High energy expenditure is not protective against increased adiposity in children.
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ABSTRACT:
SUBMITTER: Zinkel SR
PROVIDER: S-EPMC4993690 | biostudies-literature | 2016 Dec
REPOSITORIES: biostudies-literature
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Project description:Ten-eleven translocation (TET) proteins oxidize 5-methylcytosine in DNA to 5- hydroxymethylcytosine and further oxidized derivatives. Here we show that TET proteins are key epigenetic suppressors of adipocyte thermogenesis and energy expenditure in both white and brown adipose tissues in vivo. Tet expression in adipocytes decreases upon cold or adrenergic stimulation but increases following high-fat diet (HFD) consumption. Mice with triple deletion of all three Tet genes in adipocytes have higher energy expenditure due to enhanced fat browning and thermogenesis. They also show significantly enhanced lipolysis because of elevated expression of Adrb3 and key lipases including Atgl and Hsl. Consequently, the knockout mice display improved cold tolerance and are substantially resistant to obesity, inflammation, and associated metabolic complications including insulin resistance. Mechanistically, TET deficiency substantially prevents the HFD-induced transcriptional alterations in adipose tissues. TET proteins recruit histone deacetylases (HDACs) to the key thermogenic gene loci including Adrb3, Ppargc1a, and Ucp1, leading to transcriptional repression through histone deacetylation. Thus, the TET-HDAC axis may be therapeutically targeted to treat obesity and related metabolic diseases.
2021-11-01 | GSE178762 | GEO
Project description:Background/objectivesEpidemics of obesity and diabetes are escalating. High-calorie/high-fat food is a major cause for these global health issues, but molecular mechanisms underlying high-fat, diet-induced obesity are still not well understood. The aryl hydrocarbon receptor (AhR), a transcription factor that acts as a xenobiotic sensor, mediates environmental toxicant-induced obesity, insulin resistance and development of diabetes. AhR also influences lipid metabolism and diet-induced obesity. The effects of AhR deficiency on diet-induced obesity, hepatic steatosis and insulin resistance were examined.MethodsMale wild-type (WT), AhR null (AhR(-/-)) and AhR heterozygote (AhR(+/-)) mice were fed a normal chow diet (NCD, 10% kcal from fat) or a high-fat diet (HFD, 60% kcal from fat) for up to 14 weeks. Adiposity, adipose and liver morphology, insulin signaling, metabolic parameters and gene profiles were assessed.ResultsAhR deficiency protected against HFD-induced obesity, hepatic steatosis, insulin resistance and inflammation. Moreover, AhR deficiency preserved insulin signaling in major metabolic tissues. These protective effects result from a higher energy expenditure in AhR-deficient mice compared with WT. Levels of transcript for both the thermogenic gene, uncoupling protein 1 (Ucp1), in brown adipose tissue and mitochondrial β-oxidation genes in muscle were significantly higher in AhR(-/-) and AhR(+/-) mice compared with WT.ConclusionsThis work documents a physiologically relevant function for AhR in regulation of body weight, hepatic fat deposition, insulin sensitivity and energy expenditure under HFD exposure, suggesting that AhR signaling may be developed as a potential therapeutic target for treatment of obesity and metabolic disorders.
| S-EPMC4526411 | biostudies-literature
Project description:The role of the tumor suppressor retinoblastoma protein (pRb) has been firmly established in the control of cell cycle, apoptosis, and differentiation. Recently, it was demonstrated that lack of pRb promotes a switch from white to brown adipocyte differentiation in vitro. We used the Cre-Lox system to specifically inactivate pRb in adult adipose tissue. Under a high-fat diet, pRb-deficient (pRb(ad-/-)) mice failed to gain weight because of increased energy expenditure. This protection against weight gain was caused by the activation of mitochondrial activity in white and brown fat as evidenced by histologic, electron microscopic, and gene expression studies. Moreover, pRb(-/-) mouse embryonic fibroblasts displayed higher proliferation and apoptosis rates than pRb(+/+) mouse embryonic fibroblasts, which could contribute to the altered white adipose tissue morphology. Taken together, our data support a direct role of pRb in adipocyte cell fate determination in vivo and suggest that pRb could serve as a potential therapeutic target to trigger mitochondrial activation in white adipose tissue and brown adipose tissue, favoring an increase in energy expenditure and subsequent weight loss.
| S-EPMC1965576 | biostudies-literature
Project description:Zebrafish are an important model organism with inherent advantages that have the potential to make zebrafish a widely applied model for the study of energy homeostasis and obesity. The small size of zebrafish allows for assays on embryos to be conducted in a 96- or 384-well plate format, Morpholino and CRISPR based technologies promote ease of genetic manipulation, and drug treatment by bath application is viable. Moreover, zebrafish are ideal for forward genetic screens allowing for novel gene discovery. Given the relative novelty of zebrafish as a model for obesity, it is necessary to develop tools that fully exploit these benefits. Herein, we describe a method to measure energy expenditure in thousands of embryonic zebrafish simultaneously. We have developed a whole animal microplate platform in which we use 96-well plates to isolate individual fish and we assess cumulative NADH2 production using the commercially available cell culture viability reagent alamarBlue. In poikilotherms the relationship between NADH2 production and energy expenditure is tightly linked. This energy expenditure assay creates the potential to rapidly screen pharmacological or genetic manipulations that directly alter energy expenditure or alter the response to an applied drug (e.g. insulin sensitizers).
| S-EPMC4781700 | biostudies-other
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-04-20 | GSE230208 | GEO
Project description:BackgroundDespite growing scientific interest in the benefits of breaking up sedentary time with intermittent standing or walking, few studies have investigated the energy cost of posture transitions. This study aimed to determine whether posture transitions are associated with increased energy expenditure in preschool children.MethodsForty children (mean age 5.3 ± 1.0y) completed a ~150-min room calorimeter protocol involving sedentary, light, and moderate- to vigorous-intensity activities. This study utilised data from ~65-min of the protocol, during which children were undertaking sedentary behaviours (TV viewing, drawing/colouring in, and playing with toys on the floor). Posture was coded as sit/lie, stand, walk, or other using direct observation; posture transitions were classified as sit/lie to stand/walk, sit/lie to other, stand/walk to other, or vice versa. Energy expenditure was calculated using the Weir equation and used to calculate individualised MET and activity energy expenditure (AEE) values. Spearman's rank correlations were used to compare the number of posture transitions, in the individual activities separately and combined, with corresponding MET and AEE values. Participants were divided into tertiles based on the number of posture transitions; MET and AEE values of children in the lowest and highest tertiles of posture transitions were compared using unpaired t-tests. Effect sizes (Cohen's d) were calculated.ResultsThere was a positive correlation between the total number of posture transitions and average METs (rs = 0.42, p = 0.02) and AEE (rs = 0.43, p = 0.02). MET differences between the lowest and highest tertiles of posture transitions resulted in a small effect size for playing with toys (d = 0.27), and moderate effect sizes for TV viewing, drawing and all three activities combined (d = 0.61, 0.50 and 0.64 respectively). Similar results were found for AEE.ConclusionsResults from this study showed that variation in posture transitions may be associated with variation in energy expenditure in preschool children. The findings suggest that the concept that variation in posture transitions may have meaningful biological or health effects in early childhood is worth investigating further.
| S-EPMC6464188 | biostudies-literature
Project description:ContextPatients with pseudohypoparathyroidism type 1a (PHP-1a) develop early-onset obesity. The abnormality in energy expenditure and/or energy intake responsible for this weight gain is unknown.ObjectiveThe aim of this study was to evaluate energy expenditure in children with PHP-1a compared with obese controls.PatientsWe studied 6 obese females with PHP-1a and 17 obese female controls. Patients were recruited from a single academic center.MeasurementsResting energy expenditure (REE) and thermogenic effect of a high fat meal were measured using whole room indirect calorimetry. Body composition was assessed using whole body dual energy x-ray absorptiometry. Fasting glucose, insulin, and hemoglobin A1C were measured.ResultsChildren with PHP-1a had decreased REE compared with obese controls (P<0.01). After adjustment for fat-free mass, the PHP-1a group's REE was 346.4 kcals day(-1) less than obese controls (95% CI (-585.5--106.9), P<0.01). The thermogenic effect of food (TEF), expressed as percent increase in postprandial energy expenditure over REE, was lower in PHP-1a patients than obese controls, but did not reach statistical significance (absolute reduction of 5.9%, 95% CI (-12.2-0.3%), P=0.06).ConclusionsOur data indicate that children with PHP-1a have decreased REE compared with the obese controls, and that may contribute to the development of obesity in these children. These patients may also have abnormal diet-induced thermogenesis in response to a high-fat meal. Understanding the causes of obesity in PHP-1a may allow for targeted nutritional or pharmacologic treatments in the future.
| S-EPMC3610772 | biostudies-literature
Project description:ObjectiveThis study assessed longitudinal changes in body composition, fat distribution and energy balance in perimenopausal women. We hypothesized that total fat and abdominal body fat would increase at menopause due to decreased energy expenditure (EE) and declining estrogen, respectively.DesignObservational, longitudinal study with annual measurements for 4 years.SubjectsHealthy women (103 Caucasian; 53 African-American), initially premenopausal. During follow-up, lack of menstruation for 1 year and follicle-stimulating hormone >30 mIU ml(-1) defined a subject as postmenopausal.MeasurementsFat and lean mass (dual-energy X-ray absorptiometry), visceral (VAT) and subcutaneous abdominal fat (SAT) (computed tomography), dietary intake (4-day food record), serum sex hormones and physical activity (tri-axial accelerometry). Twenty-four hour EE was measured by whole-room calorimeter in a subset of 34 women at baseline and at year 4.ResultsBody fat and weight increased significantly over time only in those women who became postmenopausal by year 4 (n=51). All women gained SAT over time; however, only those who became postmenopausal had a significant increase in VAT. The postmenopausal group also exhibited a significant decrease in serum estradiol. Physical activity decreased significantly 2 years before menopause and remained low. Dietary energy, protein, carbohydrate and fiber intake were significantly higher 3-4 years before the onset of menopause compared with menopause onset. Twenty-four hour EE and sleeping EE decreased significantly with age; however, the decrease in sleeping EE was 1.5-fold greater in women who became postmenopausal compared with premenopausal controls (-7.9 vs -5.3%). Fat oxidation decreased by 32% in women who became postmenopausal (P<0.05), but did not change in those who remained premenopausal.ConclusionMiddle-aged women gained SAT with age, whereas menopause per se was associated with an increase in total body fat and VAT. Menopause onset is associated with decreased EE and fat oxidation that can predispose to obesity if lifestyle changes are not made.
| S-EPMC2748330 | biostudies-literature
Project description:Children undergoing hematopoietic SCT (HSCT) typically receive parenteral nutrition (PN) due to gastrointestinal toxicities. Accurate determination of resting energy expenditure (REE) may facilitate optimal energy provision and help avoid unintended overfeeding or underfeeding. A multicenter, prospective cohort study of children undergoing allogeneic HSCT was performed, in which REE was measured by indirect calorimetry at baseline and twice weekly until 30 days after transplantation. Change in percent predicted REE over time from admission was analyzed using repeated measures regression analysis. In all, 26 children (14 females) with a mean (s.d.) age of 14.9 (4.2) years who underwent an HLA-matched sibling or unrelated donor transplantation were enrolled. Mean (s.d.) percent predicted REE at baseline was 92.4 (15.2). Baseline REE was highly correlated with lean body mass measured by dual energy X-ray absorptiometry (r=0.78, P<0.0001). REE decreased significantly over time, following a quadratic curve to a nadir of 79% predicted at 14 days post transplantation (P<0.001) and returned to near baseline by day 30. Children undergoing HSCT exhibit a significant reduction in REE in the early weeks after transplantation, a phenomenon that places them at risk for overfeeding. Serial measurements of REE or reductions in energy intake should be considered when PN is the primary mode of nutrition.
| S-EPMC3366174 | biostudies-literature
Project description:ObjectiveChildren with suprasellar brain damage are at risk of hypothalamic dysfunction (HD). HD may lead to decreased resting energy expenditure (REE). Decreased REE, however, is not present in all children with HD. Our aim was to assess which children suspect for HD have low REE, and its association with clinical severity of HD or radiological hypothalamic damage.Patients and methodsA retrospective cohort study was performed. Measured REE (mREE) of children at risk of HD was compared to predicted REE (pREE). Low REE was defined as mREE <90% of predicted. The mREE/pREE quotient was associated to a clinical score for HD symptoms and to radiological hypothalamic damage.ResultsIn total, 67 children at risk of HD (96% brain tumor diagnosis) with a mean BMI SDS of +2.3 ± 1.0 were included. Of these, 45 (67.2%) had low mREE. Children with severe HD had a significant lower mean mREE/pREE quotient compared to children with no, mild, or moderate HD. Mean mREE/pREE quotient of children with posterior hypothalamic damage was significantly lower compared to children with no or anterior damage. Tumor progression or tumor recurrence, severe clinical HD, and panhypopituitarism with diabetes insipidus (DI) were significant risk factors for reduced REE.ConclusionREE may be lowered in children with hypothalamic damage and is associated to the degree of clinical HD. REE is, however, not lowered in all children suspect for HD. For children with mild or moderate clinical HD symptoms, REE measurements may be useful to distinguish between those who may benefit from obesity treatment that increases REE from those who would be better helped using other obesity interventions.
| S-EPMC9346331 | biostudies-literature