Changes In Energy Expenditure Research Articles

Energy Expenditure in Humans: Principles, Methods, and Changes Throughout the Life Course.

Humans require energy to sustain their daily activities throughout their lives. This narrative review aims to (a) summarize principles and methods for studying human energy expenditure, (b) discuss the main determinants of energy expenditure, and (c) discuss the changes in energy expenditure throughout the human life course. Total daily energy expenditure is mainly composed of resting energy expenditure, physical activity energy expenditure, and the thermic effect of food. Total daily energy expenditure and its components are estimated using variations of the indirect calorimetry method. The relative contributions of organs and tissues determine the energy expenditure under different physiological conditions. Evidence shows that energy expenditure varies along the human life course, at least in part due to changes in body composition, the mass and specific metabolic rate of organs and tissues, and levels of physical activity. This information is crucial to estimate human energy requirements for maintaining health throughout the life course.

Cold exposure increases circulating fibroblast growth factor 21 in the evening in males and females.

Cold exposure is linked to cardiometabolic benefits. Cold activates brown adipose tissue (BAT), increases energy expenditure, and induces secretion of the hormones fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). The cold-induced increase in energy expenditure exhibits a diurnal rhythm in men. Therefore, we aimed to investigate the effect of cold exposure on serum FGF21 and GDF15 levels in humans and whether cold-induced changes in FGF21 and GDF15 levels differ between morning and evening in males and females. In this randomized cross-over study, serum FGF21 and GDF15 levels were measured in healthy lean males (n = 12) and females (n = 12) before, during, and after 90 min of stable cold exposure in the morning (07:45 h) and evening (19:45 h) with a 1-day washout period in between. Cold exposure increased FGF21 levels in the evening compared to the morning both in males (+61% vs -13%; P < 0.001) and in females (+58% vs +8%; P < 0.001). In contrast, cold exposure did not significantly modify serum GDF15 levels, and no diurnal variation was found. Changes in FGF21 and GDF15 levels did not correlate with changes in cold-induced energy expenditure in the morning and evening. Cold exposure increased serum FGF21 levels in the evening, but not in the morning, in both males and females. GDF15 levels were not affected by cold exposure. Thus, this study suggests that the timing of cold exposure may influence cold-induced changes in FGF21 levels but not GDF15 levels and seems to be independent of changes in energy expenditure.

Impact of lumacaftor/ivacaftor on nutrition and growth in modulator-naïve children over 24 weeks

BackgroundCystic fibrosis transmembrane conductance regulator (CFTR) modulators improve nutritional status and are of importance in achieving normal growth among younger children with CF. The study was designed to examine CFTR modulator-associated changes in nutrition status, including bile acids and fatty acids after lumacaftor/ivacaftor therapy for 24 weeks. MethodsChildren 2 to 5.9 years were recruited from US and Canadian CF Centers. Eligible children were lumacaftor/ivacaftor naïve and approved to initiate therapy. Anthropometrics, diet, energy expenditure, nutrition biomarkers, pancreatic status, serum and fecal calprotectin, serum bile acids and plasma fatty acids were measured. Changes from baseline at 12 and 24 weeks were examined using mixed effects linear regression modeling. ResultsWeight-for-age z-score (WAZ) increased at 12 (0.15 ± 0.1, p = 0.01) and 24 weeks (0.23 ± 0.1, p = 0.001) from baseline following modulator therapy. Head circumference-for-age (HCZ) increased at 12 weeks compared to baseline (0.22 ± 0.1, p = 0.03) and subscapular Z score increased from baseline at 24 weeks following therapy (0.33 ± 0.1, p = 0.02). There were no changes in energy expenditure. Serum total bile acids (6.7 ± 2.0, p = 0.001), chenodeoxycholic acid (CDCA) (2.4 ± 1.1, p = 0.001), and cholic acid (CA) (3.5 ± 0.8, p < 0.0001) increased at 24 weeks compared to baseline. Fecal calprotectin decreased at 12 and 24 weeks compared to baseline (-463 ± 310, p = 0.03 and 566 ± 347, p = 0.047). A number of plasma fatty acids changed over the course of 24 weeks of therapy. Noteably, alpha-linolenic acid (ALA) decreased at 12 and 24 weeks (-24 ± 10,p = 0.03 and -18 ± 10, p = 0.02, respectively). ConclusionsOverall, young children experienced favorable changes in nutritional and growth, with the exception of plasma ALA status in the first 24 weeks of lumacaftor/ivacaftor therapy.

Longitudinal change of energy expenditure, body composition and dietary habits in Progressive Supranuclear Palsy patients.

Alterations in metabolic status, body composition, and food intake are present in all neurodegenerative diseases. Aim of this study was to detect the progression of these changes in Progressive Supranuclear Palsy (PSP). We conducted a longitudinal study of 15 patients with PSP. The assessments were performed at baseline (T0) and after 7(IQR = 5) months of follow-up (T1). We collected anthropometric measures including body weight, height, body mass index and waist circumference, metabolic parameters through indirect calorimeters, body composition using bioimpedance analysis, and dietary habits with a validated questionnaire. PSP-rating scale (PSP-rs) was used to evaluate disease severity and dysphagia. The majority of patients (66.66%) presented PSP-Richardson Syndrome and 33.33% the other variant syndromes of the disease. At T1 there was a decrease in intake of total daily calories (p < 0.001), proteins (p < 0.001), fibers (p = 0.001), calcium (p = 0.008), iron (p < 0.001), zinc (0.034), vitamin E (p = 0.006) and folates (p = 0.038) compared to T0. No other changes were found. As for T1 data, no significant differences were shown according to disease phenotypes or the presence of clinically significant dysphagia for solids. Within a mid-term follow up, PSP patients presented reduced caloric and proteins intake regardless the presence of dysphagia. The PSP-rs is likely not adequate to assess dysphagia, which should be investigated by specific clinical scales or instrumental examinations. With the goal of maintaining adequate nutritional status, the administration of protein and vitamin supplements should be considered even in the absence of dysphagia evidenced by the rating scales.

Dual glucagon-like peptide-1 and glucagon receptor agonism reduces energy intake in type 2 diabetes with obesity.

To establish which components of energy balance mediate the clinically significant weight loss demonstrated with use of cotadutide, a glucagon-like peptide-1 (GLP-1)/glucagon receptor dual agonist, in early-phase studies. We conducted a phase 2a, single-centre, randomized, placebo-controlled trial in overweight and obese adults with type 2 diabetes. Following a 16-day single-blind placebo run-in, participants were randomized 2:1 to double-blind 42-day subcutaneous treatment with cotadutide (100-300 μg daily) or placebo. The primary outcome was percentage weight change. Secondary outcomes included change in energy intake (EI) and energy expenditure (EE). A total of 12 participants (63%) in the cotadutide group and seven (78%) in the placebo group completed the study. The mean (90% confidence interval [CI]) weight change was -4.0% (-4.9%, -3.1%) and -1.4% (-2.7%, -0.1%) for the cotadutide and placebo groups, respectively (p = 0.011). EI was lower with cotadutide versus placebo (-41.3% [-66.7, -15.9]; p = 0.011). Difference in EE (per kJ/kg lean body mass) for cotadutide versus placebo was 1.0% (90% CI -8.4, 10.4; p = 0.784), assessed by doubly labelled water, and -6.5% (90% CI -9.3, -3.7; p < 0.001), assessed by indirect calorimetry. Weight loss with cotadutide is primarily driven by reduced EI, with relatively small compensatory changes in EE.

Hematological parameters vary with life history stage in the pale‐breasted thrush Turdus leucomelas

The avian life cycle is composed by a progressive sequence of life history stages (LHS). Changes in energy expenditure and exposure to stressors at different LHS require corresponding changes in behavior, physiology, and morphology. Variation in hematological parameters, such hematocrit (Hct), hemoglobin (Hb), and heterophil to lymphocyte ratio (H/L ratio), can have permissive, stimulatory, and preparative actions to help maintain homeostasis through different LHS. Few studies have examined differences in these parameters among different LHS in free‐living birds, with most of them restricted to temperate zones. We collected blood samples and measured hematological parameters every week for over a year from a population of a common resident bird species in southeastern Brazil, the pale‐breasted thrush Turdus leucomelas. Hematocrit and hemoglobin concentration were highest during the onset of the reproduction and lowest during molt. Furthermore, H/L ratios were higher at the end of the reproduction, indicating that the breeding season could be the most stressful period of the year for this population of thrushes. There was no difference between sexes for any hematological parameter at any LHS. These results show that there is a permissive physiological effect for Hct and Hb to facilitate LHS transitions and that reproduction could be the most stressful event for this species. Lastly, these results mirror those from temperate species despite distinct environmental differences between these regions.

Triptolide Administration Alters Immune Responses to Mitigate Insulin Resistance in Obese States.

Individuals who are overweight or obese are at increased risk of developing prediabetes and type 2 diabetes, yet the direct molecular mechanisms that connect diabetes to obesity are not clear. Chronic, sustained inflammation is considered a strong risk factor in these interactions, directed in part by the short-lived gene expression programs encoding for cytokines and pro-inflammatory mediators. In this study, we show that triptolide administration in the C57BL/6 diet-induced obese mice at up to 10 μg/kg/day for 10 weeks attenuated the development of insulin resistance and diabetes, but not obesity, in these animals. Significant reductions in adipose tissue inflammation and improved insulin sensitivity were observed in the absence of changes in food intake, body weight, body composition, or energy expenditure. Analysis of the core cluster of biomarkers that drives pro-inflammatory responses in the metabolic tissues suggested TNF-α as a critical point that affected the co-development of inflammation and insulin resistance, but also pointed to the putatively protective roles of increased COX-2 and IL-17A signaling in the mediation of these pathophysiological states. Our results show that reduction of diet-induced inflammation confers partial protection against insulin resistance, but not obesity, and suggest the possibility of achieving overweight phenotypes that are accompanied by minimal insulin resistance if inflammation is controlled.

Accelerated onset of diabetes in non-obese diabetic mice fed a refined high-fat diet.

Type 1 diabetes results from autoimmune events influenced by environmental variables, including changes in diet. This study investigated how feeding refined versus unrefined (aka 'chow') diets affects the onset and progression of hyperglycaemia in non-obese diabetic (NOD) mice. Female NOD mice were fed either unrefined diets or matched refined low- and high-fat diets. The onset of hyperglycaemia, glucose tolerance, food intake, energy expenditure, circulating insulin, liver gene expression and microbiome changes were measured for each dietary group. NOD mice consuming unrefined (chow) diets developed hyperglycaemia at similar frequencies. By contrast, mice consuming the defined high-fat diet had an accelerated onset of hyperglycaemia compared to the matched low-fat diet. There was no change in food intake, energy expenditure, or physical activity within each respective dietary group. Microbiome changes were driven by diet type, with chow diets clustering similarly, while refined low- and high-fat bacterial diversity also grouped closely. In the defined dietary cohort, liver gene expression changes in high-fat-fed mice were consistent with a greater frequency of hyperglycaemia and impaired glucose tolerance. Glucose intolerance is associated with an enhanced frequency of hyperglycaemia in female NOD mice fed a defined high-fat diet. Using an appropriate matched control diet is an essential experimental variable when studying changes in microbiome composition and diet as a modifier of disease risk.

Energy expenditure in healthy pregnant women: a systematic review.

Since pregnancy is a decisive period for women and children in terms of future health, it is very important to determine changes in energy expenditure and requirements. However, there is no reference method to determine the energy expenditure as there are many factors that change maternal energy homeostasis during this period. This review aims to evaluate the changes in energy expenditure during pregnancy and the effects of these changes on maternal weight gain, as well as the methods used to determine energy expenditure. Google Scholar, PubMed, ScienceDirect, Cochrane Library, and Wiley Online Library databases were searched to determine studies on energy expenditure during pregnancy between 2010 and 2022. Of the 2095 articles initially identified, 20 met the inclusion criteria for this review. Two independent reviewers selected and extracted data from those articles. The articles reviewed show that prepregnancy body mass index, gestational weight gain, changes in fat mass, and lean body mass influence energy expenditure during pregnancy. Doubly-labeled water and indirect calorimetric methods are considered reference methods for determining energy expenditure in pregnancy. Indirect calorimetric methods, when used together with body weight and physical activity measurements, allow an accurate estimation of resting energy expenditure and energy requirements for pregnant women. Metabolic Holter or accelerometers are valid methods for determining activity energy expenditure in pregnant women and are suitable for use during activity. Resting energy expenditure and activity energy expenditure should be carefully monitored and measured by valid methods to achieve the correct energy intake targets during pregnancy. The existing equations used in determining energy expenditure should be developed for a more accurate estimation of energy expenditure during pregnancy, or new pregnancy-specific equations should be derived.

Cumulative effect of obesity phenotypes on body weight and body mass index.

Obesity originates from an imbalance between energy intake and expenditure. Changes in energy intake components (satiation, postprandial satiety, emotional eating) and energy expenditure have been linked to obesity and are referred to as obesity phenotypes. We aim to study if these obesity phenotypes have a cumulative effect on body weight and body mass index (BMI). This is a cross-sectional study of adult patients with obesity (BMI > 30 kg/m2) who completed the validated tests to measure the obesity phenotypes. A total of 464 were included in this study. We defined higher calories to fullness during an ad libitum meal as abnormal satiation, accelerated time to half gastric emptying with scintigraphy as abnormal postprandial satiety, higher anxiety score on the Hospital Anxiety and Depression Scale as hedonic eating behavior, and decreased percentage of measured resting energy expenditure as abnormal energy expenditure. The primary analysis was done on the number of phenotypes ( ≤ 1 and ≥ 2) with body weight and BMI using an independent t-test. Our cohort included 464 patients (mean [SD] age 42.0 [10.9] years, 79% females, weight 111.2 [22.9] kg, BMI 38.9 [7.0] kg/m2). There were 294 patients who had ≤ 1 phenotype, and 170 patients with ≥ 2 phenotypes with no baseline demographical differences (i.e., age and sex). Having ≥ 2 phenotypes was associated with higher body weight (115 [25] kg vs. 109 [21] kg; p = 0.004), BMI (40 [8] kg/m2 vs. 38 [7] kg/m2; p = 0.02) and waist (118 [15] cm vs. 115 [13] cm; p = 0.04) and hip (129 [14] cm vs. 125 [13] cm; p = 0.01) circumferences compared to ≤ 1 phenotype. Obesity phenotypes are associated with an additive effect on the body weight and BMI. Patients who have multiple obesity phenotypes may require a more aggressive approach to enhance weight loss.

Insulin at the intersection of thermoregulation and glucose homeostasis

Mammals are protected from changes in environmental temperature by altering energetic processes that modify heat production. Insulin is the dominant stimulus of glucose uptake and metabolism, which are fundamental for thermogenic processes. The purpose of this work was to determine the interaction of ambient temperature induced changes in energy expenditure (EE) on the insulin sensitivity of glucose fluxes. Short-term and adaptive responses to thermoneutral temperature (TN, ∼28 °C) and room (laboratory) temperature (RT, ∼22 °C) were studied in mice. This range of temperature does not cause detectable changes in circulating catecholamines or shivering and postabsorptive glucose homeostasis is maintained. We tested the hypothesis that a decrease in EE that occurs with TN causes insulin resistance and that this reduction in insulin action and EE is reversed upon short term (<12h) transition to RT. Insulin-stimulated glucose disposal (Rd) and tissue-specific glucose metabolic index were assessed combining isotopic tracers with hyperinsulinemic-euglycemic clamps. EE and insulin-stimulated Rd are both decreased (∼50%) in TN-adapted vs RT-adapted mice. When RT-adapted mice are switched to TN, EE rapidly decreases and Rd is reduced by ∼50%. TN-adapted mice switched to RT exhibit a rapid increase in EE, but whole-body insulin-stimulated Rd remains at the low rates of TN-adapted mice. In contrast, whole body glycolytic flux rose with EE. This higher EE occurs without increasing glucose uptake from the blood, but rather by diverting glucose from glucose storage to glycolysis. In addition to adaptations in insulin action, ‘insulin-independent’ glucose uptake in brown fat is exquisitely sensitive to thermoregulation. These results show that insulin action adjusts to non-stressful changes in ambient temperature to contribute to the support of body temperature homeostasis without compromising glucose homeostasis.

Changes in blood oxygen transport function and body energy expenditure during anaesthesia during coronary artery bypass grafting in adults: A randomized clinical study

&lt;b&gt;Introduction:&lt;/b&gt; Cardiac surgery is a dangerous and complex field of medicine with significant morbidity and mortality. Quality anesthetic care with specific attention to detail can greatly enhance patient safety and outcome.&lt;br /&gt; &lt;b&gt;Objectives: &lt;/b&gt;Comparison of the effects of anesthetics on oxygen consumption, transport and energy expenditure during coronary artery bypass grafting in adults.&lt;br /&gt; &lt;b&gt;Material and methods: &lt;/b&gt;A total of 90 patients were assigned randomly into three groups according to the type of anaesthesia: the first group with propofol (P), the second group with sevoflurane, and the last one was with isoflurane. All patients underwent coronary artery bypass grafting under cardiopulmonary bypass. To determine oxygen delivery and oxygen consumption were determined using the formulas ((DO&lt;sub&gt;2&lt;/sub&gt; = CI* CaO&lt;sub&gt;2&lt;/sub&gt;), (VO&lt;sub&gt;2&lt;/sub&gt; = Cardiac index (CI)) and a spirometric device during anaesthesia.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;the cardiac index remained at the same level in the propofol and sevoflurane groups (2.5±0.6 l/min/m2 and 2.3±0.5 l/min/m2), while in the isoflurane group it was decreased to 2.3±0.5 l/min/m2. The oxygen transport index was 421.6±57.0 ml/min/m2 in the propofol group, 396.4±63.2 ml/min/m2 in the sevoflurane group, and 376.7±68.0 ml/min/m2 in the isoflurane group. Propofol reduced oxygen consumption to 101.5±23.5 ml/min/m2, while sevoflurane and isoflurane anesthesia reduced it to 106.6±22.3 ml/min/m2 and 116.4±21.4 ml/min/ m2. All anaesthetics reduced energy expenditure, but propofol anaesthesia significantly reduced it from 1491.4 to 1188.3 kcal/day.&lt;br /&gt; &lt;b&gt;Conclusion: &lt;/b&gt;In conclusion, isoflurane significantly reduced cardiac index compared to propofol and sevoflurane. Oxygen transport was higher in the propofol group than volatile anesthetics, and propofol reduced oxygen consumption more than inhalational anesthetics. In addition, energy expenditure was lowest in the propofol group than in the other anesthetics.

Changes in Energy Expenditure, Dietary Intake, and Energy Availability Across an Entire Collegiate Women's Basketball Season: Erratum.

Changes in Energy Expenditure, Dietary Intake, and Energy Availability Across an Entire Collegiate Women's Basketball Season: Erratum.

The effects of chemotherapy on resting energy expenditure, body composition, and cancer-related fatigue in women with breast cancer: a prospective cohort study

BackgroundBreast cancer (BC) is the most prevalent tumor in women. Improvements in treatment led to declined mortality, resulting in more survivors living with cancer- or therapy-induced comorbidities. In this study, we investigated the impact of neoplasia and chemotherapy on resting energy expenditure (REE) and body composition, in relation to cancer-related fatigue. Inflammatory parameters were checked as possible explanation for changes in REE.MethodsFifty-six women participated: 20 women with BC and 36 healthy controls. Patients were assessed at baseline (T0) and follow-up (T1) after 12 weeks of chemotherapy. Controls were measured once. REE was assessed with indirect calorimetry: body composition (body weight, fat mass, fat-free mass) by air plethysmography. The multidimensional fatigue index (MFI-20) was used to analyze fatigue. Baseline measurements of patients were compared to results of the healthy controls with the independent-samples T-test. The paired-samples T-test investigated the effects of chemotherapy from T0 to T1. A Pearson correlation analysis was conducted between REE, body composition, and fatigue and between REE, body composition, and inflammatory parameters. A linear regression analysis was fitted to estimate the contribution of the significantly correlated parameters. The measured REE at T0 and T1 was compared to the predicted REE to analyze the clinical use of the latter.ResultsAt baseline, patients with BC had significantly higher REE in the absence of differences in body composition. From baseline to T1, REE and body weight did not change. In contrast, fat-free mass declined significantly with concordant increase in fat mass. Fatigue deteriorated significantly. C-reactive protein at baseline predicted the change in energy expenditure. Predicted REE significantly underestimated measured REE.ConclusionsWomen with BC have higher REE in the tumor-bearing state compared to healthy controls. Chemotherapy does not affect REE but alters body composition. Predictive equations are invalid in the BC population. Results of our study can be used to implement personalized nutritional interventions to support energy expenditure and body composition and minimize long-term comorbidities.

Early-life sodium deprivation programs long-term changes in ingestive behaviors and energy expenditure in C57BL/6J mice.

Postnatal growth failure remains a significant problem for infants born prematurely, despite aggressive efforts to improve perinatal nutrition. Though often dysregulated in early life when children are born preterm, sodium (Na) homeostasis is vital to achieve optimal growth. We hypothesize that insufficient Na supply in this critical period contributes to growth restriction and programmed risks for cardiometabolic disease in later adulthood. Thus, we sought to ascertain the effects of prolonged versus early-life Na depletion on weight gain, body composition, food and water intake behaviors, and energy expenditure in C57BL/6J mice. In one study, mice were provided a low (0.04%)- or normal/high (0.30%)-Na diet between 3 and 18 wk of age. Na-restricted mice demonstrated delayed growth and elevated basal metabolic rate. In a second study, mice were provided 0.04% or 0.30% Na diet between 3 and 6 wk of age and then returned to standard (0.15%)-Na diet through the end of the study. Na-restricted mice exhibited growth delays that quickly caught up on return to standard diet. Between 6 and 18 wk of age, previously restricted mice exhibited sustained, programmed changes in feeding behaviors, reductions in total food intake, and increases in water intake and aerobic energy expenditure while maintaining normal body composition. Although having no effect in control mice, administration of the ganglionic blocker hexamethonium abolished the programmed increase in basal metabolic rate in previously restricted mice. Together these data indicate that early-life Na restriction can cause programmed changes in ingestive behaviors, autonomic function, and energy expenditure that persist well into adulthood.

The Influence of CPAP Therapy on Basal Metabolic Rate and Physical Activity in Obese Patients with Obstructive Sleep Apnea.

Energy balance in Obstructive Sleep Apnea (OSA), a disease closely related to obesity, is disturbed, and physical activity levels are impaired. The role of Continuous Positive Airway Pressure treatment (CPAP) in alleviating the disruptions mentioned above is questioned. The objective of this study is to explore changes in energy expenditure (EE) and physical activity (PA) in obese patients with OSA after CPAP treatment. An assessment of Basal Metabolic Rate (BMR) via indirect calorimetry (IC) was performed on 24 obese patients (male in the majority (87.5%), mean age of 52.4 ± 9.8 years), newly diagnosed with moderate-severe OSA by polysomnography, at 4-time points: at baseline, at CPAP titration, at the 1-month and the 3-month follow up. Physical activity levels were subjectively estimated using the International Questionnaire of Physical Activity (IPAQ) before and after 3 months of adherent CPAP application. BMR significantly decreased after CPAP treatment (1926 ± 537.8 kcal/d at baseline, 1790 ± 493.7 kcal/d at CPAP initiation, 1680.3 ± 600.8 kcal/d at 1 month, and 1581.3 ± 478.9 kcal/d at 3 months follow up (p < 0.001)). No significant changes in IPAQ were observed over time: baseline median IPAQ: 3894 (1487.5-11,755.5) total MET·min·wk-1, 3-month median IPAQ: 3900 (1512-11,824.5) total MET·min·wk-1. CPAP has an appreciable time effect on the BMR of obese patients with moderate-severe OSA. However, this change is not accompanied by a significant increase in physical activity levels.

Changes in Energy Expenditure Determined by Indirect Calorimetry in Severe Burn Patients During the Acute Phase.

Severe burn injuries are a major health problemglobally. A profound and prolonged hypermetabolic response develops in severe burn injuries and it is crucial to monitor the patients' energy requirements in order to meet them adequately.The aim of the present study was to examine the energy changes during the acute phase using the indirect calorimetry (IC) method in severe burn patients. The study included 15severe burn patients. Patients with FiO2>60%, tube thoracostomy, closed underwater drain (CUWD) and air leakage were excluded from the study. Patients' demographic data, burn percentages, burn types, duration of stay in intensive care, mortality and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were recorded. Indirect calorimeter measurements were taken once from the patients upon their first arrival and during the following four weeks. Resting energy expenditure (REE), basal metabolic rate (BMR), oxygen consumption (VO₂), carbon dioxide production (VCO₂), body temperatures, presence of sepsis, Sequential Organ Failure Assessment (SOFA) and Modified Nutrition Risk in Critically Ill (mNUTRIC) scores were recorded. The data were analysed usingSPSS 24and p-values <0.05 were considered statistically significant. In the study, 13 (86.67%) of the patients were male. Patients' mean age was 45.27±18.16 years, and mean BMI 25.99±4.22 kg/m2. Five patients (33.33%) had chronic diseases. The average burn percentage was 45%, with 7 (46.67%) patients having a burn percentage of ≤40%, while 8 (53.33%) had a burn percentage of >40%. A total of 14 (93.33%) had flame burns; 3 (20.00%) patients deceased, and 12 (80.00%) were discharged. The mean APACHE II score was 11.53±6.83. The measured mean values of REE, VO₂, VCO₂ and fever were seen to be the highest in the first week after admission and decreases were observed in the subsequent weeks. SOFA score averages were the highest at admission, and decreased in the following weeks. Severe burn patients were observed to go through the hypermetabolic process in the acute phase and their energy requirements were high particularly in the first week. It was concluded that regular IC monitoring can be beneficial to fully meet the energy requirements of severe burn patients due to the prolonged hypermetabolic process.

SAT002 Liver-specific Loss Of The Nuclear Receptor Co-regulator ARGLU1 Protects Against Diet-induced Obesity In Female Mice Independent Of Food Intake And Energy Expenditure

Abstract Disclosure: S.B. Cash: None. L. Magomedova: None. R. Tsai: None. C.L. Cummins: None. Arginine and glutamate rich 1 (ARGLU1) has been shown to be a co-regulator for several nuclear receptors including ER, GR and the peroxisome proliferator-activated receptors (PPARs), which are key modulators of nutrient metabolism. We have previously reported that loss of ARGLU1 in the liver protects aged male mice against high-fat diet induced obesity and type 2 diabetes [1]. Here, we assessed the importance of ARGLU1 in lipid and carbohydrate metabolism in aged female mice and used indirect calorimetry to understand the metabolic basis of the resistance to weight gain observed with liver-specific loss of ARGLU1. Aged (11-month-old) female wildtype floxed-Arglu1 mice (Arglu1fl/fl) and liver-specific Arglu1-null mice (Arglu1LKO) were fed a high fat, high cholesterol diet (HFD, 42% calories from fat, TD.88137 Envigo) for 12-weeks (N=7-17). Female mice were housed in Promethion Metabolic Cages (Sable Systems) at room temperature for 5 days during which their food intake, water intake, physical activity, O2 consumption, and CO2 production were measured (N=5-7). Female mice were also subjected to a glucose tolerance test and insulin tolerance test (N=4-8). In agreement with our previous results in male Arglu1LKO mice [1], female Arglu1LKO mice were resistant to diet-induced obesity with final body weights compared to HFD-fed Arglu1fl/fl mice of 30.6 ± 0.9 g vs 35 ± 1 g (P&amp;lt;0.05). Likewise, female Arglu1LKO mice were more glucose tolerant and insulin tolerant compared to HFD-fed Arglu1fl/fl mice. The metabolic cage data showed no change in food intake, locomotor activity or energy expenditure between HFD-fed Arglu1fl/fl and Arglu1LKO mice when accounting for body mass as a covariate (ANCOVA, CalR). Surprisingly, HFD-fed female Arglu1LKO mice had significantly higher water intake compared to HFD-fed Arglu1fl/fl mice (P&amp;lt;0.02). These data support the conclusion that resistance to diet-induced obesity in Arglu1LKO mice is independent of sex. To our surprise, based on the metabolic cage data, we conclude that the mechanism by which Arglu1LKO mice are resistant to diet induced obesity is not due to enhanced energy expenditure or decreased food intake. Future studies will explore whether differential intestinal lipid absorption (independent of food intake) could account for the differences we observed in weight gain between the genotypes. [1] Magomedova, L., Tsai, R., &amp; Cummins, C. L. (2017, April). Hepatic Ablation of the Nuclear Receptor Coactivator, ARGLU1, Is Protective Against the Development of Type 2 Diabetes and Fatty Liver in High-Fat Diet Fed Mice. In 99th Annual Meeting of the Endocrine Society. Endocrine Society. Presentation: Saturday, June 17, 2023

Circumventricular organ-hypothalamic circuit endoplasmic reticulum stress drives hepatic steatosis during obesity.

Nonalcoholic fatty liver disease (NAFLD), characterized by excess liver triglyceride accumulation (hepatic steatosis), leads to an increased risk for cardiometabolic diseases and obesity-related mortality. Emerging evidence points to endoplasmic reticulum (ER) stress in the central nervous system as critical in NAFLD pathogenesis. Here, we tested the contribution of ER stress in a circumventricular organ-hypothalamic circuit in NAFLD development during obesity. C57BL/6J male mice were fed a high-fat diet (HFD) or normal chow. A combination of histological, viral tracing, intersectional viral targeting, and in vivo integrative physiological approaches were used to examine the role of ER stress in subfornical organ to hypothalamic paraventricular nucleus projecting neurons (SFO➔PVN) in NAFLD during diet-induced obesity. Immunohistochemical analysis revealed marked unfolded protein response activation in the SFO, particularly in excitatory SFO➔PVN neurons of HFD-fed animals. Moreover, intersectional viral inhibition of ER stress in SFO➔PVN neurons resulted in a reduction in hepatomegaly, hepatic steatosis, and a blunted increase in body weight gain during diet-induced obesity, independent of changes in food intake, substrate partitioning, energy expenditure, and ambulatory activity. These results indicate that ER stress in an SFO➔PVN neural circuit contributes to hepatic steatosis during obesity.

Brown adipocyte mineralocorticoid receptor deficiency impairs metabolic regulation in diet-induced obese mice

Activation of brown adipose tissue (BAT) contributes to energy dissipation and metabolic health. Although mineralocorticoid receptor (MR) antagonists have been demonstrated to improve metabolism under obesity, the underlying mechanisms remain incompletely understood. We aimed to evaluate the role of BAT MR in metabolic regulation. After 8 weeks of high-fat diet (HFD) feeding, BAT MR KO (BMRKO) mice manifested significantly increased bodyweight, fat mass, serum fasting glucose, and impaired glucose homeostasis compared with littermate control (LC) mice, although insulin resistance and fasting serum insulin were not significantly changed. Metabolic cage experiments showed no change in O2 consumption, CO2 production, or energy expenditure in obese BMRKO mice. RNA sequencing analysis revealed downregulation of genes related to fatty acid metabolism in BAT of BMRKO-HFD mice compared with LC-HFD mice. Moreover, H&E and immunohistochemical staining demonstrated that BMRKO exacerbated HFD-induced macrophage infiltration and proinflammatory genes in epididymal white adipose tissue (eWAT). BMRKO-HFD mice also manifested significantly increased liver weights and hepatic lipid accumulation, an increasing trend of genes related to lipogenesis and lipid uptake, and significantly decreased genes related to lipolytic and fatty acid oxidation in the liver. Finally, the level of insulin-induced AKT phosphorylation was substantially blunted in eWAT but not liver or skeletal muscle of BMRKO-HFD mice compared with LC-HFD mice. These data suggest that BAT MR is required to maintain metabolic homeostasis, likely through its regulation of fatty acid metabolism in BAT and impacts on eWAT and liver.