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Systemic glucocorticoid excess causes several adverse metabolic conditions, most notably Cushing's syndrome. These effects are amplified by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Here, we determined the less well-characterised effects of glucocorticoid excess, and the contribution of 11β-HSD1 amplification on metabolic rate in mice. Male and female C57BL/6J (wild type, WT) and 11β-HSD1 knockout (11β-HSD1 KO) mice were treated with high-dose corticosterone or a vehicle control for 3 weeks. Indirect calorimetry was conducted during the final week of treatment, with or without fasting, to determine the impact on metabolic rate. We found that corticosterone treatment elevated metabolic rate and promoted carbohydrate utilisation primarily in female WT mice, with effects more pronounced during the light phase. Corticosterone treatment also resulted in greater fat accumulation in female WT mice. Corticosterone induced hyperphagia was identified as a likely causal factor altering the respiratory exchange ratio (RER) but not energy expenditure (EE). Male and female 11β-HSD1 KO mice were protected against these effects. We identify novel metabolic consequences of sustained glucocorticoid excess, identify a key mechanism of hyperphagia, and demonstrate that 11β-HSD1 is required to manifest the full metabolic derangement.

Many of the negative physiological effects of lead involve the hypothalamus, but the possibility that thermoregulation is affected has received little attention. We tested the hypothesis that lead exposure reduces avian thermoregulatory performance under hot conditions in pied crows (Corvus albus) experimentally exposed to lead in their diet. Crows in our high lead treatment (blood [Pb] = 87.3 ± 44.7 μg dL -1 ) showed significantly higher air temperature (T air ) inflections for evaporative water loss (EWL) and resting metabolic rate (RMR) compared to control (6.4 ± 1.8 μg dL -1 ) or intermediate (53.9 ± 23.7 μg dL -1 ) lead groups, which did not differ. EWL, RMR and body temperature (T b ) all increased more rapidly at T air > T b in the high lead treatment. In contrast, neither maximum T air tolerated by the crows nor maximum T b varied with treatment. Our data reveal that water and energy balance during hot weather is affected by lead exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Bifidobacterium animalis subsp. lactis GCL2505 in combination with inulin has been shown to have several health benefits, including an improvement in the intestinal microbiota and a reduction in human visceral fat. Previous studies have suggested that the visceral fat reduction of GCL2505 and inulin may be achieved by improving daily energy expenditure. This parallel, placebo-controlled, randomized, double-blind study was conducted to evaluate the effects of GCL2505 and inulin on resting energy expenditure (REE) in overweight or mildly obese Japanese adults ( n = 44). Participants ingested 1 × 10 10 colony forming units of GCL2505 and 5.0 g of inulin daily for 4 weeks. REE score at week 4 was set as the primary endpoint. At week 4, the REE score of the GCL2505 and inulin group was significantly higher than that of the placebo group, with a difference of 84.4 kcal/day. In addition, fecal bifidobacteria counts were significantly increased in the GCL2505 and inulin group. Our results indicated that the intake of GCL2505 and inulin improves energy balance, which is known to be a major factor of obesity, by modulating the microbiota in the gut. This is the first report to demonstrate the effects of probiotics and dietary fiber on REE in humans.

Organisms regularly adjust their physiology and energy balance in response to predictable seasonal environmental changes. Stressors and contaminants have the potential to disrupt these critical seasonal transitions. No studies have investigated how simultaneous exposure to the ubiquitous toxin methylmercury (MeHg) and food stress affects birds' physiological performance across seasons. We quantified several aspects of energetic performance in song sparrows, Melospiza melodia, exposed or not to unpredictable food stress and MeHg in a 2×2 experimental design, over 3 months during the breeding season, followed by 3 months post-exposure. Birds exposed to food stress had reduced basal metabolic rate and non-significant higher factorial metabolic scope during the exposure period, and had a greater increase in lean mass throughout most of the experimental period. Birds exposed to MeHg had increased molt duration, and increased mass:length ratio of some of their primary feathers. Birds exposed to the combined food stress and MeHg treatment often had responses similar to the stress-only or MeHg-only exposure groups, suggesting these treatments affected physiological performance through different mechanisms and resulted in compensatory or independent effects. Because the MeHg and stress variables were selected in candidate models with a ΔAICc lower than 2 but the 95% confidence interval of these variables overlapped zero, we found weak support for MeHg effects on all measures except basal metabolic rate, and for food stress effects on maximum metabolic rate, factorial metabolic scope and feather mass:length ratio. This suggests that MeHg and food stress effects on these measures are statistically identified but not simple and/or were too weak to be detected via linear regression. Overall, combined exposure to ecologically relevant MeHg and unpredictable food stress during the breeding season does not appear to induce extra energetic costs for songbirds in the post-exposure period. However, MeHg effects on molt duration could carry over across multiple annual cycle stages., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The purpose of this study was to investigate the effects of a novel dietary supplement, including melatonin and magnesium, delivered via coffee pods on sleep quality, resting metabolic rate (RMR), and body composition in individuals with poor sleep quality disturbances. Using a double-blinded, randomized, crossover trial, we recruited 35 participants to a 4-week intervention with both supplements (1.9 mg melatonin + 200 mg elemental magnesium before sleep) and placebo conditions, considering a 7d washout period between treatments. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was applied, RMR (kcal) was measured using indirect calorimetry (canopy ventilated open-circuit system) and body composition was assessed using dual-energy X-ray absorptiometry. Decreases in PSQI and anger - hostility scores, as well as in energy intake and fat mass, were observed ( p  < 0.05) for both conditions, from baseline to the end of each 4-week intervention. Differences between conditions were also observed for these parameters along with energy spent in activity, number of sedentary breaks, sleep efficiency, latency time, time in bed, total sleep time, awakening time, and movement index ( p  < 0.05) favouring the supplement condition. However, the final PSQI questionnaire scores still indicated poor sleep quality on average (PSQI > 5), in both conditions, with no changes regarding RMR. A melatonin-magnesium supplement, in a coffee pod format, showed improvements in sleep quality in otherwise healthy individuals with sleep disturbances, however PSQI questionnaire scores still indicated poor quality on average (PSQI > 5).

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise.

We examined the association among basal metabolic rate (BMR) as well as dietary intakes of vitamin D (Vit D) and calcium on body composition and bone mineral density (BMD) after spinal cord injury (SCI). Cross-sectional design. Veterans Affairs Medical Center, Richmond, VA. About 33 individuals with chronic SCI who recorded their food consumption 3 days per week for 2 weeks. BMR was measured after 10 to 12 h of overnight fast. Average daily vit D and calcium intakes, and total caloric intake were recorded and analyzed using the Nutrition Data System for Research (NDSR) software. Fasting blood analysis for 25-hydroxyvitamin D (25[OH]D) status and Triiodothyronine (T3) status was performed (n = 10). Total and regional BMD, % fat mass (FM), and % lean mass (LM) were measured by dual X-ray absorptiometry scans. Participants consumed less than the Institute of Medicine (IOM) recommended daily allowances (RDA) for vit D (600-800 IU) and calcium (1000-1200 mg) for adults. BMR was positively related to total-lean mass ( r  = .62, P  = .0001; n = 32) and leg-lean mass ( r  = .51, P  = .003; n = 32). Adjusted BMR was negatively related to BMD of the left (r = -.38, P  = .047; n = 28) and the right (r = -.41, P  = .032; n = 28) proximal tibia. Vit D intake was negatively related to percentage total-FM ( r  = -.33, P  = .07; n = 29) and legs-%FM ( r  = -.37, P  = .047; n = 29). Multivariate regression models indicated that adjusted BMR explained the variance in leg fat mass (34%; P  = .002) and percentage fat mass (44%; P  < .0001). Persons with SCI are likely to consume less than the RDAs for vit D and calcium. BMR may explain the changes in body composition and bone metabolism. Dietary vit D should be considered as a prophylactic intervention in maintenance of bone health after SCI., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chronic elevation of circulating cortisol is known to have deleterious effects on fish, but information about the consequences of prolonged cortisol elevation on the metabolism of fish is scarce. To test the effects of chronic cortisol elevation on the aerobic performance of rainbow trout, we examined how two severities of chronically elevated plasma cortisol levels affected the oxygen uptake during rest and after exhaustive exercise using a high (HC) and a medium cortisol (MC) treatment. High cortisol doses significantly affected standard (SMR) and maximum metabolic rates (MMR) compared to control fish. In comparison, the medium cortisol treatment elevated maximum metabolic rates (MMR) but did not significantly influence SMR compared to a sham group (S) and control group (C). The medium cortisol treatment resulted in a significantly increased metabolic scope due to an elevation of MMR, an effect that was abolished in the HC group due to co-occuring elevations in SMR. The elevated SMR of the HC-treated fish could be explained by increased in vitro oxygen uptake rates (MO 2 ) of specific tissues, indicating that the raised basal metabolism was caused, in part, by an increase in oxygen demand of specific tissues. Haematological results indicated an increased reliance on anaerobic metabolic pathways in cortisol-treated fish under resting conditions., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Branched chain amino acids (BCAA) supplementation is reported to aid in lean mass preservation, which may in turn minimize the reduction in resting metabolic rate (RMR) during weight loss. Our study aimed to examine the effect of BCAA supplementation to a hypocaloric diet on RMR and substrate utilization during a weight loss intervention., Methods: A total of 111 Chinese subjects comprising 55 males and 56 females aged 21 to 45 years old with BMI between 25 and 36 kg/m 2 were randomized into three hypocaloric diet groups: (1) standard-protein (14%) with placebo (CT), (2) standard-protein with BCAA, and (3) high-protein (27%) with placebo. Indirect calorimetry was used to measure RMR, carbohydrate, and fat oxidation before and after 16 weeks of dietary intervention., Results: RMR was reduced from 1600 ± 270 kcal/day to 1500 ± 264 kcal/day ( p < 0.0005) after weight loss, but no significant differences in the change of RMR, respiratory quotient, and percentage of fat and carbohydrate oxidation were observed among the three diet groups. Subjects with BCAA supplementation had an increased postprandial fat ( p = 0.021) and decreased postprandial carbohydrate ( p = 0.044) oxidation responses compared to the CT group after dietary intervention., Conclusions: BCAA-supplemented standard-protein diet did not significantly attenuate reduction of RMR compared to standard-protein and high-protein diets. However, the postprandial fat oxidation response increased after BCAA-supplemented weight loss intervention.

Background: Previous studies have shown that the minor allele (C allele) for Cry 1 rs2287161, may be associated with increased risk of cardiovascular diseases (CVDs). Low resting metabolic rate (RMR) caused by the diet has been shown to have, potentially, unfavorable effects on obesity. This study sought to investigate the interactions between the Cry 1 Gene and fat intake on RMR in women with overweight of obesity., Methods: This comparative cross-sectional study was conducted on 377 Iranian women with overweight of obesity. A food frequency questionnaire (FFQ), with 147 items, was used to assess dietary intake. Individuals were categorized into two groups based on the rs2287161 genotype. Body composition, dietary intake, and RMR were assessed for all participants., Results: There was a significant difference between genotypes for fasting blood sugar (FBS) (P = 0.04), fat free mass (FFM) (P = 0.0009), RMR per FFM (P = 0.05), RMR per body mass index (BMI) (P = 0.02), and RMR deviation (P = 0.01). Our findings also showed significant interactions between total fat and C allele carrier group on RMR per kg body weight, RMR per body surface area (BSA), RMR per FFM, and RMR deviation (P for interaction < 0.1), in addition to a significant interaction between CC + CG group genotype and polyunsaturated fatty acids (PUFA) intake on RMR per BMI (P for interaction =0.00) and RMR per kg (P for interaction = 0.02) and RMR per BSA (P = 0.07), compared to the GG group, after control for confounder factors., Conclusion: These results highlight that dietary compositions, gene variants, and their interaction, should be acutely considered in lower RMR., (© 2021. The Author(s).)

Metformin can reduce cardiovascular risk independent of glycemic control. The mechanisms behind its non-glycemic benefits, which include decreased energy intake, lower blood pressure and improved lipid and fatty acid metabolism, are not fully understood. In our study, metformin treatment reduced myocardial accumulation of neutral lipids-triglycerides, cholesteryl esters and the lipotoxic intermediates-diacylglycerols and lysophosphatidylcholines in a prediabetic rat model ( p < 0.001). We observed an association between decreased gene expression and SCD-1 activity ( p < 0.05). In addition, metformin markedly improved phospholipid fatty acid composition in the myocardium, represented by decreased SFA profiles and increased n3-PUFA profiles. Known for its cardioprotective and anti-inflammatory properties, metformin also had positive effects on arachidonic acid metabolism and CYP-derived arachidonic acid metabolites. We also found an association between increased gene expression of the cardiac isoform CYP2c with increased 14,15-EET ( p < 0.05) and markedly reduced 20-HETE ( p < 0.001) in the myocardium. Based on these results, we conclude that metformin treatment reduces the lipogenic enzyme SCD-1 and the accumulation of the lipotoxic intermediates diacylglycerols and lysophosphatidylcholine. Increased CYP2c gene expression and beneficial effects on CYP-derived arachidonic acid metabolites in the myocardium can also be involved in cardioprotective effect of metformin.

The purpose of the present study was to compare next-morning responses of RMR and appetite to pre-sleep consumption of casein protein (CP) in pre- and postmenopausal women. The study was a randomised, crossover, double-blind, placebo-controlled trial. Seven sedentary premenopausal (age: 19·9 (sd 1·2) years; BMI: 23·1 (sd 2·6) kg/m2) and seven sedentary postmenopausal (age: 56·4 (sd 4·9) years; BMI: 26·3 (sd 3·5) kg/m2) women participated. During visit one, anthropometrics and body composition were measured. Following visit one, subjects consumed either CP (25 g) or placebo (PL) ≥2 h after their last meal and ≤30 min prior to sleep on the night before visits two and three. Visits two and three occurred ≥1 week after visit one and were 48 h apart. During visits two and three, RMR (VO2), RER and appetite were measured via indirect calorimetry and visual analogue scale, respectively. Anthropometrics and body composition were analysed by one-way ANOVA. RMR and measures of appetite were analysed using a 2 × 2 (menopause status × CP/PL) repeated-measures ANOVA. Significance was accepted at P ≤ 0·05. RMR was significantly lower in postmenopausal compared with premenopausal women under both conditions (P = 0·003). When consumed pre-sleep CP did not alter RMR, RER or appetite compared with PL when assessed next morning in pre- and postmenopausal women. These data contribute to growing evidence that pre-sleep consumption of protein is not harmful to next-morning metabolism or appetite. In addition, these data demonstrate that menopause may not alter next-morning RMR, RER or appetite after pre-sleep consumption of CP.

While exercise training (ET) is an efficient strategy to manage obesity, it is recommended with a dietary plan to maximize the antiobesity functions owing to a compensational increase in energy intake. Capsiate is a notable bioactive compound for managing obesity owing to its capacity to increase energy expenditure. We aimed to examine whether the antiobesity effects of ET can be further enhanced by capsiate intake (CI) and determine its effects on resting energy expenditure and metabolic molecules. Mice were randomly divided into four groups ( n = 8 per group) and fed high-fat diet. Mild-intensity treadmill ET was conducted five times/week; capsiate (10 mg/kg) was orally administered daily. After 8 weeks, resting metabolic rate and metabolic molecules were analyzed. ET with CI additively reduced the abdominal fat rate by 18% and solely upregulated beta-3-adrenoceptors in adipose tissue ( p = 0.013) but did not affect the metabolic molecules in skeletal muscles. Surprisingly, CI without ET significantly increased the abdominal fat rate ( p = 0.001) and reduced energy expenditure by 9%. Therefore, capsiate could be a candidate compound for maximizing the antiobesity effects of ET by upregulating beta-3-adrenoceptors in adipose tissue, but CI without ET may not be beneficial in managing obesity.

Dioxin exposure during bird embryonic development disrupts immunity as well as mechanisms involved in energy metabolism, potentially affecting negatively acute-phase responses to pathogens. Thus, we hypothesized that embryonic exposure to 2,3,7,8-tetrachlorodibenzodioxin (TCDD) changes the metabolism and blood physiology of domestic chicks, affecting their physiological competence for responding to immune challenges. To test this hypothesis, we injected doses of 0, 1.5, and 3 ng TCDD/egg (based on survival experiments) on embryonic day 4 and then measured O 2 consumption and CO 2 production for metabolic rate, ventilation, and body temperature (T B ) in 5-d-old chicks. Then, chicks were injected with lipopolysaccharide (LPS, endotoxin) or saline prior to repeating the physiological measurements. A second chick group exposed to identical TCDD and LPS treatments had blood partial pressure of oxygen, partial pressure of carbon dioxide, pH, bicarbonate concentration, lactate concentration, osmolality, hemoglobin concentration, red blood cell concentration, and hematocrit, as well as T B , analyzed at 1 and 5 h after LPS injection. Metabolism in chicks embryonically exposed to 1.5 and 3 ng TCDD/egg was up to 37% higher, whereas body mass of chicks exposed to 3 ng TCDD/egg was approximately 6% lower. Chicks embryonically exposed to 3 ng TCDD/egg challenged with LPS showed a relative persistent hypometabolism accompanied by elimination of the normal hematological and osmotic responses to LPS. We conclude that embryonic exposure to TCDD affects posthatching metabolism as well as impairs metabolic, hematological, and osmotic responses to LPS. Environ Toxicol Chem 2020;39:2208-2220. © 2020 SETAC., (© 2020 SETAC.)

Supplementation with the most efficient form of Vitamin D (VitD3) results in improvements in energy metabolism, muscle mass and strength in VitD deficient individuals. Whether similar outcomes occur in VitD sufficient individuals' remains to be elucidated. The aim of this study is to determine the effect of VitD3 supplementation on resting metabolic rate (RMR), body composition and strength in VitD sufficient physically active young adults. Participants completed pre-supplementation testing before being matched for sunlight exposure and randomly allocated in a counterbalanced manner to the VitD3 or placebo group. Following 12 weeks of 50 IU/kg body-mass VitD3 supplementation, participants repeated the pre-supplementation testing. Thirty-one adults completed the study (19 females and 12 males; mean ± standard deviation (SD); age = 26.6 ± 4.9 years; BMI = 24.2 ± 4.1 kg·m 2 ). The VitD group increased serum total 25(OH)D by 30 nmol/L while the placebo group decreased total serum concentration by 21 nmol/L, reaching 123 (51) and 53 (42.2) nmol/L, respectively. There were no significant changes in muscle strength or power, resting metabolic rate and body composition over the 12-week period. Physically active young adults that are VitD sufficient have demonstrated that no additional physiological effects of achieving supraphysiological serum total 25(OH)D concentrations after VitD3 supplementation., Competing Interests: The authors declare no conflict of interest.

Numerous epidemiological studies have reported that moderate alcohol drinking has beneficial effects. However, few studies have focused on the beneficial effects of ethanol, the common component in alcoholic beverages. Here we fed the C57BL/6 mice with 3.5% v/v ethanol as drinking water substitute to investigate the effects of long-term low-dose ethanol intake in vivo . We evaluated the metabolic rate and mitochondrial function of the long-term low-dose ethanol-intake (LLE) mice, assessed the exercise ability of LLE mice, and fed the LLE mice with a high-fat diet to investigate the potential impact of ethanol on it. The LLE mice showed improved thermogenic activity, physical performance, and mitochondrial function, as well as resistance against the high-fat diet-induced obesity with elevated insulin sensitivity and subdued inflammation. Our results suggest that long-term low-dose ethanol intake can improve healthspan and resist high-fat diet-induced obesity in mice. It may provide new insight into understanding the protective effects of moderate alcohol drinking.

The aim of the present study was to determine the effect of zearalenone (ZEN), administered per os to gilts at doses equivalent to 50%, 100%, and 150% of no-observed-adverse-effect level (NOAEL) values for 14, 28, and 42 days during weaning, on changes in the parameters of the oxidoreductive balance, cytokine secretion, and basal metabolism in ileal Payer's patches. Immunoenzymatic ELISA tests and biochemical methods were used to measure the concentrations of interleukin 1α, interleukin 1β, interleukin 12/23p40, interleukin 2, interferon γ, interleukin 4, interleukin 6, interleukin 8, tumor necrosis factor α, interleukin 10, transforming growth factor β, malondialdehyde, sulfhydryl groups, fructose, glucose, and proline, as well as the activity of peroxidase, superoxide dismutase and catalase. The study demonstrated that ZEN doses corresponding to 50%, 100%, and 150% of NOAEL values, i.e., 5 µg, 10 µg, and 15 µg ZEN/kg BW, respectively, have proinflammatory properties, exacerbate oxidative stress responses, and disrupt basal metabolism in ileal Payer's patches in gilts.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a new family of endogenous lipids recently discovered. Several studies reported that some FAHFAs have antidiabetic and anti-inflammatory effects. The objective of this study was to explore the impact of two FAHFAs, 9-PAHPA or 9-OAHPA, on the metabolism of mice. C57Bl/6J male mice, 6 weeks old, were divided into 3 groups of 10 mice each. One group received a control diet and the two others groups received the control diet supplemented with 9-PAHPA or 9-OAHPA for 12 weeks. Mouse weight and body composition were monitored throughout the study. Some days before euthanasia, energy expenditure, glucose tolerance and insulin sensitivity were also determined. After sacrifice, blood and organs were collected for relevant molecular, biochemical and histological analyses. Although high intake of 9-PAHPA or 9-OAHPA increased basal metabolism, it had no direct effect on body weight. Interestingly, the 9-PAHPA or 9-OAHPA intake increased insulin sensitivity but without modifying glucose tolerance. Nevertheless, 9-PAHPA intake induced a loss of glucose-stimulated insulin secretion. Surprisingly, both studied FAHFAs induced hepatic steatosis and fibrosis in some mice, which were more marked with 9-PAHPA. Finally, a slight remodeling of white adipose tissue was also observed with 9-PAHPA intake. In conclusion, the long-term high intake of 9-PAHPA or 9-OAHPA increased basal metabolism and insulin sensitivity in healthy mice. However, this effect, highly likely beneficial in a diabetic state, was accompanied by manifest liver damage in certain mice that should deserve special attention in both healthy and pathological studies., Competing Interests: Conflict of interest The authors confirm that this article content has no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Estrogen-responsive breast cancer cells exhibit both basal and estrogen-regulated transcriptional programs, which lead to the transcription of many different transcription units (i.e., genes), including those that produce coding and non-coding sense (e.g., mRNA, lncRNA) and antisense (i.e., asRNA) transcripts. We have previously characterized the global basal and estrogen-regulated transcriptomes in estrogen receptor alpha (ERα)-positive MCF-7 breast cancer cells. Herein, we have mined genomic data to define three classes of antisense transcription in MCF-7 cells based on where their antisense transcription termination sites reside relative to their cognate sense mRNA and lncRNA genes. These three classes differ in their response to estrogen treatment, the enrichment of a number of genomic features associated with active promoters (H3K4me3, RNA polymerase II, open chromatin architecture), and the biological functions of their cognate sense genes as analyzed by DAVID gene ontology. We further characterized two estrogen-regulated antisense transcripts arising from the MYC gene in MCF-7 cells, showing that these antisense transcripts are 5'-capped, 3'-polyadenylated, and localized to different compartments of the cell. Together, our analyses have revealed distinct classes of antisense transcription correlated to different biological processes and response to estrogen stimulation, uncovering another layer of hormone-regulated gene regulation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Two recent studies challenged traditional paradigms of mammalian sodium physiology, suggesting that sodium reduction might cause weight gain by altering metabolism. This new theory has important implications for population-wide dietary recommendations. However, these observations have not been confirmed. In the DASH (Dietary Approaches to Stop Hypertension)-Sodium trial, 412 adults with systolic blood pressure of 120 to 159 mm Hg and diastolic blood pressure of 80 to 95 mm Hg not taking antihypertensive medications were randomly assigned to the DASH diet or a control diet (parallel design). On their assigned diet, participants randomly consumed each of the 3 sodium levels for 4 weeks (crossover design). Participants were provided all meals but could drink noncaloric beverages (eg, water) freely. Throughout the trial, energy intake was adjusted to maintain weight constant. The 3 sodium levels (at 2100 kcal/day) were: low (1150 mg of Na/day), medium (2300 mg of Na/day), and high (3450 mg of Na/day). Energy intake, weight, self-reported thirst, and 24-hour urine volume were assessed after each period. Participants were 57% women and 57% black; mean age was 48 years [SD, 10]). Among those assigned the control, mean weight increased slightly with higher sodium but not among those assigned DASH. Energy intake did not vary across sodium levels in either diet ( P -trends ≥0.36). Higher sodium resulted in more thirst ( P -trends <0.001 on both diets) and higher urine volume (suggesting higher fluid intake) during the control diet ( P -trend=0.007). Reducing sodium did not increase energy requirements to maintain stable weights but did decrease thirst and urine volume (control diet only), findings consistent with the traditional understanding of mammalian sodium physiology. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000608.

Our studies in primary human adipocytes show that naringenin, a citrus flavonoid, increases oxygen consumption rate and gene expression of uncoupling protein 1 (UCP1), glucose transporter type 4, and carnitine palmitoyltransferase 1 β (CPT1 β ). We investigated the safety of naringenin, its effects on metabolic rate, and blood glucose and insulin responses in a single female subject with diabetes. The subject ingested 150 mg naringenin from an extract of whole oranges standardized to 28% naringenin three times/day for 8 weeks, and maintained her usual food intake. Body weight, resting metabolic rate, respiratory quotient, and blood chemistry panel including glucose, insulin, and safety markers were measured at baseline and after 8 weeks. Adverse events were evaluated every 2 weeks. We also examined the involvement of peroxisome proliferator-activated receptor α (PPAR α ), peroxisome proliferator-activated receptor γ (PPAR γ ), protein kinase A (PKA), and protein kinase G (PKG) in the response of human adipocytes to naringenin treatment. Compared to baseline, the body weight decreased by 2.3 kg. The metabolic rate peaked at 3.5% above baseline at 1 h, but there was no change in the respiratory quotient. Compared to baseline, insulin decreased by 18%, but the change in glucose was not clinically significant. Other blood safety markers were within their reference ranges, and there were no adverse events. UCP1 and CPT1β mRNA expression was reduced by inhibitors of PPAR α and PPAR γ , but there was no effect of PKA or PKG inhibition. We conclude that naringenin supplementation is safe in humans, reduces body weight and insulin resistance, and increases metabolic rate by PPAR α and PPAR γ activation. The effects of naringenin on energy expenditure and insulin sensitivity warrant investigation in a randomized controlled clinical trial.

Aims: To investigate predictors of the initial response of beta-hydroxybutyrate (BHB) and maximum BHB (max-BHB) values during long-term therapy with the sodium-glucose co-transporter-2 inhibitor tofogliflozin (TOFO), and to explore the association of the initial elevation of BHB with subsequent clinical effects in people with type 2 diabetes mellitus., Methods: We analysed 774 people receiving TOFO in phase 3 trials in two groups based on measurable BHB change at week 4 (initial response): the top quartile [n = 194] and the three lower quartiles [n = 579]. Multivariate analysis was used to determine baseline predictors of inclusion in the top quartile and the max-BHB values. To investigate the association of the initial response with subsequent clinical effects, adjusted changes in variables in the two groups were compared using an analysis of covariance model., Results: Of the participants, 66% were men, and the mean age, glycated haemoglobin, body mass index and estimated glomerular filtration rate were 58.5 years, 8.1%, 25.6 kg/m 2 and 83.9 mL/min/1.73 m 2 , respectively. Median changes in BHB at week 4 in the top quartile and lower three quartiles were +246.4* and +30.8* μmol/L, respectively (*P < .001 vs baseline). Lower baseline insulin secretion capacity predicted the inclusion in the top quartile and greater max-BHB levels. The top quartile was associated with greater weight loss following greater increases in free fatty acids and greater reductions in fasting C-peptide levels compared with the lower three quartiles., Conclusions: Lower basal insulin secretion capacity might predict greater initial BHB elevations and max-BHB levels during long-term TOFO therapy. Greater weight loss through lipid use might be related to high initial BHB elevations., (© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Males seeking to improve body composition may ingest thermogenic dietary supplements with the goal of elevating resting metabolic rate. The purpose of this study was to examine the effects of a commercially available dietary supplement (containing ingredients that promote thermogenesis) on resting metabolic rate (RMR) in a randomized, double-blind, placebo-controlled cross-over study. Ten healthy, physically active males (age: 26.5 ± 6.4 years; height: 177.6 ± 7.2 cm; body weight: 80.5 ± 10.8 kg) underwent two testing sessions separated by approximately 7 days. Following baseline assessments of RMR, heart rate (HR), and blood pressure (BP), each participant ingested a thermogenic dietary supplement or a placebo. Assessments were repeated at 60, 120, and 180 minutes postingestion. Approximately 1 week later, participants ingested the alternative supplement and the assessments were repeated. Post hoc analyses revealed that the dietary supplement treatment demonstrated significant elevations in RMR during the postingestion period ( p < 0.05) from 1,859 ± 266 kcal to 2,027 ± 288 kcal (increase of 9%) to 2,072 ± 292 kcal (increase of 11.5%) and to 2,040 ± 271 kcal (increase of 9.7%) at 60, 120, and 180 minutes postingestion, respectfully. No significant elevations were observed in the placebo treatment at any time point. HR and BP measures were within normal clinical values throughout the intervention.

Exposure to endocrine disrupting chemicals has been suggested to contribute to the ongoing globally increasing obesity trend. The complex chemical mixtures that humans and wildlife are exposed to include a number of compounds that may have obesogenic properties. In this study we examined a mixture consisting of phthalate-monoesters, triclosan, and perfluorinated compounds. The mixture was designed within the EDC-MixRisk project based on serum levels of the compounds in pregnant women of a Swedish mother-child cohort. The compounds were negatively associated with birth weight of the children. We assessed whether developmental exposure to this mixture in combination with a calorie-rich diet affected metabolic rate, blood lipids, adipogenesis and lipid storage, and the whole-body level of neutral lipids in zebrafish (Danio rerio). Wildtype zebrafish were exposed to the mixture from 3 h post fertilization to 5, 14 or 17 days post fertilization (dpf) at water concentrations corresponding to 1, 10, 20, or 100 times the geometrical mean of the serum concentration (hsc) in the women. Exposure to the mixture at 20 times hsc lowered metabolic rate at 2-5 dpf, and increased the number of adipocytes and the amount of visceral adipose tissue at 14 and 17 dpf respectively. Also, mRNA expression of fatty acid binding protein 11a was increased at 17 dpf by 10 and 20 times hsc of the mixture. This study shows that a human-relevant mixture of environmental pollutants affects metabolic rate, adipogenesis and lipid storage in young zebrafish fed a calorie-rich diet, thus demonstrating its potential to disrupt metabolism., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Maintaining adequate daily protein intake is important to maintain muscle mass throughout the lifespan. In this regard, the overnight period has been identified as a window of opportunity to increase protein intake in the elderly. However, it is unknown whether pre-sleep protein intake affects next-morning appetite and, consequently, protein intake. Therefore, the purpose of the current study was to investigate the effects of a pre-sleep protein drink on next-morning appetite, energy intake and metabolism. Twelve older individuals (eight males, four females; age: 71.3 ± 4.2 years) took part in a single-blind randomised cross-over study. After a standardised dinner, participants consumed either a 40-g protein drink, isocaloric maltodextrin drink, or placebo water control before bedtime. Next-morning appetite, energy intake, resting metabolic rate (RMR), respiratory exchange rate (RER), and plasma acylated ghrelin, leptin, glucose, and insulin concentrations were assessed. No between-group differences were observed for appetite and energy intake at breakfast. Furthermore, RMR, RER, and assessed blood markers were not significantly different between any of the treatment groups. Pre-sleep protein intake does not affect next-morning appetite and energy intake and is therefore a viable strategy to increase daily protein intake in an older population.

Although many studies have shown that histamine and its signaling regulate energy homeostasis through the central nervous system, their roles in adipose tissues remain poorly understood. Here, we identified that the histamine H4 receptor (HrH4) was highly expressed in adipocytes at a level higher than that of the other three receptors (i.e., HrH1, HrH2, and HrH3). The HrH4 expression in adipocytes responded to cold through thermogenesis and lipolysis, supported by results from both mouse and cell models. When HrH4 expression was knocked down in the subcutaneous white adipose tissue (scWAT), browning and lipolysis effects triggered by cold were ablated, and the oxygen consumption was also lowered both at the normal and cold conditions. Moreover, mice exhibited browned scWAT, accelerated metabolic rates, and tolerance to hypothermia when 4-methylhistamine (4MH), a selective HrH4 agonist, was adjacently injected to the scWAT. Consistent with these findings, 4MH also triggered the browning and lipolytic effects in cultured C3H10T1/2 adipocytes. Mechanically, we demonstrated that p38/MAPK and ERK/MAPK pathways were involved in these processes. In conclusion, our findings have uncovered an effective role of HrH4 in adipose tissue browning.

Whole-organism metabolism is an integrative process that determines not only the energy cost of living but also the energy output that is available for behavioral and physiological processes during the life cycle. Developmental challenge is known to affect growth, development of several organs, and several physiological mechanisms (such as HPA responsiveness, oxidative stress or immunity), which may altogether affect adult metabolism. All of these developmental effects are likely to be mediated by glucocorticoids, but the impact of developmental glucocorticoid exposure on adult metabolism has rarely been studied and the results are equivocal. In this study, we examined the impact of developmental exposure to corticosterone (CORT, the main avian glucocorticoid hormone) on resting metabolic rate (RMR, measured in thermoneutrality, 25°C) and thermoregulatory metabolic rate (TMR, measured in cold challenge conditions, 5°C) in the house sparrow. Following experimental administration of CORT at the nestling stage, house sparrows were kept in captivity until adulthood, when their metabolism was measured. We found that post-natal CORT exposure decreased both RMR and TMR in adult sparrows. This CORT-mediated reduction of metabolism was also associated with a reduced overnight body mass loss. Therefore, our results suggest that developmental CORT exposure can orient the phenotype towards an energy-saving strategy, which may be beneficial in a constraining environmental context., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

To investigate changes in resting metabolic rate and 8-isoprostane, an oxidative stress biomarker, following acute dietary nitrate supplementation in healthy males and females. In a randomised, double-blind, cross-over study, 10 males and seven females (age range 19-25 years) underwent protocol familiarisation (visit 1), baseline assessments (visits 2 and 4) and assessments following supplementation, placebo or 6.2 mmol nitrate, 2 hours prior to visits 3 and 5. Participants completed a 30-minute RMR test with visits 2 and 3 on consecutive days, separated by a week-long washout period concluding with visits 4 and 5 on consecutive days. Plasma nitrate/nitrite (NOx) significantly increased ( p  ≤ 0.05) following dietary nitrate consumption compared to baseline values. No significant effect on resting metabolism ( p  = 0.194) or 8-isoprostane ( p  = 0.660) was observed following dietary nitrate supplementation. Dietary nitrate increases NO bioavailability, but acute supplementation does not effect resting metabolism or 8-isoprostane in healthy males and females.

The photoperiodic response of many temperate zone rodents, including white-footed mice (Peromyscus leucopus), is a heritable life-history trait with underlying physiological variation. Previous studies of intact male P. leucopus utilized two wild-derived bidirectional selection lines, a short photoperiod responsive (R) line selected for reproductive suppression in short-day conditions (SD) and a nonresponsive (NR) line selected for reproductive maturity in SD. NR mice in SD had greater food intake, but also higher levels of locomotor activity, and basal metabolic rate (BMR) than R mice. We hypothesized that testosterone may be a key mediator of this metabolic difference, as it is likely to be significantly reduced in R SD mice. Male P. leucopus from either line in SD were castrated and given either an implant containing testosterone (T) or a sham control (C). They were then tested for variation in metabolic rate and activity in SD, thermoneutral conditions. T mice had significantly higher levels of food intake, testosterone, and seminal vesicle dry weight than C mice. Seminal vesicle dry weight was significantly and positively correlated with average testosterone level, indicating an effect of the T implants. There was no statistically significant difference among treatment groups in BMR and average daily metabolic rate, suggesting that differences in testosterone alone are not the cause of differences in metabolic rate between selection lines., (© 2019 Wiley Periodicals, Inc.)

Introduction: Prader-Willi syndrome (PWS) is a complex genetic condition characterized by hyperphagia, hypotonia, low muscle mass, excess body fat, developmental delays, intellectual disability, behavioral problems, and growth hormone deficiency. This study evaluated the safety and efficacy of orally administered Diazoxide Choline Controlled-Release Tablets (DCCR) in subjects with PWS., Method: This was a single-center, Phase II study and included a 10-week Open-Label Treatment Period during which subjects were dose escalated, followed by a 4-week Double-Blind, Placebo-Controlled Treatment Period., Results: Five female and eight male overweight or obese, adolescent and adult subjects with genetically-confirmed PWS with an average age of 15.5±2.9 years were enrolled in the study. There was a statistically significant reduction in hyperphagia at the end of the Open-Label Treatment Period (-4.32, n = 11, p = 0.006). The onset of effect on hyperphagia was rapid and greater reductions in hyperphagia were seen in subjects with moderate to severe Baseline hyperphagia (-5.50, n = 6, p = 0.03), in subjects treated with the highest dose (-6.25, n = 4, p = 0.08), and in subjects with moderate to severe Baseline hyperphagia treated with the highest dose (-7.83, n = 3, p = 0.09). DCCR treatment resulted in a reduction in the number of subjects displaying aggressive behaviors (-57.1%, n = 10, p = 0.01), clinically-relevant reductions in fat mass (-1.58 kg, n = 11, p = 0.02) and increases in lean body mass (2.26 kg, n = 11, p = 0.003). There was a corresponding decrease in waist circumference, and trends for improvements in lipids and insulin resistance. The most common adverse events were peripheral edema and transient increases in glucose. Many of the adverse events were common medical complications of PWS and diazoxide., Conclusion: DCCR treatment appears to address various unmet needs associated with PWS, including hyperphagia and aggressive behaviors in this proof-of-concept study. If the results were replicated in a larger scale study, DCCR may be a preferred therapeutic option for patients with PWS., Competing Interests: The authors have read the journal’s policy and have the following conflicts: Virginia Kimonis has received support from Essentialis Therapeutics, Inc, Carlsbad, CA and Rhythm Pharmaceuticals for a clinical trial. Neil M. Cowen is affiliated with Essentialis Therapeutics, Inc, Carlsbad, CA, now Soleno Therapeutics, Redwood City, California. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

The purpose of the work is to investigate the effects of low-dose testosterone replacement therapy (TRT) and evoked resistance training (RT) on body composition and metabolic variables after spinal cord injury (SCI). Twenty-two individuals with chronic motor complete SCI (ages 18-50 years) were randomly assigned to either TRT+RT ( n  = 11) or TRT ( n  = 11) for 16 weeks following a 4 -week delayed entry period. TRT+RT men underwent twice weekly progressive RT using electrical stimulation with ankle weights. TRT was administered via testosterone patches (2-6 mg/day). Body composition was tested using anthropometrics, dual energy x-ray absorptiometry, and magnetic resonance imaging. After an overnight fast, basal metabolic rate (BMR), lipid panel, serum testosterone, adiponectin, inflammatory and anabolic biomarkers (insulin-like growth factor-1 and insulin-like growth factor-binding protein 3 [IGFBP-3]), glucose effectiveness (Sg), and insulin sensitivity (Si) were measured. Total body lean mass (LM; 2.7 kg, p  < 0.0001), whole muscle ( p  < 0.0001), and whole muscle knee extensor cross-sectional areas (CSAs; p  < 0.0001) increased in the TRT+RT group, with no changes in the TRT group. Visceral adiposity decreased ( p  = 0.049) in the TRT group, with a trend in the TRT+RT ( p  = 0.07) group. There was a trend ( p  = 0.050) of a 14-17% increase in BMR following TRT+RT. Sg showed a trend ( p  = 0.07) to improvement by 28.5-31.5% following both interventions. IGFBP-3 increased ( p  = 0.0001) while IL-6 decreased ( p  = 0.039) following both interventions, and TRT+RT suppressed adiponectin ( p  = 0.024). TRT+RT resulted in an increase in LM and whole thigh and knee extensor muscle CSAs, with an increase in BMR and suppressed adiponectin. Low-dose TRT may mediate modest effects on visceral adipose tissue, Sg, IGFBP-3, and IL-6, independent of changes in LM.

Engineered nanomaterials (ENMs) tend to precipitate in saline waters so the majority of aquatic toxicity studies have focused on freshwaters, where bioavailability is presumed to be higher. Recent studies have illustrated that some ENM formulations are bioavailable and bioactive in salt water and that their effects are more pronounced at the physiological than biochemical level. These findings raise concerns regarding the effects of ENMs on marine organisms. Therefore, our goal was to characterize the effects of polyvinylpyrolidone-functionalized silver ENMs (nAg) on aerobic performance in the killifish (Fundulus heteroclitus), a common euryhaline teleost. Fish were exposed to 80 μg L -1 of 5 nm nAg for 48 h in brackish water (12 ppt) and routine (ṀO 2min ) and maximum (ṀO 2max ) rates of oxygen consumption were quantified. Silver dissolution was minimal and nAg remained well dispersed in brackish water, with a hydrodynamic diameter of 21.0 nm, compared to 19.3 in freshwater. Both ṀO 2min and ṀO 2max were significantly lower (by 53 and 30%, respectively) in killifish exposed to nAg and a reduction in ṀO 2 variability suggested spontaneous activity was suppressed. Neither gill Na + /K + -ATPase activity, nor various other biochemical markers were affected by nAg exposure. The results illustrate that a common ENM formulation is bioactive in salt water and, as in previous studies on functionalized copper ENMs, that effects are more pronounced at the whole animal than the biochemical level., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Biomarkers are frequently used in ecotoxicology as they allow to study toxicant effects happening at low concentrations of exposure. However, most sublethal studies only evaluate cellular biomarkers which lack evident ecological relevance. We used a multibiomarker approach to estimate the toxic effects of ethoprophos, an organophosphate insecticide commonly used in banana plantations, on the tropical fish Astyanax aeneus (Characidae). We measured biomarkers at sub-individual (cellular) and individual (metabolism, behavior) levels and examined relationships among these responses. A sublethal exposure to ethoprophos caused a significant (54%) reduction of brain Cholinesterase (ChE) activity, reflecting the pesticide's high neurotoxicity. However, other biomarkers like oxidative stress, biotransformation reactions, and resting metabolic rate were not affected. Exposure to ethoprophos modified antipredator behaviors such as escape response and detection avoidance (light/dark preference): exposed fish escaped slower from a simulated attack and preferred brighter areas in a novel tank. The relationship between ChE activity and reaction time suggests that pesticide-induced ChE inhibition reduces escape ability in fish. Our results provide evidence that impacts of organophosphate pesticides on fish ecological fitness can occur even with short exposures at very low concentrations.

Leptin resistance is a hallmark of obesity with unclear etiology. Celastrol, a compound found in the roots of the Tripterygium wilfordii and known to reduce endoplasmic reticulum (ER) stress, has recently emerged as a promising candidate to treat obesity by improving leptin sensitivity. However, the underlying neural mechanisms by which celastrol reduces obesity remain unclear. Using three different mouse models of obesity-diet-induced obesity (DIO), leptin receptor (LepR)-null, and melanocortin 4 receptor (MC4R)-null mice-in this study, we show that systemic celastrol administration substantially reduces food intake and body weight in MC4R-null comparable to DIO, proving the MC4R-independent antiobesity effect of celastrol. Body weight reduction was due to decreases in both fat and lean mass, and modest but significant body weight reduction was also observed in nonobese wild-type and LepR-null mice. Unexpectedly, celastrol upregulated proinflammatory cytokines without affecting genes involved in ER stress. Importantly, celastrol steadily increased sympathetic nerve activity to the brown fat and kidney with concordant increases of resting metabolic rate and arterial pressure. Our results suggest a previously unappreciated mechanism of action of celastrol in the regulation of energy homeostasis and highlight the need for careful consideration of its development as a safe antiobesity medication., (© 2019 by the American Diabetes Association.)

Background: We investigated the effects of preoperative oral carbohydrate loading on intraoperative catabolism, nutritional parameters, and adipocytokine levels during anesthesia., Methods: Study participants were randomized to two groups who were allowed to consume either no more than 250 mL of 18% oral carbohydrate solution (Arginaid Water: AW group) or no more than 500 mL of plain water (PW group) within the 2 hours before surgery, with no intraoperative glucose administration. Percentage changes from preoperative values of resting metabolic rate (RMR) and total body water (TBW), determined by bioelectrical impedance analysis (BIA), were compared. Blood levels of serum ketone bodies, free fatty acids (FFAs), insulin, 3-methyl histidine, blood glucose, retinol binding protein, adiponectin, and leptin were measured. BIA measurement and blood sampling were performed on entry to the operating room (M1) and 2 hours after the induction of anesthesia (M2). Chi squared test, Mann-Whitney U test, and Wilcoxon's test were used for comparisons of parameters. P values less than 0.05 constituted a significant difference., Results: Seventeen patients per group (34 patients total) were enrolled. RMR and TBW values did not differ between M1 and M2 measurements. Participants in the AW group had lower blood ketone body and FFA levels and higher insulin levels at M1. However, their ketone body and FFA levels rose and insulin levels fell after 2 hours, although ketone body and FFA levels in the AW group were still lower than those in the PW group. Although retinol binding protein, adiponectin, and leptin levels were not different in terms of preoperative oral carbohydrate loading, the levels of these substances in both groups were lower after 2 hours compared with levels on operating room entry., Conclusions: Preoperative oral carbohydrate loading without intraoperative glucose administration appears to suppress catabolism for 2 hours after the start of surgery., Competing Interests: The authors have declared that no competing interests exist.

Supplementation with inulin-propionate ester (IPE), which delivers propionate to the colon, suppresses ad libitum energy intake and stimulates the release of satiety hormones acutely in humans, and prevents weight gain. In order to determine whether IPE remains effective when incorporated into food products (FP), IPE needs to be added to a widely accepted food system. A bread roll and fruit smoothie were produced. Twenty-one healthy overweight and obese humans participated. Participants attended an acclimatisation visit and a control visit where they consumed un-supplemented food products (FP). Participants then consumed supplemented-FP, containing 10 g/d inulin or IPE for six days followed by a post-supplementation visit in a randomised crossover design. On study visits, supplemented-FP were consumed for the seventh time and ad libitum energy intake was assessed 420 min later. Blood samples were collected to assess hormones and metabolites. Resting energy expenditure (REE) was measured using indirect calorimetry. Taste and appearance ratings were similar between FP. Ad libitum energy intake was significantly different between treatments, due to a decreased intake following IPE-FP. These observations were not related to changes in blood hormones and metabolites. There was an increase in REE following IPE-FP. However, this effect was lost after correcting for changes in fat free mass. Our results suggest that IPE suppresses appetite and may alter REE following its incorporation into palatable food products.

Although dietary iron is a determinant of iron status in animals, body fat mass has been reported to have an inverse association with iron status in human studies. The goal of this study was to determine the relationship between Fe homeostasis, body composition, energy expenditure and neuroendocrine regulators for severe Fe-deficiency anaemia. Forty male Wistar albino rats recently weaned were divided at random into two groups: the control group was fed the basal diet, AIN-93G diet (normal-Fe) and the anaemic group received a low-Fe diet for 40 days. Neuroendocrine parameters that regulate basal metabolism and appetite (thyroid hormones, ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon, insulin, adrenocorticotropic hormone and corticosterone), body composition, respiratory volumes, energy expenditure, haematological and biochemical were assessed. Total body fat was lower, whereas lean mass, free and total water were higher in the anemic group. O₂ consumption, CO₂ production, energy expenditure (EE) and respiratory quotient (RQ) were lower in the Fe-deficient animals. Triiodothyronine and thyroxine hormones decreased, while thyroid-stimulating hormone increased in the anemic group. Circulating levels of ghrelin were lower in the anemic group, while GIP, glucagon, insulin, corticosterone and adrenocorticotropic hormone levels were higher. Fe-deficiency impairs weight gain in the rats, with marked reductions in lean mass and body fat, indicating lower energy stores.

Objective: The role of selective β2-adrenergic stimulation in regulation of leg glucose uptake and free fatty acid (FFA) balance is inadequately explored in humans. The objective of this study was to investigate β2-adrenergic effects on net leg glucose uptake and clearance, as well as FFA balance at rest and during exercise., Design: The study was a randomized, placebo-controlled crossover trial where 10 healthy men received either infusion of β2-agonist terbutaline (0.2 to 0.4 mg) or placebo. Net leg glucose uptake and clearance and FFA balance were determined at rest and during 8 minutes of knee extensor exercise using Fick's principle. Vastus lateralis muscle biopsies were collected at rest and at cessation of exercise. The primary outcome measure was net leg glucose uptake., Results: At rest, net leg glucose uptake and clearance were 0.35 (±0.16) mmol/min and 41 (±17) mL/min (mean ± 95% CI) higher (P < 0.001) for terbutaline than placebo, corresponding to increases of 84% and 70%. During exercise, no treatment differences were observed in net leg glucose uptake, whereas clearance was 101 (±86) mL/min lower (P < 0.05) for terbutaline than placebo. At rest, terbutaline induced a net leg FFA release of 21 (±14) µmol/min, being different from placebo (P = 0.04). During exercise, net leg FFA uptake was not different between the treatments., Conclusions: These observations indicate that β2-agonist alters net leg glucose uptake and clearance, as well as FFA balance in humans, which is associated with myocellular β2-adrenergic and insulin-dependent signaling. Furthermore, the study shows that exercise confounds the β2-adrenergic effect on net leg glucose uptake and FFA balance.

Purpose: The effects of growth hormone (GH) treatment on linear growth and body composition have been studied extensively. Little is known about the GH effect on energy expenditure (EE). The aim of this study was to investigate the effects of GH treatment on EE in children, and to study whether the changes in EE can predict the height gain after 1 year., Methods: Total EE (TEE), basal metabolic rate (BMR), and physical activity level (PAL) measurements before and after 6 weeks of GH treatment were performed in 18 prepubertal children (5 girls, 13 boys) born small for gestational age (n = 14) or with growth hormone deficiency (n = 4) who were eligible for GH treatment. TEE was measured with the doubly labelled water method, BMR was measured with an open-circuit ventilated hood system, PAL was assessed using an accelerometer for movement registration and calculated (PAL = TEE/BMR), activity related EE (AEE) was calculated [AEE = (0.9 × TEE) - BMR]. Height measurements at start and after 1 year of GH treatment were analysed. This is a 1-year longitudinal intervention study, without a control group for comparison., Results: BMR and TEE increased significantly (resp. 5% and 7%). Physical activity (counts/day), PAL, and AEE did not change. 11 out of 13 patients (85%) with an increased TEE after 6 weeks of GH treatment had a good first-year growth response (∆height SDS > 0.5)., Conclusions: GH treatment showed a positive effect on EE in prepubertal children after 6 weeks. No effect on physical activity was observed. The increase in TEE appeared to be valuable for the prediction of good first-year growth responders to GH treatment.

It remains unknown how molluscs will respond to oceans which are increasingly predicted to be warmer, more acidic, and heavily polluted. Ocean acidification and trace metals will likely interact to increase the energy demands of marine organisms, especially oysters. This study tested the interactive effect of exposure to elevated pCO 2 and copper on the energetic demands of the Sydney rock oyster (Saccostrea glomerata) during reproductive conditioning and determined whether there were any positive or negative effects on their offspring. Oysters were exposed to elevated pCO 2 (1000 μatm) and elevated copper (Cu 50 μg L -1 [0.787 μM]) in an orthogonal design for eight weeks during reproductive conditioning. After eight weeks, energetic demands on oysters were measured including standard metabolic rate (SMR), nitrogen excretion, molar oxygen to nitrogen (O:N) ratio, and pH e of adult oysters as well as the size and total lipid content of their eggs. To determine egg viability, the gametes were collected and fertilised from adult oysters, the percentage of embryos that had reached the trochophore stage after 24 h was recorded. Elevated pCO 2 caused a lower extracellular pH and there was a greater O:N ratio in adult oysters exposed to copper. While the two stressors did not interact to cause significant effects on adult physiology, they did interact to reduce the size and lipid content of eggs indicating that energy demand on adult oysters was greater when both elevated pCO 2 and copper were combined. Despite the lower energy, there were no negative effects on early embryonic development. In conclusion, elevated pCO 2 can interact with metals and cause greater energetic demands on oysters; in response oysters may lower maternal investment to offspring., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Earthworms improve the soil fertility and they are also sensitive to soil contaminants. Earthworms (Eisenia fetida), standard reference species, were usually chosen to culture and handle for toxicity tests. Metabolic responses in earthworms exposed to 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209) were inhibitory and interfered with basal metabolism. In this study, 1 H-NMR based metabolomics was used to identify sensitive biomarkers and explore metabolic responses of earthworms under sub-lethal BDE-47 and BDE-209 concentrations for 14 days. The results revealed that lactate was accumulated in earthworms exposed to BDE-47 and BDE-209. Glutamate increased significantly when the concentration of BDE-47 and BDE-209 reached 10 mg/kg. The BDE-47 exposure above 50 mg/kg concentration decreased the content of fumarate significantly, which was noticed different from that of BDE-209. Whereas, the BDE-207 or BDE-209 exposure increased the protein degradation into amino acids in vivo. The increased betaine content indicated that earthworms may maintain the cell osmotic pressure and protected enzyme activity by metabolic regulation. Moreover, the BDE-47 and BDE-209 exposure at 10 mg/kg changed most of the metabolites significantly, indicating that the metabolic responses were more sensitive than growth inhibition and gene expression. The metabolomics results revealed the toxic modes of BDE-47 and BDE-209 act on the osmoregulation, energy metabolism, nerve activities, tricarboxylic acid cycle and amino acids metabolism. Furthermore, our results highlighted that the 1 H-NMR based metabolomics is a strong tool for identifying sensitive biomarkers and eco-toxicological assessment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The development of connected health devices has allowed for a more accurate assessment of a person's state under free-living conditions. In this work, we use two mobile sensing devices and investigate the correlation between individual's resting metabolic rate (RMR) and volatile organic compounds (VOCs) exposure levels. A total of 17 healthy, young, and sedentary office workers were recruited, measured for RMR with a mobile indirect calorimetry (IC) device, and compared with their corresponding predicted RMR values from the Academy of Nutrition and Dietetics' recommended epidemiological equation, the Mifflin⁻St Jeor equation (MSJE). Individual differences in the RMR values from the IC device and the epidemiological equation were found, and the subjects' RMRs were classified as normal, high, or low based on a cut-off of ±200 kcal/day difference with respect to the predicted value. To study the cause of the difference, VOCs exposure levels of each participant's daytime working environment and nighttime resting environment were assessed using a second mobile sensing device for VOCs exposure detection. The results showed that all sedentary office workers had a low VOCs exposure level (<2 ppmC), and there was no obvious correlation between VOCs exposure and the RMR difference. However, an additional participant who was a worker in an auto repair shop, showed high VOCs exposure with respect to the sedentary office worker population and a significant difference between measured and predicted RMR, with a low RMR of 500 kcal/day difference. The mobile sensing devices have been demonstrated to be suitable for the assessment of direct information of human health⁻environment interactions at free-living conditions.

A Comparison of the Direct Cerebral Vasodilating Potencies of Halothane and Isoflurane in the New Zealand White Rabbit. By Drummond JC, Todd MM, Scheller MS, and Shapiro HM. ANESTHESIOLOGY 1986; 65:462-7. Reprinted with permission.Halothane is commonly viewed as a more potent cerebral vasodilator than isoflurane. It was speculated that the lesser vasodilation caused by isoflurane might be the result of the greater reduction in cerebral metabolic rate (CMR) that it causes, and that the relative vasodilating potencies of halothane and isoflurane would be similar if the two agents were administered in a situation that precluded volatile-agent-induced depression of CMR. To test this hypothesis, cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) were measured in two groups of rabbits before and after the administration of 0.75 MAC halothane or isoflurane. One group received a background anesthetic of morphine and N2O, which resulted in an initial CMRO2 of 3.21 ± 0.17 (SEM) ml · 100 g · min; second group received a background anesthetic of high-dose pentobarbital, which resulted in an initial CMRO2 of 1.76 ± 0.16 ml · 100 g · min. In rabbits receiving a background of morphine sulfate/N2O, halothane resulted in a significantly greater CBF (65 ± 10 ml · 100 g · min) than did isoflurane (40 ± 5 ml · 100 g · min). Both agents caused a reduction in CMRO2, but CMRO2 was significantly less during isoflurane administration. By contrast, with a background of pentobarbital anesthesia, CBF increased by significant and similar amounts with both halothane and isoflurane. With halothane, CBF increased from 22 ± 2 ml · 100 g · min in the control stage to 39 ± 3, and with isoflurane from 24 ± to 38 ± 2 ml · 100 g · min. CMRO2 was not depressed further by either halothane or isoflurane. These results suggest that the relative effects of halothane and isoflurane on CBF are dependent on the CMR present prior to their administration. When the preexistent CMR is not markedly depressed, isoflurane decreases CMR and causes less cerebral vasodilation than does halothane. When initial CMR is depressed, halothane and isoflurane have similar vasodilating potencies.

Aims: When treated with basal insulin peglispro (BIL), patients with type 1 diabetes mellitus (T1DM) exhibit weight loss and lower prandial insulin requirements versus insulin glargine (GL), while total insulin requirements remain similar. One possible explanation is enhanced lipid oxidation and improved ability to switch between glucose and lipid metabolism with BIL. This study compared the effects of BIL and GL on glucose and lipid metabolism in subjects with T1DM., Materials and Methods: Fifteen subjects with T1DM were enrolled into this open-label, randomised, crossover study, and received once-daily stable, individualised, subcutaneous doses of BIL and GL for 4 weeks each. Respiratory quotient (RQ) was measured using whole-room calorimetry, and energy expenditure (EE) and concentrations of ketone bodies (3-hydroxybutyrate) and acylcarnitines were assessed., Results: Mean sleep RQ was lower during the BIL (0.822) than the GL (0.846) treatment period, indicating greater lipid metabolism during the post-absorptive period with BIL. Increases in carbohydrate oxidation following breakfast were greater during BIL than GL treatment (mean change in RQ following breakfast 0.111 for BIL, 0.063 for GL). Furthermore, BIL treatment increased total daily EE versus GL (2215.9 kcal/d for BIL, 2135.5 kcal/d for GL). Concentrations of ketone bodies and acylcarnitines appeared to be higher following BIL than GL treatment., Conclusions: BIL increased sleeping fat oxidation, EE, ketone bodies, acylcarnitines and post-prandial glucose metabolism when switching from conventional insulin, thus, restoring metabolic flexibility and increasing thermogenesis. These changes may explain the previously observed weight loss with BIL versus GL., (© 2018 John Wiley & Sons Ltd.)

Although capsaicin has been reported to reduce energy intake and increase energy expenditure in an adult (normal weight or overweight) population, thus resulting in a net negative energy balance and weight loss, these beneficial effects have not been investigated in young obese subjects. We hypothesize that capsaicin acutely administered in young obese subjects exerts the same effects on energy balance and that these effects are mediated by changes in gastrointestinal peptides regulating appetite. Thus, the aim of the present study was to evaluate the acute effects of capsaicin (2 mg) or placebo on energy intake, hunger, and satiety in obese adolescents and young adults (female-male ratio: 4:6, age: 21.0 ± 5.8 years; body mass index: 41.5 ± 4.3 kg/m 2 ) provided an ad libitum dinner. Furthermore, circulating levels of some orexigenic (ghrelin) and anorexigenic (glucagon-like peptide 1 and peptide YY) peptides were measured after a meal completely consumed (lunch), together with the evaluation of hunger and satiety and assessment of resting energy expenditure (REE) through indirect computerized calorimetry. When compared to placebo, capsaicin did not significantly change either energy intake or hunger/satiety 6 hours after its administration (dinner). No differences in circulating levels of ghrelin, glucagon-like peptide 1, and peptide YY and in hunger/satiety were found in the 3 hours immediately after food ingestion among obese subjects treated with capsaicin or placebo (lunch). By contrast, the meal significantly increased REE in the capsaicin- but not placebo-treated group (capsaicin: from 1957.2 ± 455.1 kcal/d up to 2342.3 ± 562.1 kcal/d, P < .05; placebo: from 2060.1 ± 483.4 kcal/d up to 2296.0 ± 484.5 kcal/d). The pre-post meal difference in REE after capsaicin administration was significantly higher than that observed after placebo (385.1 ± 164.4 kcal/d vs 235.9 ± 166.1 kcal/d, P < .05). In conclusion, although capsaicin does not exert hypophagic effects, these preliminary data demonstrate its ability as a metabolic activator in young obese subjects., (Copyright © 2018. Published by Elsevier Inc.)

Short-chain fatty acids (SCFAs), produced from fermentation of dietary fibre by the gut microbiota, have been suggested to modulate energy metabolism. Previous work using rodent models has demonstrated that oral supplementation of the SCFA propionate raises resting energy expenditure (REE) by promoting lipid oxidation. The objective of the present study was to investigate the effects of oral sodium propionate on REE and substrate metabolism in humans. Eighteen healthy volunteers (9 women and 9 men; age 25 ± 1 years; body mass index 24.1 ± 1.2 kg/m 2 ) completed 2 study visits following an overnight fast. Tablets containing a total of 6845 mg sodium propionate or 4164 mg sodium chloride were provided over the 180-minute study period in random order. REE and substrate oxidation were assessed by indirect calorimetry. Oral sodium propionate administration increased REE (0.045 ± 0.020 kcal/min; P = .036); this was accompanied by elevated rates of whole-body lipid oxidation (0.012 ± 0.006 g/min; P = .048) and was independent of changes in glucose and insulin concentrations. Future studies are warranted to determine whether the acute effects of oral sodium propionate on REE translate into positive improvements in long-term energy balance in humans., (© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Dichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are amongst most prevalent pesticides in the environment. Although their toxicity has been extensively studied, molecular mechanisms and metabolic effects remain unclear, including in liver where their detoxification occurs. Here, we used metabolomics, coupled to RT-qPCR analysis, to examine effects of DDT and PMT on hepatocytes cultivated in biochips. At 150 μM, DDT caused cell death, cytochrome P450 induction and modulation of estrogen metabolism. Metabolomics analysis showed an increase in some lipids and sugars after 6 h, and a decrease in fatty acids (tetradecanoate, octanoate and linoleate) after 24 h exposure. We also found a change in expression associated with genes involved in hepatic estrogen, lipid, and sugar metabolism. PMT at 150 μM perturbed lipid/sugar homeostasis and estrogen signaling pathway, between 2 and 6 h. After 24 h, lipids and sugars were found to decrease, suggesting continuous energy demand to detoxify PMT. Finally, at 15 μM, DDT and PMT appeared to have a small effect on metabolism and were detoxified after 24 h. Our results show a time-dependent perturbation of sugar/lipid homeostasis by DDT and PMT at 150 μM. Furthermore, DDT at high dose led to cell death, inflammatory response and oxidative stress., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Crotamine, originally isolated from rattlesnake venom, has been extensively studied due to its pleiotropic biological properties, and special attention has been paid to its antitumor activity. However, long-term treatment with crotamine was accompanied by a reduction in animal body weight gain and by increases in glucose tolerance. As cancer is commonly associated with cachexia, to preclude the possible cancer cachexia-like effect of crotamine, herein this polypeptide was administered in healthy wild-type C57/BL6 mice by the oral route daily, for 21 days. Reduced body weight gain, in addition to decreased white adipose tissue (WAT) and increased brown adipose tissue (BAT) mass were observed in healthy animals in the absence of tumor. In addition, we observed improved glucose tolerance and increased insulin sensitivity, accompanied by a reduction of plasma lipid levels and decreased levels of biomarkers of liver damage and kidney disfunctions. Importantly, long-term treatment with crotamine increased the basal metabolic rate in vivo, which was consistent with the increased expression of thermogenic markers in BAT and WAT. Interestingly, cultured brown adipocyte cells induced to differentiation in the presence of crotamine also showed increases in some of these markers and in lipid droplets number and size, indicating increased brown adipocyte maturation.

Mammals usually possess a majority of medium-wavelength sensitive (M-) and a minority of short-wavelength sensitive (S-) opsins in the retina, enabling dichromatic vision. Unexpectedly, subterranean rodents from the genus Fukomys exhibit an S-opsin majority, which is exceptional among mammals, albeit with no apparent adaptive value. Because thyroid hormones (THs) are pivotal for M-opsin expression and metabolic rate regulation, we have, for the first time, manipulated TH levels in the Ansell's mole-rat (Fukomys anselli) using osmotic pumps. In Ansell's mole-rats, the TH thyroxine (T4) is naturally low, likely as an adaptation to the harsh subterranean ecological conditions by keeping resting metabolic rate (RMR) low. We measured gene expression levels in the eye, RMR, and body mass (BM) in TH-treated animals. T4 treatment increased both, S- and M-opsin expression, albeit M-opsin expression at a higher degree. However, this plasticity was only given in animals up to approximately 2.5 years. Mass-specific RMR was not affected following T4 treatment, although BM decreased. Furthermore, the T4 inactivation rate is naturally higher in F. anselli compared to laboratory rodents. This is the first experimental evidence that the S-opsin majority in Ansell's mole-rats is a side effect of low T4, which is downregulated to keep RMR low.

Recent studies have shown that dietary intake and genetic variants play a decisive role in the risk of obesity. Therefore, this study was designed to examine the interaction between dietary fat and PPARGC1A polymorphisms on the level of resting metabolic rate (RMR). We enrolled 288 Iranian overweight and obese women in this cross-sectional study. We sequenced the 648 b.p. DNA in Exon 8 of PPARGC1A gene. We analyzed the two single-nucleotide polymorphisms, namely rs11290186 and rs2970847, in this region. All participants were assessed for RMR, dietary intake, and body composition. This study demonstrated that total cholesterol and insulin levels were positively associated with T allele carriers of rs2970847. Moreover, the A-deletion allele carrier of the rs11290186 genotype had higher triacylglycerol and insulin concentrations. The current study revealed that, after adjustment for energy intake, the AA genotype of PPARGC1A (rs11290186) had a direct association with polyunsaturated fatty acids and linoleic acid intakes. Another important finding in our study was that there was an interaction seen between fat and saturated fatty acids intake with the PPARGC1A genotypes. Women with fat intakes of more than 30% of calorie intake per day and the A-deletion genotype had a lower RMR and RMR/fat free mass (FFM). It seems that the PPARGC1A polymorphisms lead to the downregulation of insulin signaling and subsequently insulin resistance. In addition, the interactions between the PPARGC1A polymorphisms (rs11290186) and the level of dietary fat intake probably can have an effect on RMR and RMR/FFM in obese women., (© 2018 AOCS.)