Metabolic Chamber Research Articles

Effects of 12 weeks of resistance exercise on 24-hour subjective appetite measured under highly controlled conditions inside a metabolic chamber in older men

Effects of 12 weeks of resistance exercise on 24-hour subjective appetite measured under highly controlled conditions inside a metabolic chamber in older men

Setting Treadmill Intensity for Rat Aerobic Training Using Lactate and Gas Exchange Thresholds.

To open up new horizons of translational research, we studied the lactate threshold (LT)-dependent physiological responses and adaptations to exercise in rats, highlighting the importance of intensity-specific studies for optimizing exercise prescriptions. LT is physiologically related to the non-invasive gas exchange threshold (GET), and both thresholds are moderate-heavy-intensity boundary indices in determining an effective intensity of aerobic training in humans. While their practical utility is presumed to extend to rats, the actual existence of GET, the thresholds' relations to maximal oxygen consumption (VO2max), and whether aerobic adaptations by training differ around the LT intensity remain uncertain. This study sought to identify the GET using our previously established rat LT-model by combining the use of a metabolic chamber and the V-slope method and to confirm the thresholds' relations to VO2max. We investigated changes in the thresholds and VO2max following 6 weeks of endurance training at below or above LT intensity. GET and LT were significantly correlated, and agreed with high precision, although with a fixed bias. Untrained rats exhibited GET and LT at 56% and 52% of their VO2max, respectively. Endurance training at supra-, but not below-, the LT intensity significantly improved VO2max and both thresholds; however, their %VO2max remained unaltered. GET in rats is identifiable as a threshold associated with LT using the V-slope method. Further, both thresholds can serve as moderate-heavy-intensity boundary indices for the aerobic training of rats. This study advances our understanding of exercise intensity regulation in rats, thereby contributing to the development of a more nuanced and effective model for exercise prescription, with implications for human health and fitness.

Chronic effects of a high protein diet on body mass, energy intake, and 24-hour subjective appetite measured under highly controlled conditions inside a metabolic chamber in older men

Chronic effects of a high protein diet on body mass, energy intake, and 24-hour subjective appetite measured under highly controlled conditions inside a metabolic chamber in older men

Effects of Diel Oxygen Cycling and Benthic Macrofauna on Sediment Oxygen Demand

This field study examined how sediment macroinfauna change patterns of sediment oxygen demand (SOD) throughout a diel oxygen cycle. Sediments with a greater faunal presence would be expected to have greater overall SOD, and at night may alter their behavior and influence SOD depending on their response to low-oxygen stress. Dynamic faunal bioturbation or bioirrigation behavior would also result in corresponding variation in SOD values on short time scales. In situ flow-through benthic metabolism chambers were used to measure SOD at a high temporal resolution in discrete sediment patches. Sediments with more macroinfauna had greater average SOD over the diel cycle, consistent with previous studies. Where more macroinfauna were present, they drove greater SOD during nightly low oxygen, presumably by enhancing their burrowing and irrigation activities. SOD was also more variable on a sub-diel timescale in sediments with more macroinfauna. Sediment oxygen demand is dynamic and highly sensitive both temporally, on very short timescales, and spatially, in terms of resident fauna, and their interaction produces heretofore unaccounted complexity in patterns of SOD particularly in shallow coastal systems. Extrapolations of temporally and spatially limited SOD measurements to a system-wide scale that do not account for the short-term and spatially variable effects of fauna may produce imprecise and misleading estimates of this critical ecosystem function.

Sex-specific role of high-fat diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus

BackgroundScientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice.MethodsTo investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis.ResultsWe observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress.ConclusionsOverall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health.

Alpha-melanocyte-stimulating hormone contributes to an anti-inflammatory response to lipopolysaccharide

ObjectiveDuring infection, metabolism and immunity react dynamically to promote survival through mechanisms that remain unclear. Pro-opiomelanocortin (POMC) cleavage products are produced and released in the brain and in the pituitary gland. One POMC cleavage product, alpha-melanocyte-stimulating hormone (α-MSH), is known to regulate food intake and energy expenditure and has anti-inflammatory effects. However, it is not known whether α-MSH is required to regulate physiological anti-inflammatory responses. We recently developed a novel mouse model with a targeted mutation in Pomc (Pomctm1/tm1 mice) to block production of all α-MSH forms which are required to regulate metabolism. To test whether endogenous α-MSH is required to regulate immune responses, we compared acute bacterial lipopolysaccharide (LPS)-induced inflammation between Pomctm1/tm1 and wild-type Pomcwt/wt mice. MethodsWe challenged 10- to 14-week-old male Pomctm1/tm1 and Pomcwt/wt mice with single i.p. injections of either saline or low-dose LPS (100 μg/kg) and monitored immune and metabolic responses. We used telemetry to measure core body temperature (Tb), ELISA to measure circulating cytokines, corticosterone and α-MSH, and metabolic chambers to measure body weight, food intake, activity, and respiration. We also developed a mass spectrometry method to measure three forms of α-MSH produced in the mouse hypothalamus and pituitary gland. ResultsLPS induced an exaggerated immune response in Pomctm1/tm1 compared to Pomcwt/wt mice. Both groups of mice were hypoactive and hypothermic following LPS administration, but Pomctm1/tm1 mice were significantly more hypothermic compared to control mice injected with LPS. Pomctm1/tm1 mice also had reduced oxygen consumption and impaired metabolic responses to LPS compared to controls. Pomctm1/tm1 mice had increased levels of key proinflammatory cytokines at 2 h and 4 h post LPS injection compared to Pomcwt/wt mice. Lastly, Pomcwt/wt mice injected with LPS compared to saline had increased total α-MSH in circulation 2 h post injection. ConclusionsOur data indicate endogenous α-MSH contributes to the inflammatory immune responses triggered by low-dose LPS administration and suggest that targeting the melanocortin system could be a potential therapeutic for the treatment of sepsis or inflammatory disease.

Time-dependent changes in feeding behavior and energy balance associated with weight gain in mice fed obesogenic diets.

Obesity is characterized by dysregulated homeostatic mechanisms resulting in positive energy balance; however, when this dysregulation occurs is unknown. We assessed the time course of alterations to behaviors promoting weight gain in male and female mice switched to an obesogenic high-fat diet (HFD). Male and female C57BL/6J mice were housed in metabolic chambers and were switched from chow to a 60% or 45% HFD for 4 and 3 weeks, respectively. Food intake, meal patterns, energy expenditure (EE), and body weight were continuously measured. A separate cohort of male mice was switched from chow to a 60% HFD and was given access to locked or unlocked running wheels. Switching mice to obesogenic diets promotes transient bouts of hyperphagia during the first 2 weeks followed by persistent caloric hyperphagia. EE increases but not sufficiently enough to offset increased caloric intake, resulting in a sustained net positive energy balance. Hyperphagia is associated with consumption of calorically larger meals (impaired satiation) more frequently (impaired satiety), particularly during the light cycle. Running wheel exercise delays weight gain in male mice fed a 60% HFD by enhancing satiation and increasing EE. However, exercise effects on satiation are no longer apparent after 2 weeks, coinciding with weight gain. Exposure to obesogenic diets engages homeostatic regulatory mechanisms for ~2 weeks that ultimately fail, and consequent weight gain is characterized by impaired satiation and satiety. Insights into the etiology of obesity can be obtained by investigating changes to satiation and satiety mechanisms during the initial ~2 weeks of HFD exposure.

Response to Hyperthermia and Hypoxia Stress during Compensatory Growth in Penaeus vannamei

This study evaluated oxidative stress and resistance to abiotic stress factors of juvenile Penaeus vannamei during compensatory growth. Shrimp underwent two dietary treatments in a 50-day experiment: a reference group (REF) fed ad libitum and a restricted group (T50) fed 50% of the REF diet for 10 days, followed by 40 days of ad libitum refeeding. During refeeding, shrimp from both groups were exposed to two abiotic challenges: 1) hyperthermia (34°C) for 12 hours and 2) hypoxia (1.5 mgO2 L-1) for 9 hours, followed by reoxygenation for 3 hours (5 mgO2 L-1). Compensatory growth in the T50 group was evidenced by increased specific growth rate, hyperphagia, and improved feed efficiency. Moreover, the malondialdehyde content (MDA) and catalase activity in the shrimp hepatopancreas increased during compensatory growth, indicating oxidative stress. This result converges with the increased metabolism assessed by metabolic chambers. While hyperthermia caused oxidative stress, as indicated by the increase in MDA content in both groups, shrimp under compensatory growth demonstrated similar resistance to the REF group. Exposition to hypoxia and reoxygenation did not generate significant oxidative stress. Compensatory growth induced oxidative stress in P. vannamei without compromising resistance to hyperthermia or hypoxia events.

Abstract 1785: The role of BRCA1 on metabolic pathways in an in vivo system

Abstract The role of BRCA1 in cellular metabolism is not well characterized and what we do understand has been mostly demonstrated in vitro. Our studies aim to fully characterize the role of BRCA1 in metabolic pathways in a whole-body system. In vivo studies using C57BL/6 wild-type and transgenic humanized BRCA1 mice demonstrate the effect of human BRCA1 on the whole-body metabolic phenotype and start to elucidate the mechanism by which this occurs. We used Promethion metabolic chambers and glucose tolerance tests to measure a number of metabolic outputs of male and female mice that had either normal mouse Brca1 gene expression (wild-type/WT mice) or a knock-out mouse Brca1/knock-in human BRCA1 (humanized/HU mice). Humanized BRCA1 mice are more lean, hyperactive and demonstrate a sexual dimorphism in glucose tolerance when compared to wild-type mice on the same genetic background. To begin to elucidate the mechanisms behind the observed metabolic phenotype, we used a metabolic tissue, female mouse skeletal muscle, to perform mass spectrometry, SuperArray, and Western blot analysis. Proteomic samples were sent to the IDeA National Resource for Quantitative Proteomics at the University of Arkansas Medical Sciences for processing and analysis. Proteomic and genomic analysis showed changes in a number of metabolic pathways that may be implicated in the observed whole body metabolic phenotype. We can conclude that changing the expression levels of BRCA1 in an in vivo model altered the overall metabolic profile of C57BL/6 mice. This is the first in vivo evidence demonstrating the effects of BRCA1 expression in whole body metabolism. Citation Format: Stacey L. Hembruff, Alexander Dekonenko, John Thyfault, Mihaela Sardiu, Michael Washburn, Roy A. Jensen, Lisa M. Harlan-Williams. The role of BRCA1 on metabolic pathways in an in vivo system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1785.

Differential effects of milk, yogurt, and cheese on energy homeostasis and brown adipose tissue phenotype in high-fat diet-induced obese mice.

Aim: We hypothesized that milk, yogurt, and cheese have differential impacts on energy expenditure (EE) and obesity in mice fed a high-fat diet (HFD). Methods: C57BL/6 mice (n = 16 per group) were fed a HFD or a HFD supplemented with fat-free milk (MILK), fat-free plain yogurt (YOG), or reduced-fat cheddar cheese (CHE; 19 kcal% fat), each provided at 10% of the daily energy intake, for 8 weeks. EE was quantified using a metabolic chamber. Metabolic pathways related to BAT mitochondrial function and uncoupling protein 1 (UCP1) abundance were assessed. Serum lipidomic profiles were analyzed to identify potential mediators of the observed effects. Results: MILK supplementation lowered weight gain and fat accumulation and enhanced EE and BAT thermogenesis, perhaps via the SIRT1-AMPK-PGC1α axis in BAT. This led to elevated UCP1 abundance and enhanced the abundance of hormone-sensitive lipase (HSL). MILK also altered serum lipid species, indicating enhanced energy use, and promoted BAT thermogenesis and mitochondrial function pathways. YOG exhibited a similar pattern but a lower magnitude of effects than MILK on reducing weight gain and fat mass, increasing EE, and BAT thermogenic proteins, including AMPK-PGC1α-UCP1. Both MILK and YOG showed a relative increase in serum PC 15:0_15:0 and LPC 15:0. In contrast, CHE reduced weight gain and increased EE without impacting BAT thermogenesis proteins or serum lipid species. Conclusion: Our study showed that MILK, YOG, and CHE reduced weight gain in mice on a HFD by increasing EE. MILK and YOG also up-regulated BAT thermogenesis, while both additionally altered lipids involved in fat metabolism and inflammation. CHE did not affect BAT thermogenesis and lipid species compared to HFD.

골관절염 유발이 흰쥐의 에너지소비량 및 에너지 기질 이용에 미치는 영향

The purpose of this study was to investigate the effect on energy expenditure and energy substrate utilization for 24 hours in an osteoarthritis model. In the MIA group, arthritis was induced for 2 weeks by injecting MIA into the joint cavity of the knee, followed by foot print evaluation. In addition, energy expenditure and energy substrate utilization were measured for 24 hours in metabolic chamber. As a result of this study, first, the osteoarthritis model showed lower footprint intensity than the control group due to pain and gait problems during foot evaluation (p<.001). Second, the osteoarthritis model showed lower oxygen uptake and energy expenditure than the control group (p<.01, p<.05). Third, the osteoarthritis model showed higher carbohydrate oxidation and lower fat oxidation compared to the control group (p<.05, p<.01). In conclusion, it was shown that osteoarthritis induction reduces overall activity and thus reduces total energy expenditure, and the energy substrate used at this time is mainly carbohydrate, which is thought to be the result of the cell's recovery and production mechanism.

Climate Spaces and Cliffs: A Novel Bovine Thermodynamic and Mass Balances Model.

The effects of climate change on animals are typically viewed in terms of survivability and wellbeing. In this study, we broaden that purview to include climate impacts on reproductive capability. There are not only climate spaces for daily function, but climate cliffs that represent reproductive failures in the face of climate warming. This alternative focus suggests that climate warming challenges may be more immediate and profound than initially imagined. This research describes a state-of-the-art mechanistic model, Dairy Niche Mapper (DNM), and independent validation tests. Where test data are absent, the calculated results are consistent with expected responses. Simulations of metabolic chamber conditions reveal the local steady-state impacts of climate and animal variables on milk production capacity, metabolic rate, food consumption and water needs. Simulations of a temperature humidity index (THI) show strengths and limitations of that approach. Broader time- and spatial-scale calculations applied in the western and eastern halves of the northern hemisphere identify current and future monthly latitudinal climate change impacts on milk production potential, feed and water needs in dairy cows of different sizes. Dairy Niche Mapper (DNM) was developed from a broadly tested mechanistic microclimate-animal model, Niche Mapper (NM). DNM provides an improved quantitative understanding of the complex nonlinear interactions of climate variation and dairy bovine properties' effects on current and future milk production, feed and water needs for grazing and confinement dairy operations. DNM outputs include feasible activity times, milk production and water and feed needs of different-sized Holstein cows on high-grain (confinement feeding) versus high-forage (grazing feeding) diets at three arbitrary north latitudes, 12°, 30° and 60°, for North and Central America and for Asia. These three latitudes encompass current northern hemisphere bovine production environments and possible future production locations. The greatest impacts of climate change will be in the low elevations in tropical and subtropical regions. Global regions above 30° and below 60° latitude with reliable rainfall will be least affected by current projected levels of climate change. This work provides the basis for computational animal design for guiding agricultural development via breeding programs, genetic engineering, management options including siting or the manipulation of other relevant environmental and animal variables.

Development and testing of a metabolic chamber for effluent collection during whole eye perfusions

Ocular hypertension is caused by dysregulated outflow resistance regulation by the conventional outflow (CO) pathway. The physiology of the CO pathway can be directly studied during ex vivo ocular perfusions. In addition to measuring outflow resistance generation by the CO tissues, perfusion media that is conditioned by CO pathway cells can be collected upon exiting the eye as effluent. Thus, contents of effluent include factors contributed by upstream cells that report on the (dys)functionality of the outflow tissues. Two methods have been used in the past to monitor effluent contents from perfused eyes, each with their limitations. To overcome these limitations, we designed and printed a metabolic chamber to accommodate eyes of different sizes during perfusions. To test this new chamber, human eyes were perfused for 4 h at constant flow rate of 2.5 μl/min, while pressure was continuously monitored and effluent was collected every hour. Facility was 0.28 ± 0.16 μl/min/mmHg for OD eyes and 0.33 ± 0.11 μl/min/mmHg for OS eyes (n = 3). Effluent samples were protein rich, with protein concentration ranging from 2700 to 10,000 μg/ml for all eyes and timepoints (N = 3). Effluent samples expressed proteins that were actively secreted by the TM and easily detectible including MYOC and MMP2. Taken together, our model provides a reliable method to collect effluent from ex vivo human eyes, while maintaining whole globe integrity.

Deep Learning Methods To Classify Posture, Movement, And Activity Intensity From Hip And Wrist-worn Accelerometers. A Direct Observation And Metabolic Chamber Validation Study.

Deep Learning Methods To Classify Posture, Movement, And Activity Intensity From Hip And Wrist-worn Accelerometers. A Direct Observation And Metabolic Chamber Validation Study.

Extracts of Dunkelfelder Grape Seeds and Peel Increase the Metabolic Rate and Reduce Fat Deposition in Mice Maintained on a High-Fat Diet.

Chronic high-fat diet intake may induce obesity and increase the risk of metabolic syndrome. The pomace of grape (Vitis vinifera L.) is rich in polyphenols, which are candidates for anti-obesity therapy. The present study aimed to investigate the effects of Dunkelfelder grape seed extract (GSE) and grape peel extract (GPE) on lipid and energy metabolism disorders in mice maintained on a high-fat diet (HFD). Male nine-week C57BL/6J mice were randomly assigned to one of four groups, namely, the normal chow diet (ND), HFD, HFD plus GSE (400 mg/kg BW) administered by oral gavage, or HFD plus GPE (400 mg/kg BW) administered by oral gavage. There were eight mice per group, and the experiment was 14 weeks in duration. The results showed that GSE and GPE treatments did not affect energy intake in mice on a high-fat diet, but body weight gain was 24.5% and 17.3% lower in the GSE- and GPE-treated mice than in the HFD group, respectively. They also decreased blood triglyceride (TG), total cholesterol (TC), and fasting blood glucose levels and increased high-density lipoprotein cholesterol (HDL-C). In addition, GSE and GPE reduced adipose tissue weight and excessive lipid droplet accumulation in the adipocytes. The metabolic chamber test showed that the GSE and GPE treatments enhanced oxygen consumption, carbon dioxide production, and heat release while decreasing the respiratory exchange rate (RER). This suggests that GSE and GPE augmented fuel oxidation and energy generation and increased the proportion of lipids being utilized in energy metabolism. GSE and GPE also upregulated the genes controlling lipolysis and downregulated those controlling lipogenesis in adipose tissues. Moreover, they significantly increased the expression levels of the genes regulating thermogenesis in BAT, eWAT, and iWAT, and mitochondrial biogenesis in all three types of adipose tissue. In conclusion, the present study empirically demonstrated that GSE and GPE enhance body fat utilization by augmenting lipid and energy metabolism and could, therefore, ameliorate high-fat diet-induced obesity.

Squamate metabolic rates decrease in winter beyond the effect of temperature.

The reptilian form of hibernation (brumation) is much less studied than its mammalian and insect equivalents. Hibernation and brumation share some basic features but may differ in others. Evidence for hypometabolism in brumating reptiles beyond the effect of temperature is sporadic and often ignored. We calculated the standard metabolic rates (SMR, oxygen uptake during inactivity), in winter and/or summer, of 156 individuals representing 59 species of Israeli squamates across all 17 local families. For 32 species, we measured the same individuals during both seasons. We measured gas exchange continuously in a dark metabolic chamber, under the average January high and low temperatures (20°C and 12°C), during daytime and nighttime. We examined how SMR changes with season, biome, body size, temperature and time of day, using phylogenetic mixed models. Metabolic rates increased at sunrise in the diurnal species, despite no light or other external cues, while in nocturnal species the metabolic rates did not increase. Cathemeral species shifted from a diurnal-like diel pattern in winter to a nocturnal-like pattern in summer. Regardless of season, Mediterranean species SMRs were 30% higher than similar-sized desert species. Summer SMR of all species together scaled with body size with an exponent of 0.84 but dropped to 0.71 during brumation. Individuals measured during both seasons decreased their SMR between summer and winter by a 47%, on average, at 20°C and by 70% at 12°C. Q10 was 1.75 times higher in winter than in summer, possibly indicating an active suppression of metabolic processes under cold temperatures. Our results challenge the commonly held perception that squamate physiology is mainly shaped by temperature, with little role for intrinsic metabolic regulation. The patterns we describe indicate that seasonal, diel and geographic factors can trigger remarkable shifts in metabolism across squamate species.

Dietary palmitic acid to oleic acid ratio modulates energy metabolism and biological rhythms in young healthy Japanese males.

The present study investigated the potential role of the composition of dietary fatty acids in the regulation of biological rhythms, such as the sleep architecture, core body temperature and leukocyte clock gene expression, in subjects fed meals rich in palmitic acid (PA) or oleic acid (OA). Eleven males participated in two sessions of indirect calorimetry in a whole-room metabolic chamber. In each session, subjects consumed three meals rich in PA (44·3 % of total fat as PA and 42·3 % as OA) or OA (11·7 % of total fat as PA and 59·3 % as OA) in the metabolic chamber. The ratio of PA to OA in plasma was significantly lower and fat oxidation was significantly higher during 24 h of indirect calorimetry in the session with meals rich in OA than in that with meals rich in PA. The duration of slow wave sleep (SWS) was shorter, the latency of SWS was longer and the nadir of core body temperature after bedtime was later in the session with meals rich in PA than in that with meals rich in OA. The peak in CRY1 gene expression was earlier and its amplitude was higher in the session with meals rich in PA than in that with meals rich in OA. In healthy young males, meals rich in PA decreased fat oxidation and disrupted biological rhythms, particularly the sleep architecture and core body temperature during sleep, more than meals rich in OA.

An evaluation of a biophysical model for predicting avian thermoregulation in the heat.

Survival and reproduction of endotherms depend on their ability to balance energy and water exchange with their environment, avoiding lethal deficits and maximising gains for growth and reproduction. At high environmental temperatures, diurnal endotherms maintain body temperature (Tb) below lethal limits via physiological and behavioural adjustments. Accurate models of these processes are crucial for predicting effects of climate variability on avifauna. We evaluated the performance of a biophysical model (NicheMapR) for predicting evaporative water loss (EWL), resting metabolic rate (RMR) and Tb at environmental temperatures approaching or exceeding normothermic Tb for three arid-zone birds: southern yellow-billed hornbill (Tockus leucomelas), southern pied babbler (Turdoides bicolor) and southern fiscal (Lanius collaris). We simulated metabolic chamber conditions and compared model outputs with thermal physiology data collected at air temperatures (Tair) between 10 and 50°C. Additionally, we determined the minimum data needed to accurately model diurnal birds' thermoregulatory responses to Tair using sensitivity analyses. Predicted EWL, metabolic rate and Tb corresponded tightly with observed values across Tair, with only minor discrepancies for EWL in two species at Tair≈35°C. Importantly, the model captured responses at Tair=30-40°C, a range spanning threshold values for sublethal fitness costs associated with sustained hot weather in arid-zone birds. Our findings confirm how taxon-specific parameters together with biologically relevant morphological data can accurately model avian thermoregulatory responses to heat. Biophysical models can be used as a non-invasive way to predict species' sensitivity to climate, accounting for organismal (e.g. physiology) and environmental factors (e.g. microclimates).

Energy metabolism and thermoregulation during sleep in young and old females

Core body temperature (CBT) shows a diurnal rhythm, and the nocturnal decrease in CBT is blunted in older people. The physiological mechanisms responsible for the blunted nocturnal decrease in CBT in older people remain to be revealed. The aim of this study was to compare heat production and heat dissipation in young and old subjects during sleep, as assessed by indirect calorimetry and the distal–proximal temperature gradient (DPG) of skin temperature. A complete dataset of 9 young (23.3 ± 1.1 years) and 8 old (72.1 ± 2.5 years) females was analyzed. CBT and energy metabolism were monitored during sleep using an ingestible temperature sensor in a metabolic chamber maintained at 25 °C. Skin temperature was measured at proximal and distal parts of the body. CBT, distal skin temperature, and DPG in older subjects were higher than in young subjects. Protein oxidation was similar between the two groups, but fat oxidation was lower and carbohydrate oxidation was higher in old subjects compared to young subjects. On the other hand, energy expenditure was similar between the two age groups. Thus, the elevated CBT in older subjects was not attributed to deteriorated heat dissipation or enhanced heat production, suggesting an alternative explanation such as deteriorated evaporative heat loss in old subjects.

210-OR: Long-Acting GIPR Agonism Enhances Body Weight Regulation of Multiple Weight-Reducing Agents in Diet-Induced Obese Mice

The development of multi-agonists targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) has resulted in significant clinical improvements in body weight management, however the contribution of GIPR agonism to this effect is incompletely understood. Using a diet induced obese (DIO) mouse model, GIPR agonism (LAGIPRA) alone has demonstrated little to no efficacy in weight management, whereas the addition of LAGIPRA to long acting GLP-1R agonism decreased food intake and increased energy expenditure resulting in greater weight loss compared with GLP-1R agonism alone suggesting a synergistic benefit. To determine whether GIPR agonism would provide similar synergistic improvements in energy metabolism with additional pharmacologic drivers of weight loss, we treated DIO mice with various weight reducing agents plus and minus LAGIPRA in metabolic chambers. Interestingly, addition of LAGIPRA enhanced weight loss, fat mass reduction, energy expenditure, and lipid oxidation whether combined with T3, FGF21, or long-acting glucagon (IUB288); consistent with earlier experiments, it had little effect on its own. Assessment of adipose tissue engagement in these and subsequent studies suggest GIPR agonism in this tissue may enhance lipolysis, potentially enabling greater energy expenditure via release of stored lipids. These findings suggest a unique role for GIPR agonism to regulate energy expenditure when combined with molecules that reduce body weight generating a greater negative caloric balance and enhancing body weight reduction. Disclosure W.Roell: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.O'farrell: None. A.Regmi: Employee; Eli Lilly and Company. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.