Here, we use individual-based models based on in situ growth rates to show that another species of cold-seep tubeworm found in the Gulf of Mexico, Escarpia laminata, also has an extraordinarily long life span, regularly achieving ages of 100-200years with some individuals older than 300years. The distribution of results from individual simulations as well as whole population simulations involving mortality and recruitment rates support these age estimates. The low 0.67% mortality rate measurements from collected populations of E. laminata are similar to mortality rates in L. luymesi and S. jonesi and play a role in evolution of the long life span of cold-seep tubeworms. These results support longevity theory, which states that in the absence of extrinsic mortality threats, natural selection will select for individuals that senesce slower and reproduce continually into their old age.

Contributors to Metabolic Disease Risk Following Spinal Cord Injury.

Spinal cord injury (SCI) induced changes in neurological function have significant impact on the metabolism and subsequent metabolic-related disease risk in injured individuals. This metabolic-related disease risk relationship is differential depending on the anatomic level and severity of the injury, with high level anatomic injuries contributing a greater risk of glucose and lipid dysregulation resulting in type 2 diabetes and cardiovascular disease risk elevation. Although alterations in body composition, particularly excess adiposity and its anatomical distribution in the visceral depot or ectopic location in non-adipose organs, is known to significantly contribute to metabolic disease risk, changes in fat mass and fat-free mass do not fully account for this elevated disease risk in subjects with SCI. There are other negative adaptations in body composition including reductions in skeletal muscle mass and alterations in muscle fiber type, in addition to significant reduction in physical activity, that contribute to a decline in metabolic rate and increased metabolic disease risk following SCI. Recent studies in adult humans suggest cold- and diet-induced thermogenesis through brown adipose tissue metabolism may be important for energy balance and substrate metabolism, and particularly sensitive to sympathetic nervous signaling. Considering the alterations that occur in the autonomic nervous system (SNS) (sympathetic and parasympathetic) following a SCI, significant dysfunction of brown adipose function is expected. This review will highlight metabolic alterations following SCI and integrate findings from brown adipose tissue studies as potential new areas of research to pursue.

As we grow old: nutritional considerations for older patients on dialysis.

The number of older people on dialysis is increasing, along with a need to develop specialized health care to manage their needs. Aging-related changes occur in physiological, psychosocial and medical aspects, all of which present nutritional risk factors ranging from a decline in metabolic rate to assistance with feeding-related activities. In dialysis, these are compounded by the metabolic derangements of chronic kidney disease (CKD) and of dialysis treatment per se, leading to possible aggravation of protein-energy wasting syndrome. This review discusses the nutritional derangements of the older patient on dialysis, debates the need for specific renal nutrition guidelines and summarizes potential interventions to meet their nutritional needs. Interdisciplinary collaborations between renal and geriatric clinicians should be encouraged to ensure better quality of life and outcomes for this growing segment of the dialysis population.

Mitochondrial phenotype of marsupial torpor: Fuel metabolic switch in the Chilean mouse-opossum Thylamys elegans.

Torpor is a phenotype characterized by a controlled decline of metabolic rate and body temperature. During arousal from torpor, organs undergo rapid metabolic reactivation and rewarming to near normal levels. As torpor progress, animals show a preference for fatty acids over glucose as primary source of energy. Here, we analyzed for first time the changes in the maximal activity of key enzymes related to fatty acid (Carnitine palmitoyltransferase and β-Hydroxyacyl CoA dehydrogenase) and carbohydrate (Pyruvate kinase, Phosphofructokinase and Lactate dehydrogenase) catabolism, as well as mitochondrial oxidative capacity (Citrate synthase), in six organs of torpid, arousing and euthermic Chilean mouse-opossums (Thylamys elegans). Our results showed that activity of enzymes related to fatty acid and carbohydrate catabolism were different among torpor phases and the pattern of variation differs among tissues. In terms of lipid utilization, maximal enzymatic activities differ in tissues with high oxidative capacity such as heart, kidney, and liver. In terms of carbohydrate use, lower enzymatic activities were observed during torpor in brain and liver. Interestingly, citrate synthase activity did not differ thought torpor-arousal cycle in any tissues analyzed, suggesting no modulation of mitochondrial content in T. elegans. Overall results provide an indication that modulation of enzymes associated with carbohydrate and fatty-acid pathways is mainly oriented to limit energy expensive processes and sustain energy metabolism during transition from torpor to euthermy. Future studies are required to elucidate if physiological events observed for T. elegans are unique from other marsupials, or represents a general response in marsupials. J. Exp. Zool. 325A:41-51, 2016. © 2015 Wiley Periodicals, Inc.

Immune response costs are associated with changes in resource acquisition and not resource reallocation

Summary Evolutionary ecologists frequently argue that parasite defence is costly because resources must be reallocated from other life‐history traits to fuel the immune response. However, this hypothesis is rarely explicitly tested. An alternative possibility is that immune responses impair an organism's ability to acquire the resources it needs to support metabolism. Here, we disentangle these opposing hypotheses for why the activation costs of parasite resistance arise. We studied fecundity costs associated with immune stimulation in Drosophila melanogaster. Then, by measuring correlated changes in metabolic rate, food consumption and body weight, we assessed whether responses were consistent with immunity costs originating from altered resource allocation or from impaired resource acquisition. Microbial injection resulted in a 45% fecundity decrease. It also triggered a mean decline in metabolic rate of 6% and a mean reduction in food intake of 31%; body weight was unaffected. Metabolic rate downregulation was greater in males than in females, whereas declines in food ingestion were of similar magnitude in both sexes. These physiological shifts did not depend on whether microbial challenges were alive or dead, thus they resulted from immune system activation not pathogenesis. These costs of immune activation are significant for individuals that successfully resist infection and might also occur in other situations when immune responses are upregulated without infection. Whilst we found significant activation costs of resistance, our data provide no compelling evidence for the popularly argued hypothesis that immune deployment is costly because of reallocation of energetic resources to the immune system. Instead, reduction in resource acquisition due to ‘infection‐induced anorexia’ may be the principal driver of metabolic changes and fecundity costs resulting from immune response activation.

Is there metabolic cold adaptation in terrestrial ectotherms? Exploring latitudinal compensation in the invasive snail Cornu aspersum.

Lower temperatures, extreme seasonality and shorter growing seasons at higher latitudes are expected to cause a decline in metabolic rates and annual growth rates of ectotherms. If a reduction in the rates of these biological processes involves a reduction in fitness, then organisms may evolve compensatory responses for the constraints imposed by high-latitude habitats. To test the existence of a latitudinal compensation in ectotherms, we used a common-garden experiment to investigate the extent to which the level of energy turnover (measured as standard metabolic rate, SMR) and the energy budget (energy allocation to growth) are affected by climatic constraints in three populations of the land snail Cornu aspersum, distributed across a latitudinal gradient of 1300 km in Chile. Our results did not support the existence of a latitudinal compensation in metabolic rates (metabolic cold adaptation). However, there was a countergradient variation (CnGV) for growth rate in which the highest latitudinal population exhibited greater growth rates than their counterparts from lower latitudes. Surprisingly, this CnGV pattern was accompanied by a lower apparent dry-matter digestibility, which could highlight a differential assimilation of ingested nutrients into somatic tissue, revealing enhanced growth efficiency in snails from the highest latitudinal habitat. Our evidence highlights that adjustments in energy allocation to the digestive machinery and to protein storage could act as a latitudinal compensation for enhanced growth efficiency in snails from the highest latitudinal population.

Metabolic regulatory clues from the naked mole rat: Toward brain regulatory functions during stroke

Resistance to tissue hypoxia is a robust fundamental adaptation to low oxygen supply, and represents a novel neuroscience problem with significance to mammalian physiology as well as human health. With the underlying mechanisms strongly conserved in evolution, the ability to resist tissue hypoxia in natural systems has recently emerged as an interesting model in mammalian physiology research to understand mechanisms that can be manipulated for the clinical management of stroke. The extraordinary ability to resist tissue hypoxia by the naked mole rat (NMR) indicates the presence of a unique mechanism that underlies the remarkable healthy life span and exceptional hypoxia resistance. This opens an interesting line of research into understanding the mechanisms employed by the naked mole rat (Heterocephalus glaber) to protect the brain during hypoxia. In a series of studies, we first examined the presence of neuroprotection in the brain cells of naked mole rats (NMRs) subjected to hypoxic insults, and then characterized the expression of such neuroprotection in a wide range of time intervals. We used oxygen nutrient deprivation (OND), an in vitro model of resistance to tissue hypoxia to determine whether there is evidence of neuronal survival in the hippocampal (CA1) slices of NMRs that are subjected to chronic hypoxia. Hippocampus neurons of NMRs that were kept in hypoxic condition consistently tolerated OND right from the onset time of 5h. This tolerance was maintained for 24h. This finding indicates that there is evidence of resistance to tissue hypoxia by CA1 neurons of NMRs. We further examined the effect of hypoxia on metabolic rate in the NMR. Repeated measurement of metabolic rates during exposure of naked mole rats to hypoxia over a constant ambient temperature indicates that hypoxia significantly decreased metabolic rates in the NMR, suggesting that the observed decline in metabolic rate during hypoxia may contribute to the adaptive mechanism used by the NMR to resist tissue hypoxia. This work is aimed to contribute to the understanding of mechanisms of resistance to tissue hypoxia in the NMR as an important life-sustaining process, which can be translated into therapeutic interventions during stroke.

Impact of different acclimation temperatures and duration on the chill coma temperature and oxygen consumption in the tenebrionid beetleAlphitobius diaperinus

When the ambient temperature is lowered to an insect's lower thermal limit, the insect enters into chill coma. Chill coma temperature and chill coma recovery can vary within species as a result of thermal acclimation, although the physiological basis of the onset of chill coma remains poorly understood. The present study investigates how the temperature of acclimation (0, 5, 10, 15 and 20 °C for 2 or 7 days) affects chill coma temperature and oxygen consumption in adultAlphitobius diaperinusPanzer (Coleoptera: Tenebrionidae). It is hypothesized that the threshold decline in metabolic rate corresponds to the entry into chill coma. Oxygen consumption (as a proxy of metabolism) is measured across the chill coma temperature threshold, and a strong decline in oxygen consumption is expected at entry into chill coma. The acclimation decreases the chill coma temperature significantly from 6.6 ± 1.1 °C in control insects to 3.1 ± 0.7 °C in those acclimated to 10 °C. The change in metabolic rate (Q10) after acclimation to temperatures ranging from 10 to 20 °C is 3.7. Despite acclimation, the metabolic rate ofA. diaperinusconforms to Arrhenius kinetics, suggesting that the response of this beetle does not show metabolic compensation. The data suggest the existence of a threshold decline in metabolic rate during cooling that coincides with the temperature at which an insect goes into chill coma.

A 5-month weight-reduction programme has a positive effect on body composition, aerobic fitness, and habitual physical activity of severely obese girls: A pilot evaluation study

In this pilot study, we wished to determine whether a 5-month multidisciplinary programme of a combined dietary-nutritional education-exercise intervention would have favourable effects on the health status of 18 obese adolescent girls. Before and after the clinical intervention, body composition and habitual physical activity were assessed by bioelectrical impedance and accelerometry, respectively. Aerobic fitness and substrate utilization were determined by gas exchange using an incremental field test that mimics habitual conditions. Despite a significantly (P < 0.001) greater loss of fat mass (−8.7 ± 4.1 kg) compared with fat-free mass (−2.8 ± 2.2 kg), energy expenditure at rest decreased by 9% following the intervention. Maximal oxygen consumption ([Vdot]O2max) related to fat-free mass increased by 7% (P < 0.05), whereas substrate utilization during exercise did not change following the intervention. Moderate and intense physical activity increased by 15% (+20 min · day−1; P < 0.05) and 45% (+25 min · day−1; P < 0.01), respectively. A significant relationship was observed between change in habitual physical activity and change in [Vdot]O2max/fat-free mass (r = 0.56, P = 0.01). The present multidisciplinary programme enhanced the loss of fat mass relative to fat-free mass but not sufficiently so to prevent a decline in metabolic rate during rest. Our results suggest a coupling in the improvement of aerobic fitness and habitual physical activity in obese adolescent girls, and hence an improvement in behaviour in relation to physical activity.

N-specific metabolic data are not relevant to the ‘visual interactions’ hypothesis concerning the depth-related declines in metabolic rates: Comment on Ikeda et al. (2006)

Ikeda et al. (2006; Mar Ecol Prog Ser 322:199-211) declared that they were testing the 'visual interactions' hypothesis for the decline in metabolic rates with depth in midwater animals, but their data and data analysis are irrelevant to this hypothesis for 4 reasons: (1) they do not show changes relative to the live mass of the animals studied; (2) they do not compare species-specific data; (3) they do not use evolutionarily significant descriptors of habitat depth; and (4) there are significant differences in the respirometry methods within their own data sets, and between those data and the data that support the 'visual interactions' hypothesis. Live weight mass-specific expression of rates is necessary when considering hypotheses concerning the evolution and function of living animals, although N-specific expressions may be useful in other contexts.

A Controlled Pharmacogenetic Trial of Sibutramine on Weight Loss and Body Composition in Obese or Overweight Adults

Weight loss in response to sibutramine is highly variable. We assessed the association of specific markers of polymorphisms of candidate alpha2A adrenoreceptor, 5-HT transporter, and GNbeta3 genes and weight loss with sibutramine. We conducted a randomized, double-blind, pharmacogenetic study of behavioral therapy and sibutramine (10 or 15 mg daily) or placebo for 12 weeks in 181 overweight or obese participants. We measured body weight, body mass index, body composition, gastric emptying, and genetic variation (alpha2A C1291G, 5-HTTLPR, and GNbeta3 C825T genotypes). Analysis of covariance was used to assess treatment effects on and associations of the specific markers of candidate genes with weight loss and body composition. Sibutramine, 10 and 15 mg, caused weight loss (P = .009); there was a statistically significant gene by dose interaction for GNbeta3 genotype. For each candidate gene, significant treatment effects at 12 weeks were observed (P < .017) for all specific genotype variants (Delta weight loss in the 2 sibutramine doses vs placebo): alpha2A CC (Delta, approximately 5 kg), GNbeta3 TC/TT (Delta, approximately 6 kg), and 5-HTTLPR LS/SS (Delta, approximately 4.5 kg). Gene pairs resulted in significantly greater sibutramine treatment effects on weight (both P < .002): in participants with 5-HTTLPR LS/SS with GNbeta3 TC/TT; Delta, approximately 6 kg and those with alpha2A CC with GNbeta3 TC/TT; Delta, approximately 8 kg; however, effects were not synergistic. Treatment with sibutramine also resulted in significantly greater reduction of body fat for specific alpha2A CC and GNbeta3 TC/TT genotype variants individually (both P < .02). Patient selection based on candidate genes may enhance response to multidimensional sibutramine and behavioral therapy for obesity.

Restoration of fasting‐induced torpor in dopamine beta hydoxylase −/− mice

Many organisms throughout the animal kingdom, including mice, can experience a well‐orchestrated decline in metabolic rate and core body temperature (Tb) in response to, or in anticipation of, a lack of sufficient caloric intake. Previous investigations have shown that the adipocyte‐derived hormone leptin can blunt or even prevent these bouts of torpor. Unlike wildtype counterparts, mice deficient in the enzyme dopamine β hydroxylase (Dbh −/− mice), which are unable to synthesize epinephrine and norepinephrine, do not reduce circulating leptin upon fasting nor do they enter torpor. To test the hypothesis that the onset of torpor bouts in mice during a fast requires sympathetically‐mediated reduction in circulating leptin, mice deficient in both leptin and the enzyme dbh (DBL KO) were generated. Both ob/ob mice, which are deficient in leptin, and the DBL KO mice were obese at 6 months of age (approximately 60 grams) and ate 60% more food (5 grams per day vs. 3 grams per day for counterparts). This suggests that Epi and NE play little role in the mechanism of leptin‐deficient obesity. Upon fasting, wildtype and ob/ob mice entered torpor as assessed by telemetric core Tb acquisition (WT min Tb = 23.9 ± 0.4: ob/ob min Tb = 23.8 ± 0.4 C), whereas the length of torpor was significantly longer in ob/ob mice vs. WT (633 ± 53 vs. 359 ± 35 minutes, respectively). Both ob/ob and WT mice entered torpor about 7 hours after initiation of the fast. As we have seen previously Dbh −/− mice did not enter torpor with fasting. The DBL KO mice entered torpor upon fasting (min. Tb = 24.3 ± 0.4 C), did so within the first 30 minutes of fasting, and remained in the torpor bout twice as long as ob/ob mice (1155 ± 42 minutes). These data are consistent with our hypothesis that sympathetic activation of white fat is required for the onset of torpor, and that catecholamines are important in recovery from a bout of torpor.

Rates of ethanol metabolism decrease in sons of alcoholics following a priming dose of ethanol

Rapid changes in rates of ethanol metabolism in response to acute ethanol administration have been observed in animals and humans. To examine whether this phenomenon might vary by risk for alcoholism, 23 young men with a positive family history of alcoholism (family history positive [FHP]) were compared to 15 young men without a family history of alcoholism (family history negative [FHN]). Rates of ethanol metabolism were measured in all subjects first after an initial ethanol dose (0.85 g/kg) and then, several hours later, a second dose (0.3 g/kg), and the two rates were compared. The two groups of subjects were similar in their histories of ethanol consumption. FHP subjects demonstrated faster initial rates of ethanol metabolism, 148 ± 36 mg/kg/h, compared to FHN subjects, 124 ± 18 mg/kg/h, P = .01. However, FHN subjects increased their rate of metabolism by 10 ± 27% compared to a decrease of −15 ± 24% in FHP subjects, P = .007. Fifty-two percent of the FHP and none of the FHN subjects exhibited a decline in metabolic rate of 20% or more, P = .0008. Since a significant proportion of FHP subjects exhibited a decrease in the second rate of ethanol metabolism, these preliminary data might help to partly explain why FHP individuals differ in their sensitivity to ethanol and are more likely to develop alcohol dependence.

Serotonin and Norepinephrine Reuptake Inhibition and Eating Behavior

Brain neurotransmitters, serotonin and norepinephrine, play an important role in the central nervous control of energy balance and are involved in symptomatology related to both obesity and depression. Therefore both serotonin and norepinephrine neural pathways have been paid a special attention as targets for the antiobesity drugs, antidepressants, and drugs used in the treatment of eating disorders. Selective serotonin reuptake inhibitors (SSRI) have been used in the treatment of depression and eating disorders but have failed to achieve sustained weight loss in the treatment of obesity. Sibutramine, a serotonin and norepinephrine reuptake inhibitor, which induces satiety and prevents decline in metabolic rate associated with a hypocaloric diet, is currently the sole centrally acting drug indicated for the long-term treatment of obesity. Depression, dietary disinhibition (evaluated by the Eating Inventory [EI]), and stress are associated with the accumulation of abdominal fat and the development of metabolic syndrome and related diseases. Subjects with abdominal obesity demonstrate neuroendocrine abnormalities which result in disturbances in hypothalamo-pituitary-adrenal (HPA) function. Treatment with SSRI might interrupt the vicious circle which leads to endocrine abnormalities and the accumulation of abdominal fat. Obesity treatment with sibutramine results, not only in significant weight loss, but also in reduction of abdominal fat and in the improvement of health risks associated with metabolic syndrome (lipid profile, blood glucose, insulin, HbA1c, and uric acid), as well as in the decline in disinhibition score of the EI. In a 1-year sibutramine trial, only a decrease in the disinhibition score remained a significant correlate of weight loss among the psychobehavioral and nutritional factors which were taken into account.

Water conservation in fasting northern elephant seals (Mirounga angustirostris).

Prolonged terrestrial fasting is a key element in the life history of elephant seals. While on land seals typically fast without access to fresh water, and thus must maintain positive water balance by reductions in water loss such that they can subsist primarily on metabolic water production (MWP). The terrestrial apnea demonstrated by seals may reduce respiratory evaporative water loss (REWL) to levels that allow seals to make a net gain of water from MWP. We empirically measured REWL in 13 fasting northern elephant seal pups and determined the effects on water conservation of a breathing mode that incorporates a regular pattern of apneas, of > or =1 min in duration, followed by eupneic recovery, compared with a breathing mode with no apneas longer than 20 s and resembling typical breathing patterns in other mammals (normative breathing). Overall REWL fell 41% from 0.075+/-0.013 g min(-1) (mean +/- s.d.) during normative breathing to 0.044+/-0.006 g min(-1) during apneic breathing. The decline in REWL is attributed to a decrease in overall ventilation rate, made possible by a decline in metabolic rate along with an increase in oxygen extraction that would occur during apneic breathing. Data on the range of ambient humidity conditions at the local breeding site were collected and used to bound the range of environmental conditions used in laboratory measurements. Our data showed that the observed variations in ambient humidity had no significant effect on REWL. A combination of apneic breathing and the complex nasal turbinates allows fasting elephant seals to reduce REWL well below the rate of MWP so that they can maintain water balance during the fast.

Electron microscopy and microcalorimetry of the postnatal rat heart ( Rattus norvegicus)

The interplay of ultrastructure and tissue metabolism was examined in neonatal, infant and adult rat hearts by electron microscopy and microcalorimetry. Morphometry was used to determine parameters of oxygen diffusion capacity (distance between capillaries and mitochondria, capillary surface density) and oxidative metabolic capacity (mitochondrial volume fraction). Thin slices and large samples of living tissue were examined calorimetrically to quantify aerobic metabolism and ischemia tolerance, respectively. After birth, rat hearts grow in parallel to body mass and show characteristics of cellular hypertrophy. Capillary surface density increases from neonatal to infant rats, and decreases to an intermediate value in adult rats. The distance between capillaries and mitochondria shows no significant changes throughout postnatal development. Mitochondrial volume fraction increases continuously until adulthood. The specific aerobic tissue metabolic rate is higher in the neonatal than in the infant and adult rat. However, the ischemic decline in metabolic rate is much slower in the neonatal rat, reflecting an elevated hypoxia tolerance. In conclusion, the neonatal rat heart exhibits a high metabolic rate despite a low mitochondrial volume fraction. The subsequent structural rearrangements can be interpreted as long-term adaptations to the increased postnatal workload and may contribute to the progressive loss of hypoxia tolerance.