Changes In Energy Expenditure Research Articles

Weight loss does not affect the sit-to-stand metabolic cost in adolescents with obesity.

There is considerable interest in simple and effective methods to reduce sitting time and increase energy expenditure, and standing breaks have emerged as a realisable approach in individuals with obesity. The aim of the present study was to determine the extent to which energy expenditure in standing differs from sitting, and whether this energetic and metabolic-related responses are modified following a weight loss program in adolescents with obesity. After body composition assessment (DXA), cardiorespiratory and metabolic variables were continuously recorded (indirect calorimetry) during 10min while sitting and then during 5min standing posture before (n = 21; T1) and at the end of a multidisciplinary intervention (n = 17; T2) in adolescents with obesity. Before and after the intervention, energy expenditure and fat oxidation rates were significantly increased in standing compared with sitting. Weight loss did not change the relationship between sitting and standing energy expenditure. Sitting energy expenditure represented 1.0 and 1.1 Metabolic Equivalent of Task at T1 and T2, and increased to 1.1 and 1.2 during standing at T1 and T2, respectively. The percentage of change of android fat mass between T1 and T2 was positively associated with the percentage of change in energy expenditure from sitting to standing at T2. The vast majority of the adolescents with obesity significantly increased their energy expenditure between sitting and standing, both before and after a weight loss intervention. However, the standing posture did not allow breaking the sedentary threshold. Abdominal fat mass is associated with energic profile.

Host-diet-gut microbiome interactions influence human energy balance: a randomized clinical trial

The gut microbiome is emerging as a key modulator of human energy balance. Prior studies in humans lacked the environmental and dietary controls and precision required to quantitatively evaluate the contributions of the gut microbiome. Using a Microbiome Enhancer Diet (MBD) designed to deliver more dietary substrates to the colon and therefore modulate the gut microbiome, we quantified microbial and host contributions to human energy balance in a controlled feeding study with a randomized crossover design in young, healthy, weight stable males and females (NCT02939703). In a metabolic ward where the environment was strictly controlled, we measured energy intake, energy expenditure, and energy output (fecal and urinary). The primary endpoint was the within-participant difference in host metabolizable energy between experimental conditions [Control, Western Diet (WD) vs. MBD]. The secondary endpoints were enteroendocrine hormones, hunger/satiety, and food intake. Here we show that, compared to the WD, the MBD leads to an additional 116 ± 56 kcals (P < 0.0001) lost in feces daily and thus, lower metabolizable energy for the host (89.5 ± 0.73%; range 84.2-96.1% on the MBD vs. 95.4 ± 0.21%; range 94.1-97.0% on the WD; P < 0.0001) without changes in energy expenditure, hunger/satiety or food intake (P > 0.05). Microbial 16S rRNA gene copy number (a surrogate of biomass) increases (P < 0.0001), beta-diversity changes (whole genome shotgun sequencing; P = 0.02), and fermentation products increase (P < 0.01) on an MBD as compared to a WD along with significant changes in the host enteroendocrine system (P < 0.0001). The substantial interindividual variability in metabolizable energy on the MBD is explained in part by fecal SCFAs and biomass. Our results reveal the complex host-diet-microbiome interplay that modulates energy balance.

A long-acting GDF15 analog causes robust, sustained weight loss and reduction of food intake in an obese nonhuman primate model.

Growth Differentiation Factor-15 (GDF15) is a circulating polypeptide linked to cellular stress and metabolic adaptation. GDF15's half-life is ~3 h and activates the glial cell line-derived neurotrophic factor family receptor alpha-like (GFRAL) receptor expressed in the area postrema. To characterize sustained GFRAL agonism on food intake (FI) and body weight (BW), we tested a half-life extended analog of GDF15 (Compound H [CpdH]) suitable for reduced dosing frequency in obese cynomolgus monkeys. Animals were chronically treated once weekly (q.w.) with CpdH or long-acting GLP-1 analog dulaglutide. Mechanism-based longitudinal exposure-response modeling characterized effects of CpdH and dulaglutide on FI and BW. The novel model accounts for both acute, exposure-dependent effects reducing FI and compensatory changes in energy expenditure (EE) and FI occurring over time with weight loss. CpdH had linear, dose-proportional pharmacokinetics (terminal half-life ~8 days) and treatment caused exposure-dependent reductions in FI and BW. The 1.6 mg/kg CpdH reduced mean FI by 57.5% at 1 week and sustained FI reductions of 31.5% from weeks 9-12, resulting in peak reduction in BW of 16 ± 5%. Dulaglutide had more modest effects on FI and peak BW loss was 3.8 ± 4.0%. Longitudinal modeling of both the FI and BW profiles suggested reductions in BW observed with both CpdH and dulaglutide were fully explained by exposure-dependent reductions in FI without increase in EE. Upon verification of the pharmacokinetic/pharmacodynamic relationship established in monkeys and humans for dulaglutide, we predicted that CpdH could reach double digit BW loss in humans. In summary, a long-acting GDF15 analog led to sustained reductions in FI in overweight monkeys and holds potential for effective clinical obesity pharmacotherapy.

High-Intensity Interval Training Induces Protein Lactylation in Different Tissues of Mice with Specificity and Time Dependence

Protein lysine lactylation (Kla) is a novel protein acylation reported in recent years, which plays an important role in the development of several diseases with pathologically elevated lactate levels, such as tumors. The concentration of lactate as a donor is directly related to the Kla level. High-intensity interval training (HIIT) is a workout pattern that has positive effects in many metabolic diseases, but the mechanisms by which HIIT promotes health are not yet clear. Lactate is the main metabolite of HIIT, and it is unknown as to whether high lactate during HIIT can induce changes in Kla levels, as well as whether Kla levels differ in different tissues and how time-dependent Kla levels are. In this study, we observed the specificity and time-dependent effects of a single HIIT on the regulation of Kla in mouse tissues. In addition, we aimed to select tissues with high Kla specificity and obvious time dependence for lactylation quantitative omics and analyze the possible biological targets of HIIT-induced Kla regulation. A single HIIT induces Kla in tissues with high lactate uptake and metabolism, such as iWAT, BAT, soleus muscle and liver proteins, and Kla levels peak at 24 h after HIIT and return to steady state at 72 h. Kla proteins in iWAT may affect pathways related to glycolipid metabolism and are highly associated with de novo synthesis. It is speculated that the changes in energy expenditure, lipolytic effects and metabolic characteristics during the recovery period after HIIT may be related to the regulation of Kla in iWAT.

0002 Impact of Acute, Isocaloric Time-Restricted Eating on Resting Metabolic Rate and Obesogenic Factors in Healthy Lean Adults

Abstract Introduction Time-restricted eating (TRE) is a dietary strategy in which energy is consumed over a 6-10h window during the day and is associated with reduced energy intake and subsequent weight loss in people with obesity. However, the impact of isocaloric TRE on obesogenic factors such as hormones related to hunger and appetite, as well as energy expenditure and metabolic rate is relatively unknown. We therefore investigated the impact of 1 week of isocaloric TRE on obesity-related outcomes including circulating leptin, ghrelin, and peptide YY (PYY) and resting metabolic rate (RMR). Methods Thirteen healthy adults (8F, 26.9±3.9y, 23.3±2.1kg/m2) participated in a 2-week protocol. During Week 1, energy was consumed over a 13h period with meals individually anchored to habitual wake time and consumed at +1h, +6h, +11h and +14h after wake. For Week 2, participants were instructed to match energy intake from Week 1 but restrict intake to an 8h period (meals at +1h, +5h, and +9h after wake). At the end of each week, participants were admitted to the laboratory for an overnight stay. Blood samples were collected hourly overnight and assayed for leptin, ghrelin, and PYY. RMR was assessed using hood calorimetry immediately after wake. Results TRE was associated with a significant reduction in circulating leptin levels (p&amp;lt; 0.001) without changes in body weight (p=0.536), PYY or ghrelin levels. The respiratory exchange ratio (RER) calculated from hood calorimetry was significantly lower during TRE (0.76 vs 0.81; p=0.04) despite no change in energy expenditure (p=0.478) suggesting a higher reliance on fat oxidation during TRE compared with habitual eating. Conclusion Reductions in leptin in conjunction with lower RER suggests that TRE promotes increased fat utilization as compared with habitual eating. Future studies should evaluate whether long-term isocaloric TRE is associated with reduced adipose tissue mass. Support (if any) This project was supported by R01DK125653.

Fasting blood glucose, blood pressure and body mass index among combined oral contraceptive users in Chencha town Southern Ethiopia, 2019.

The use of contraceptives has become prevalent among women in Ethiopia. Oral contraceptive use has been suggested to trigger changes in glucose metabolism, energy expenditure, blood pressure, and body weight, among various populations and ethnic groups. To elucidate the pattern of fasting blood glucose, blood pressure, and body mass index among combined oral contraceptive pills users compared to controls. An institution-based cross-sectional study design was employed. A total of 110 healthy women using combined oral contraceptive pills were recruited as cases. Another 110 healthy age and sex-matched women not using any hormonal contraceptives were recruited as controls. A study was conducted between October 2018 and January 2019. Data obtained was entered and analyzed using IBM SPSS version 23 software packages. One-way ANOVA was used to identify the variation of variables in relation to the duration of use of the drug. The P-value of < 0.05 at the 95% confidence level was statistically significant. Fasting blood glucose level among oral contraceptive users (88.55 ± 7.89 mg/dl) was higher than fasting blood glucose level among oral contraceptive non-users (86.00 ± 9.85 mg/dl) with a p-value of 0.025. The mean arterial pressure of oral contraceptive users (88.2 ± 8.48 mmHg) was relatively higher than their counterparts (86.0 ± 6.74 mmHg), with a p-value of 0.04. Comparatively the body weight and body mass index among oral contraceptive users were 2.5% and 3.9% higher than non-users with a p-value of 0.03 and 0.003, respectively(5). Utilization of oral contraceptive pills for prolonged period of time seemed to be a significant predictive factor for higher mean arterial pressure and body mass index with p < 0.001and p < 0.05 respectively. Use of combined oral contraceptives was associated with higher fasting blood glucose (+2.9%), mean arterial pressure (+2.5%), and body mass index (3.9%) compared to controls.

Sensory detection of female olfactory cues as a central regulator of energy metabolism and body weight in male mice

Olfactory stimuli from food influence energy balance, preparing the body for digestion when food is consumed. Social chemosensory cues predict subsequent energetic changes required for social interactions and could be an additional sensory input influencing energy balance. We show that exposure to female chemostimuli increases metabolic rate in male mice and reduces body weight and adipose tissue expansion when mice are fed a high-fat diet. These responses are linked to detection of female chemostimuli via G-protein Gαo-expressing vomeronasal sensory neurons. Males with Gαo deleted in the olfactory system are fertile but do not show changes in body weight when paired with females and show severely blunted changes in energy expenditure when exposed to female bedding. These results establish that metabolic and reproductive responses to females can be partly uncoupled in male mice and that detection of female chemostimuli is a central regulator of energy metabolism and lipid storage.

Sequential changes in body composition and metabolic response after pancreatic trauma

ObjectivesPancreatic trauma and subsequent pancreatic operation result in early pathophysiologic alterations. Understanding changes in energy expenditure and body composition is essential for optimal management. This study aims to observe changes in energy expenditure and body composition in patients during the early postoperative days (PODs) after pancreatic trauma. MethodsThis is a retrospective review of patients who underwent surgery for blunt pancreatic trauma in a single trauma center. Data of body composition by bioimpedance spectroscopy and energy expenditure by indirect calorimetry were collected and analyzed in patients during the early PODs. The association of body composition parameters with major complications was analyzed. ResultsForty-one patients were included. Compared with POD-3, the total body water, extracellular water, fat-free mass, and skeletal muscle mass on POD-7 and -14 decreased significantly (all P < 0.05). The phase angle (PhA) increased significantly from POD-3 to -14 (P < 0.05). Resting energy expenditure was significantly higher than predicted and remained high throughout the study period. Over the 14-d study period, delivered energy was escalated to the level of resting energy expenditure. The PhA was significantly lower in patients with severe morbidity than in those without (3.6 [3.3–4.2] versus 4.5 [4.2–5.0]; P < 0.001). A multivariate analysis found that PhA was the independent variable for severe complications, with an odds ratio of 0.069 (95% CI, 0.011–0.427; P = 0.004). The predictive ability of PhA revealed an area under the receiver operating characteristic curve of 0.837, with an optimal threshold of 4.23. ConclusionsChanges in body composition and hypermetabolism state were observed from POD-3 to -14 after pancreatic trauma. A postoperative value of PhA < 4.23 is associated with severe complications.

Energy Balance, Hormonal Status, and Military Performance in Strenuous Winter Training

Severe energy deficit may impair hormonal regulation and physical performance in military trainings. The aim of this study was to examine the associations between energy intake, expenditure, and balance, hormones and military performance during a winter survival training. Two groups were studied: the FEX group (n = 46) had 8-day garrison and field training, whereas the RECO group (n = 26) had a 36-h recovery period after the 6-day garrison and field training phase. Energy intake was assessed by food diaries, expenditure via heart rate variability, body composition by bioimpedance, and hormones by blood samples. Strength, endurance and shooting tests were done for evaluating military performance. PRE 0 d, MID 6 d, POST 8 d measurements were carried out. Energy balance was negative in PRE and MID (FEX -1070 ± 866, -4323 ± 1515; RECO -1427 ± 1200, -4635 ± 1742 kcal·d-1). In POST, energy balance differed between the groups (FEX -4222 ± 1815; RECO -608 ± 1107 kcal·d-1 (p < 0.001)), as well as leptin, testosterone/cortisol ratio, and endurance performance (p = 0.003, p < 0.001, p = 0.003, respectively). Changes in energy intake and expenditure were partially associated with changes in leptin and the testosterone/cortisol ratio, but not with physical performance variables. The 36-h recovery restored energy balance and hormonal status after strenuous military training, but these outcomes were not associated with strength or shooting performance.

Durability is improved by both low and high intensity endurance training.

Introduction: This is one of the first intervention studies to examine how low- (LIT) and high-intensity endurance training (HIT) affect durability, defined as 'time of onset and magnitude of deterioration in physiological-profiling characteristics over time during prolonged exercise'. Methods: Sedentary and recreationally active men (n = 16) and women (n = 19) completed either LIT (average weekly training time 6.8 0.7h) or HIT (1.6 0.2h) cycling for 10 weeks. Durability was analyzed before and after the training period from three factors during 3-h cycling at 48% of pretraining maximal oxygen uptake (VO2max): 1) by the magnitude and 2) onset of drifts (i.e. gradual change in energy expenditure, heart rate, rate of perceived exertion, ventilation, left ventricular ejection time, and stroke volume), 3) by the 'physiological strain', defined to be the absolute responses of heart rate and its variability, lactate, and rate of perceived exertion. Results: When all three factors were averaged the durability was improved similarly (time x group p = 0.42) in both groups (LIT: p = 0.03, g = 0.49; HIT: p = 0.01, g = 0.62). In the LIT group, magnitude of average of drifts and their onset did not reach statistically significance level of p < 0.05 (magnitude: 7.7 6.8% vs. 6.3 6.0%, p = 0.09, g = 0.27; onset: 106 57min vs. 131 59 min, p = 0.08, g = 0.58), while averaged physiological strain improved (p = 0.01, g = 0.60). In HIT, both magnitude and onset decreased (magnitude: 8.8 7.9% vs. 5.4 6.7%, p = 0.03, g = 0.49; onset: 108 54min vs. 137 57 min, p = 0.03, g = 0.61), and physiological strain improved (p = 0.005, g = 0.78). VO2max increased only after HIT (time x group p < 0.001, g = 1.51). Conclusion: Durability improved similarly by both LIT and HIT based on reduced physiological drifts, their postponed onsets, and changes in physiological strain. Despite durability enhanced among untrained people, a 10-week intervention did not alter drifts and their onsets in a large amount, even though it attenuated physiological strain.

Active Glycogen Synthase in the Liver Prevents High-Fat Diet-Induced Glucose Intolerance, Decreases Food Intake, and Lowers Body Weight.

Many lines of evidence demonstrate a correlation between liver glycogen content and food intake. We previously demonstrated that mice overexpressing protein targeting to glycogen (PTG) specifically in the liver-which have increased glycogen content in this organ-are protected from high-fat diet (HFD)-induced obesity by reduced food intake. However, the use of PTG to increase liver glycogen implies certain limitations. PTG stimulates glycogen synthesis but also inhibits the enzyme responsible for glycogen degradation. Furthermore, as PTG is a regulatory subunit of protein phosphatase 1 (PP1), which regulates many cellular functions, its overexpression could have side effects beyond the regulation of glycogen metabolism. Therefore, it is necessary to determine whether the direct activation of glycogen synthesis, without affecting its degradation or other cellular functions, has the same effects. To this end, we generated mice overexpressing a non-inactivatable form of glycogen synthase (GS) specifically in the liver (9A-MGSAlb mice). Control and 9a-MGSAlb mice were fed a standard diet (SD) or HFD for 16 weeks. Glucose tolerance and feeding behavior were analyzed. 9A-MGSAlb mice showed an increase in hepatic glycogen in fed and fasting conditions. When fed an HFD, these animals preserved their hepatic energy state, had a reduced food intake, and presented a lower body weight and fat mass than control animals, without changes in energy expenditure. Furthermore, 9A-MGSAlb animals showed improved glucose tolerance when fed an SD or HFD. Moreover, liver triacylglycerol levels that were increased after HFD feeding were lower in these mice. These results confirm that increased liver glycogen stores contribute to decreased appetite and improve glucose tolerance in mice fed an HFD. On the basis of our findings, strategies to preserve hepatic glycogen stores emerge as potential treatments for obesity and hyperglycemia.

Understanding the role of growth hormone in situations of metabolic stress.

Growth hormone (GH) is secreted by the anterior pituitary gland and plays a key role in controlling tissue and body growth. While basal GH secretion is considerably reduced along adulthood and aging, several situations of metabolic stress can lead to robust increases in circulating GH levels. The objective of the present review is to summarize and discuss the importance of GH regulating different physiological functions in situations of metabolic stress, including prolonged food restriction, hypoglycemia, exercise, pregnancy, and obesity. The presented data indicate that GH increases hunger perception/food intake, fat mobilization, blood glucose levels and insulin resistance, as well as produces changes in energy expenditure and neuroendocrine responses during metabolic challenges. When all these effects are considered in the context of situations of metabolic stress, they contribute to restore homeostasis by 1) helping the organism to use appropriate energy substrates; 2) preventing hypoglycemia or increasing the availability of glucose; 3) stimulating feeding to provide nutrients in response to energy-demanding activities or to accelerate the recovery of energy stores; and 4) affecting the activity of neuronal populations involved in the control of metabolism and stress response. Thus, the central and peripheral effects of GH coordinate multiple adaptations during situations of metabolic stress that ultimately help the organism restore homeostasis, increasing the chances of survival.

Resting energy expenditure changes after antineoplastic treatment in gynecological cancer: a prospective pilot study

Resting energy expenditure changes after antineoplastic treatment in gynecological cancer: a prospective pilot study

Lysine or Threonine Deficiency Decreases Body Weight Gain in Growing Rats despite an Increase in Food Intake without Increasing Energy Expenditure in Response to FGF21

The objective of this study is to evaluate the effects of a strictly essential amino acid (lysine or threonine; EAA) deficiency on energy metabolism in growing rats. Rats were fed for three weeks severely (15% and 25% of recommendation), moderately (40% and 60%), and adequate (75% and 100%) lysine or threonine-deficient diets. Food intake and body weight were measured daily and indirect calorimetry was performed the week three. At the end of the experimentation, body composition, gene expression, and biochemical analysis were performed. Lysine and threonine deficiency induced a lower body weight gain and an increase in relative food intake. Lysine or threonine deficiency induced liver FGF21 synthesis and plasma release. However, no changes in energy expenditure were observed for lysine deficiency, unlike threonine deficiency, which leads to a decrease in total and resting energy expenditure. Interestingly, threonine severe deficiency, but not lysine deficiency, increase orexigenic and decreases anorexigenic hypothalamic neuropeptides expression, which could explain the higher food intake. Our results show that the deficiency in one EAA, induces a decrease in body weight gain, despite an increased relative food intake, without any increase in energy expenditure despite an induction of FGF21.

Effects of 8-Week Electromyostimulation Training on Upper-Limb Muscle Activity and Respiratory Gas Analysis in Athletes with Disabilities.

This study was aimed at verifying the efficacy of EMS training by investigating the changes in upper-limb muscle functions and energy expenditure in athletes with disabilities after an 8-week intervention of EMS training. We compared variations in muscle activity, respiratory gas, and symmetry index (SI) after an 8-week intervention in eight professional male athletes with disabilities wearing an electromyostimulation (EMS) suit (age: 42.00 ± 8.67 years, height: 1.65 ± 0.16 m, weight: 64.00 ± 8.72 kg, career length: 11.75 ± 3.83 years). For EMS training, each participant wore an EMS suit. EMS was applied to the upper-limb muscles pectoralis major and triceps at 40 °C water temperature, with a 25 Hz frequency (duty cycle 10%) for 15 min, followed by a 5 Hz frequency (duty cycle 5%) for 5 min. The pre- and post-intervention measurements were taken in the same way at a pre-set time (for 1 h, twice a week) for 8 weeks. Training involved a seated chest press, and the muscle activity (pectoralis major, triceps, and antebrachial muscles), upper-limb SI, and respiratory gas variables (maximal oxygen consumption (VO2), carbon dioxide output (VCO2), respiratory quotient (RQ), metabolic equivalents (METs), and energy expenditure per min (Energy expended per minute; EEm)) were analyzed. Variations pre- and post-intervention across the measured variables were analyzed. Regarding the change in muscle activity, significant variations were found in the pectoralis major right (p < 0.004), pectoralis major left (p < 0.001), triceps right (p < 0.002), and antebrachial right (p < 0.001). Regarding left-to-right SI, a positive change was detected in the pectoralis major and triceps muscles. Additionally, respiratory gas analysis indicated significant variations in VO2 (p < 0.001), VCO2 (p < 0.001), METs (p < 0.001), and EEm (p < 0.001). EMS training improved muscle strength and respiratory gas variables and is predicted to contribute to enhanced muscle function and rehabilitation training for athletes with disabilities.

Metabolic responses of predators to prey density

The metabolic cost of foraging is the dark energy of ecological systems. It is much harder to observe and to measure than its beneficial counterpart, prey consumption, yet it is not inconsequential for the dynamics of prey and predator populations. Here I define the metabolic response as the change in energy expenditure of predators in response to changes in prey density. It is analogous and intrinsically linked to the functional response, which is the change in consumption rate with prey density, as they are both shaped by adjustments in foraging activity. These adjustments are adaptive, ubiquitous in nature, and are implicitly assumed by models of predator–prey dynamics that impose consumption saturation in functional responses. By ignoring the associated metabolic responses, these models violate the principle of energy conservation and likely underestimate the strength of predator–prey interactions. Using analytical and numerical approaches, I show that missing this component of interaction has broad consequences for dynamical stability and for the robustness of ecosystems to persistent environmental or anthropogenic stressors. Negative metabolic responses – those resulting from decreases in foraging activity when more prey is available, and arguably the most common – lead to lower local stability of food webs and a faster pace of change in population sizes, including higher excitability, higher frequency of oscillations, and quicker return times to equilibrium when stable. They can also buffer the effects of press perturbations, such as harvesting, on target populations and on their prey through top-down trophic cascades, but are expected to magnify bottom-up cascades, including the effects of nutrient enrichment or the effects of altering lower trophic levels that can be caused by environmental forcing and climate change. These results have implications for any resource management approach that relies on models of food web dynamics, which is the case of many applications of ecosystem-based fisheries management. Finally, besides having their own individual effects, metabolic responses have the potential to greatly alter, or even invert, functional response-stability relationships, and therefore can be critical to an integral understanding of predation and its influence on population dynamics and persistence.

Effect of Inonotus obliquus Extract Supplementation on Endurance Exercise and Energy-Consuming Processes through Lipid Transport in Mice

Inonotus obliquus (IO) is used as functional food to treat diabetes. This study investigated the effect of IO supplementation on body composition in relation to changes in energy expenditure and exercise performance. Male Institute of Cancer Research mice were divided into four groups (n = 8 per group) and orally administered IO once daily for 6 wk at 0 (vehicle), 824 (IO-1×), 1648 (IO-2×), and 2472 mg/kg (IO-3×). IO supplementation increased muscle volume, exhaustive treadmill time, and glycogen storage in mice. Serum free fatty acid levels after acute exercise improved in the IO supplementation group, which exhibited changes in energy expenditure through the peroxisome proliferator-activated receptor (PPAR) pathway. RNA sequencing revealed significantly increased PPAR signaling; phenylalanine, ascorbate, aldarate, and cholesterol metabolism; chemical carcinogenesis; and ergosterol biosynthesis in the IO group compared with the vehicle group. Thus, IO supplements as nutraceuticals have a positive effect on lipid transport and exercise performance. In addition, this study was only IO supplementation without training-related procedures.

Hypothalamic TTF-1 orchestrates the sensitivity of leptin

ObjectiveThyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor, is predominantly expressed in discrete areas of the hypothalamus, which acts as the central unit for the regulation of whole-body energy homeostasis. Current study designed to identify the roles of TTF-1 on the responsiveness of the hypothalamic circuit activity to circulating leptin and the development of obesity linked to the insensitivity of leptin. MethodsWe generated conditional knock-out mice by crossing TTF-1flox/flox mice with leptin receptor (ObRb)Cre or proopiomelanocortin (POMC)Cre transgenic mice to interrogate the contributions of TTF-1 in leptin signaling and activity. Changes of food intake, body weight and energy expenditure were evaluated in standard or high fat diet-treated transgenic mice by using an indirect calorimetry instrument. Molecular mechanism was elucidated with immunohistochemistry, immunoblotting, quantitative PCR, and promoter assays. ResultsThe selective deletion of TTF-1 gene expression in cells expressing the ObRb or POMC enhanced the anorexigenic effects of leptin as well as the leptin-induced phosphorylation of STAT3. We further determined that TTF-1 inhibited the transcriptional activity of the ObRb gene. In line with these findings, the selective deletion of the TTF-1 gene in ObRb-positive cells led to protective effects against diet-induced obesity via the amelioration of leptin resistance. ConclusionsCollectively, these results suggest that hypothalamic TTF-1 participates in the development of obesity as a molecular component involved in the regulation of cellular leptin signaling and activity. Thus, TTF-1 may represent a therapeutic target for the treatment, prevention, and control of obesity.

How stable is your vivarium's temperature? Fluctuations in vivarium temperature significantly impact metabolism and behavior impeding scientific reproducibility

ObjectivesThe purpose of this investigation was to examine the variability in vivarium temperature and the impact that this has on metabolic and behavioral outcomes in mice. MethodsDaily vivarium temperature was monitored every day for a two-year period. Behavioral and metabolic phenotyping were assessed in male and female C57BL/6 (n = 71/sex) mice over the course of 2 years. ResultsVivarium temperature was found to fluctuate on a monthly, daily, and even an hourly basis of approximately ±5ºC. A 5ºC change in temperature was found to result in daily changes in total energy expenditure (35% and 27%), resting energy expenditure (39% for both sexes), movement (51% and 37%), food consumption (35% and 29%), and sleep duration (15% and 13%) for female and male mice, respectively. ConclusionsFluctuations in vivarium temperature can dramatically impact metabolic and behavioral outcomes, which impedes scientific reproducibility. This awareness and the guidelines we propose in this publication will hopefully help to enhance the reproducibility of pre-clinical animal research.

Gap junctions regulate the activity of AgRP neurons and diet-induced obesity in male mice.

Recent studies indicated an important role of connexins, gap junction proteins, in the regulation of metabolism. However, most of these studies focused on the glial expression of connexins, whereas the actions of connexins in neurons are still poorly investigated. Thus, the present study had the objective to investigate the possible involvement of gap junctions, and in particular connexin 43 (CX43), for the central regulation of energy homeostasis. Initially, we demonstrated that hypothalamic CX43 expression was suppressed in fasted mice. Using whole-cell patch-clamp recordings, we showed that pharmacological blockade of gap junctions induced hyperpolarization and decreased the frequency of action potentials in 50-70% of agouti-related protein (AgRP)-expressing neurons, depending on the blocker used (carbenoxolone disodium, TAT-Gap19 or Gap 26). When recordings were performed with a biocytin-filled pipette, this intercellular tracer was detected in surrounding cells. Then, an AgRP-specific CX43 knockout (AgRPΔCX43) mouse was generated. AgRPΔCX43 mice exhibited no differences in body weight, adiposity, food intake, energy expenditure and glucose homeostasis. Metabolic responses to 24 h fasting or during refeeding were also not altered in AgRPΔCX43 mice. However, AgRPΔCX43 male, but not female mice, exhibited a partial protection against high-fat diet-induced obesity, even though no significant changes in energy intake or expenditure were detected. In summary, our findings indicate that gap junctions regulate the activity of AgRP neurons, and AgRP-specific CX43 ablation is sufficient to mildly prevent diet-induced obesity specifically in males.