Changes In Energy Expenditure Research Articles

BGP-15 Protects against Oxaliplatin-Induced Skeletal Myopathy and Mitochondrial Reactive Oxygen Species Production in Mice.

Chemotherapy is a leading intervention against cancer. Albeit highly effective, chemotherapy has a multitude of deleterious side-effects including skeletal muscle wasting and fatigue, which considerably reduces patient quality of life and survivability. As such, a defense against chemotherapy-induced skeletal muscle dysfunction is required. Here we investigate the effects of oxaliplatin (OXA) treatment in mice on the skeletal muscle and mitochondria, and the capacity for the Poly ADP-ribose polymerase (PARP) inhibitor, BGP-15, to ameliorate any pathological side-effects induced by OXA. To do so, we investigated the effects of 2 weeks of OXA (3 mg/kg) treatment with and without BGP-15 (15 mg/kg). OXA induced a 15% (p < 0.05) reduction in lean tissue mass without significant changes in food consumption or energy expenditure. OXA treatment also altered the muscle architecture, increasing collagen deposition, neutral lipid and Ca2+ accumulation; all of which were ameliorated with BGP-15 adjunct therapy. Here, we are the first to show that OXA penetrates the mitochondria, and, as a possible consequence of this, increases mtROS production. These data correspond with reduced diameter of isolated FDB fibers and shift in the fiber size distribution frequency of TA to the left. There was a tendency for reduction in intramuscular protein content, albeit apparently not via Murf1 (atrophy)- or p62 (autophagy)- dependent pathways. BGP-15 adjunct therapy protected against increased ROS production and improved mitochondrial viability 4-fold and preserved fiber diameter and number. Our study highlights BGP-15 as a potential adjunct therapy to address chemotherapy-induced skeletal muscle and mitochondrial pathology.

Adipocyte arrestin domain-containing 3 protein (Arrdc3) regulates uncoupling protein 1 (Ucp1) expression in white adipose independently of canonical changes in β-adrenergic receptor signaling.

Adaptive thermogenesis and cold-induced activation of uncoupling protein 1 (Ucp1) in brown adipose tissue in rodents is well-described and attributed to sympathetic activation of β-adrenergic signaling. The arrestin domain containing protein Arrdc3 is a regulator of obesity in mice and also appears linked to obesity in humans. We generated a mouse with conditional deletion of Arrdc3, and here we present evidence that genetic ablation of Arrdc3 specifically in adipocytes results in increased Ucp1 expression in subcutaneous and parametrial adipose tissue. Although this increase in expression did not correspond with significant changes in body weight or energy expenditure, adipocyte-specific Arrdc3-null mice had improved glucose tolerance. It was previously hypothesized that Arrdc3 ablation leads to increased β-adrenergic receptor sensitivity; however, in vitro experiments show that Arrdc3-null adipocytes responded to β-adrenergic receptor agonist with decreased Ucp1 levels. Additionally, canonical β-adrenergic receptor signaling was not different in Arrdc3-null adipocytes. These data reveal a role for Arrdc3 in the regulation of Ucp1 expression in adipocytes. However, this adipocyte effect is insufficient to generate the obesity-resistant phenotype of mice with ubiquitous deletion of Arrdc3, indicating a likely role for Arrdc3 in cells other than adipocytes.

Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice

Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors – as reported to elicit a modulatory effect with acute administration. This leads to two alternative interpretations regarding long-term insulin IND in mice: 1) It causes an initial stage of insulin resistance to dampen the behaviors that would normally be modulated under acute insulin IND, but ability to clear a glucose challenge is still retained, or 2) There is a lack of behavioral modulation at high concentration of insulin attributed to the twice daily intervals of hyperinsulinemia caused by insulin IND administration without any insulin resistance, per se.

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain.

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well as in the adult.

Central Nervous Insulin Administration before Nocturnal Sleep Decreases Breakfast Intake in Healthy Young and Elderly Subjects.

Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning. Healthy participants who were either young (16 men and 16 women; mean age ± SEM, 23.68 ± 0.40 years, mean BMI ± SEM, 22.83 ± 0.33 kg/m2) or elderly (10 men, 9 women; 70.79 ± 0.81 years, 25.27 ± 0.60 kg/m2) were intranasally administered intranasal insulin (160 IU) or placebo before a night of regular sleep that was polysomnographically recorded. Blood was repeatedly sampled for the determination of circulating glucose, insulin, leptin and total ghrelin. In the morning, energy expenditure was assessed via indirect calorimetry and subjects were offered a large standardized breakfast buffet from which they could eat ad libitum. Insulin compared to placebo reduced breakfast size by around 110 kcal (1,054.43 ± 50.91 vs. 1,162.36 ± 64.69 kcal, p = 0.0095), in particular decreasing carbohydrate intake (502.70 ± 25.97 vs. 589.82 ± 35.03 kcal, p = 0.0080). This effect was not dependent on sex or age (all p > 0.11). Sleep architecture, blood glucose and hormonal parameters as well as energy expenditure were not or only marginally affected. Results show that intranasal insulin administered to healthy young and elderly humans before sleep exerts a delayed inhibitory effect on energy intake that is not compensated for by changes in energy expenditure. While the exact underlying mechanisms cannot be derived from our data, findings indicate a long-lasting catabolic effect of central nervous insulin delivery that extends across sleep and might be of particular relevance for potential therapeutic applications.

Post-traumatic changes in energy expenditure and body composition in patients with acute spinal cord injury.

Prospective cohort study. To investigate the changes in resting energy expenditure and body composition over time in a cohort of patients with spinal cord injury during acute treatment, rehabilitation, and 2 years after the end of rehabilitation. Adult patients admitted for acute treatment and rehabilitation after traumatic spinal cord injury were recruited. Measurements of resting energy expenditure and body composition were scheduled at 2, 6, 10 and 14 weeks after spinal cord injury, at the end of rehabilitation, and 2 years later. Patients' mean age was 38.8 years (standard deviation 14.0). Resting energy expenditure began to decrease up to the 10-week measurement (p = 0.02) and further decreased after the 130-week measurement (p< 0.001). Body weight was already decreased after the 6-week measurement (p< 0.01) and increased after the end of rehabilitation (p = 0.009). Percentage body fat mass showed similar changes. After an initial decrease in resting energy expenditure, body weight and percentage of body fat, these values levelled off during the rehabilitation period. After the end of the rehabilitation period, body weight and body fat mass increased again to the baseline levels, whereas resting energy expenditure decreased further. These results suggest that rehabilitation programmes should focus on adapting to these foreseeable changes.

Motor functions assessment method based on energy changes in gait cycle.

The aim of the research was to determine the energy changes during the gait cycle for a group of healthy children and a group of patients with cerebral palsy, and to compare the value of energy expenditure (EE) with the determined values of the Gillette Gait Index (GGI) and the Gait Deviation Index (GDI). The study group consisted of 56 children with regular gait and 56 patients with diagnosed cerebral palsy (CP). The gait kinematics was determined by BTS Smart System. Based on the identified position of the body mass, the following parameters were determined: the potential energy, kinetic energy, and total energy. The values were standardized to 100% of the gait cycle. The values of the Gillette Gait Index (GGI) and the Gait Deviation Index (GDI) were calculated using the authors' own software. Values of potential, kinematic and mechanical energy changes and mean values of total energy (energy expenditure - EE) were calculated for a reference group and for patients with CP. The obtained results were standardized in relation to the body mass and stride length. Furthermore, the values of the Gillette Gait Index (GGI) and the Gait Deviation Index (GDI) were calculated. Statistical analysis of the obtained results was performed. The Spearman rank correlation coefficient was defined between the calculated GGI and GDI values and energy expenditure EE. Values of energy expenditure changes can be used as an objective comparative tool for gait results concerning children with various neurological and orthopaedic dysfunctions.

Compensatory changes in energy balance during dapagliflozin treatment in type 2 diabetes mellitus: a randomised double-blind, placebo-controlled, cross-over trial (ENERGIZE)—study protocol

IntroductionSodium glucose cotransporter 2 (SGLT2) inhibitors are effective blood-glucose-lowering medications with beneficial effects on body weight in patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is less...

Prepregnancy body mass index influences lipid oxidation rate during pregnancy.

The influence of maternal body mass index (BMI) on respiratory quotient during pregnancy is not clear. We aim to evaluate longitudinal changes in energy expenditure, respiratory quotient, and substrate oxidation rates in normal and overweight women with uncomplicated pregnancies. We hypothesized that the threshold period in switching from a predominantly carbohydrate to a predominantly lipid metabolism may be different in normal and overweight women. Forty healthy pregnant women were recruited for a prospective cohort study. They were divided into two groups, normal and overweight (BMI <25 kg/m2 or ≥25 kg/m2 ). Comparisons of indirect calorimetry data were performed monthly throughout pregnancy. The relationships between energy and substrate metabolism variables and maternal BMI were also analyzed. There was a significant increase in oxygen consumption (Vo2 ), carbon dioxide production (Vco2 ) and resting energy expenditure during pregnancy in both normal and overweight women. In the normal weight group, respiratory quotient decreased during the second trimester and increased in the last trimester. Respiratory quotient was lower in the overweight group in the second trimester and decreased in the last trimester; between-group differences being significant at 20 and 36 weeks (0.85 ± 0.06 vs. 0.81 ± 0.01, p = 0.009; 0.87 ± 0.05 vs. 0.80 ± 0.03, p = 0.01, respectively). Lipid oxidation was significantly higher in overweight women at both 20 and 36 weeks (36.8 ± 19.7% vs. 55.2 ± 5.6%, p = 0.003 and 33.6 ± 18.2% vs. 59.6 ± 12.7%, p = 0.007, for normal and overweight group, respectively). Prepregnancy maternal BMI influences lipid oxidation rate and respiratory quotient during pregnancy.

Starvation Resulting From Inadequate Dietary Planning for a 50-Day Rowing Expedition.

To use the doubly labeled water (DLW) technique to calculate the total energy expenditure (TEE) and body-composition changes of two 28-y-old healthy male athletes during a 50-d continuous and unsupported row around Great Britain. A measured dose of DLW was taken at the start of 2 separate study periods (days 5-19 and 34-48) followed by sequential urine collection, which was analyzed on return to land. Mean TEE was 15.3 MJ/d: athlete 1, 16.4 MJ/d; athlete 2, 14.9 MJ/d. Athlete 1 lost 11.2 kg and athlete 2 lost 14.9 kg of body mass during the row. Average energy provision was 19.1 MJ per 24-h ration pack. These results highlight the difficulty of maintaining energy balance during expedition rowing. A starvation state was observed despite dietary provision in excess of estimated energy expenditure, indicating that nutritional strategy rather than caloric availability was at fault. The authors recommend that future expeditions prioritize thorough testing and the individualization of rations to ensure that they are both palatable and practical during the weeks to months at sea.

Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats.

Neutering is a significant risk factor for obesity in cats. The mechanisms that promote neuter-associated weight gain are not well understood but following neutering, acute changes in energy expenditure and energy consumption have been observed. Metabolic profiling (GC-MS and UHPLC-MS-MS) was used in a longitudinal study to identify changes associated with age, sexual development and neutering in male cats fed a nutritionally-complete dry diet to maintain an ideal body condition score. At eight time points, between 19 and 52 weeks of age, fasted blood samples were taken from kittens neutered at either 19 weeks of age (Early Neuter (EN), n = 8) or at 31 weeks of age (Conventional Neuter (CN), n = 7). Univariate and multivariate analyses were used to compare plasma metabolites (n = 370) from EN and CN cats. Age was the primary driver of variance in the plasma metabolome, including a developmental change independent of neuter group between 19 and 21 weeks in lysolipids and fatty acid amides. Changes associated with sexual development and its subsequent loss were also observed, with differences at some time points observed between EN and CN cats for 45 metabolites (FDR p<0.05). Pathway Enrichment Analysis also identified significant effects in 20 pathways, dominated by amino acid, sterol and fatty acid metabolism. Most changes were interpretable within the context of male sexual development, and changed following neutering in the CN group. Felinine metabolism in CN cats was the most significantly altered pathway, increasing during sexual development and decreasing acutely following neutering. Felinine is a testosterone-regulated, felid-specific glutathione derivative secreted in urine. Alterations in tryptophan, histidine and tocopherol metabolism observed in peripubertal cats may be to support physiological functions of glutathione following diversion of S-amino acids for urinary felinine secretion.

Effect of the menopausal transition and physical activity energy expenditure on inflammatory markers: a MONET group study.

Menopausal transition is usually associated with changes in body composition and a decrease in physical activity energy expenditure. Adipose tissue, especially visceral fat, is an important source of inflammatory markers, which contributes to the development of a proinflammatory state. Conversely, high levels of physical activity and exercise have an anti-inflammatory effect. This study aimed to investigate the impact of menopausal transition and physical activity on inflammatory makers. One hundred two healthy premenopausal women participated in a 5-year longitudinal study. The present secondary analyses were performed on 58 participants with a full set of data (age: 49.6 ± 1.7 y; body mass index: 23.3 ± 2.4 kg/m). Measures included body composition, waist circumference, fasting glucose and insulin levels, insulin sensitivity, plasma lipid levels, cardiorespiratory fitness, physical activity energy expenditure, and inflammatory markers. Repeated measure analyses revealed, after the 5-year follow-up, significant increases in ferritin, interleukin-8 (IL-8), and soluble tumor necrosis factor-α receptor 1 and 2 (sTNFR1 and sTNFR2) (P < 0.001), and a significant decrease in serum high-sensitive C-reactive protein (P < 0.05). Positive correlations were observed between change (year 5 to baseline) in waist circumference and changes in high-sensitive C-reactive protein, orosomucoid (ORM), haptoglobin, and apolipoprotein B (ApoB) levels (0.26 ≤ r ≤ 0.34; P < 0.05), and between change in peripheral fat and changes in ORM, ApoB, sTNFR2 (0.28 ≤ r ≤ 0.39; P < 0.05). On the contrary, negative correlations were found between change in physical activity energy expenditure and changes in ORM as well as ApoB (r = -0.35 and r = -0.36, respectively; P < 0.05). No significant correlations were found between change in cardiorespiratory fitness, glucose, insulin, insulin sensitivity and changes in inflammatory markers. Multiple regression analyses showed that changes in physical activity energy expenditure and waist circumference together explained 23% of the individual variance of change in ORM (P < 0.05). Also, change in physical activity energy expenditure explained 15% (P < 0.05) of the variance of change in ApoB. Fat mass change explained 15% (P < 0.05) of the variance of change in IL-8, and finally change in peripheral fat explained 15% of variance of change in sTNFR2 (P < 0.05). The present study indicates that the menopausal transition is accompanied by an increase in inflammatory markers, namely ferritin, IL-8, sTNFR1, and sTNFR2. The increase in IL-8 and sTNFR2 with menopause could be explained, in part, by changes in fat mass and peripheral fat, respectively.

Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status.

In addition to its role in adaptive thermogenesis, brown adipose tissue (BAT) may protect from weight gain, insulin resistance/diabetes, and metabolic syndrome. Prior studies have shown contradictory results regarding the influence of thyroid hormone (TH) levels on BAT volume and activity. The aim of this pilot study was to gain further insights regarding the effect of TH treatment on BAT function in adult humans by evaluating the BAT mass and activity prospectively in six patients, first in the hypothyroid and then in the thyrotoxic phase. The study subjects underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scanning after cold exposure to measure BAT mass and activity while undergoing treatment for differentiated thyroid cancer, first while hypothyroid following TH withdrawal at the time of the radioactive iodine treatment and then three to six months after starting TH suppressive treatment when they were iatrogenically thyrotoxic. Thermogenic and metabolic parameters were measured in both phases. All study subjects had detectable BAT under cold stimulation in both the hypothyroid and thyrotoxic state. The majority but not all (4/6) subjects showed an increase in detectable BAT volume and activity under cold stimulation between the hypothyroid and thyrotoxic phase (total BAT volume: 72.0 ± 21.0 vs. 87.7 ± 16.5 mL, p = 0.25; total BAT activity 158.1 ± 72.8 vs. 189.0 ± 55.5 SUV*g/mL, p = 0.34). Importantly, circulating triiodothyronine was a stronger predictor of energy expenditure changes compared with cold-induced BAT activity. Iatrogenic hypothyroidism lasting two to four weeks does not prevent cold-induced BAT activation, while the use of TH to induce thyrotoxicosis does not consistently increase cold-induced BAT activity. It remains to be determined which physiological factors besides TH play a role in regulating BAT function.

Loss of UCP1 exacerbates Western diet-induced glycemic dysregulation independent of changes in body weight in female mice.

We tested the hypothesis that female mice null for uncoupling protein 1 (UCP1) would have increased susceptibility to Western diet-induced "whitening" of brown adipose tissue (AT) and glucose intolerance. Six-week-old C57BL/6J wild-type (WT) and UCP1 knockout (UCP1-/-) mice, housed at 25°C, were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 28 wk. Loss of UCP1 had no effect on energy intake, energy expenditure, spontaneous physical activity, weight gain, or visceral white AT mass. Despite similar susceptibility to weight gain compared with WT, UCP1-/- exhibited whitening of brown AT evidenced by a striking ~500% increase in mass and appearance of large unilocular adipocytes, increased expression of genes related to inflammation, immune cell infiltration, and endoplasmic reticulum/oxidative stress (P < 0.05), and decreased mitochondrial subunit protein (COX I, II, III, and IV, P < 0.05), all of which were exacerbated by Western diet (P < 0.05). UCP1-/- mice also developed liver steatosis and glucose intolerance, which was worsened by Western diet. Collectively, these findings demonstrate that loss of UCP1 exacerbates Western diet-induced whitening of brown AT, glucose intolerance, and induces liver steatosis. Notably, the adverse metabolic manifestations of UCP1-/- were independent of changes in body weight, visceral adiposity, and energy expenditure. These novel findings uncover a previously unrecognized metabolic protective role of UCP1 that is independent of its already established role in energy homeostasis.

Energy expenditure in frontotemporal dementia: a behavioural and imaging study.

SEE FINGER DOI101093/AWW312 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant frontotemporal dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant frontotemporal dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant frontotemporal dementia, 13 with Alzheimer's disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant frontotemporal dementia, resting (P = 0.001), stressed (P = 0.037) and sleeping heart rate (P = 0.038) were increased compared to control subjects, and resting heart rate (P = 0.020) compared to Alzheimer disease patients. Behavioural variant frontotemporal dementia was associated with decreased activity levels compared to controls (P = 0.002) and increased resting energy expenditure (P = 0.045) and total energy expenditure (P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke's Cognitive Examination). Increased resting heart rate in behavioural variant frontotemporal dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in frontotemporal dementia. These neural correlates overlap the network involved in eating behaviour in frontotemporal dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant frontotemporal dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis.

Changes in Energy Expenditure with Weight Gain and Weight Loss in Humans.

Metabolic adaptation to weight changes relates to body weight control, obesity and malnutrition. Adaptive thermogenesis (AT) refers to changes in resting and non-resting energy expenditure (REE and nREE) which are independent from changes in fat-free mass (FFM) and FFM composition. AT differs in response to changes in energy balance. With negative energy balance, AT is directed towards energy sparing. It relates to a reset of biological defence of body weight and mainly refers to REE. After weight loss, AT of nREE adds to weight maintenance. During overfeeding, energy dissipation is explained by AT of the nREE component only. As to body weight regulation during weight loss, AT relates to two different set points with a settling between them. During early weight loss, the first set is related to depleted glycogen stores associated with the fall in insulin secretion where AT adds to meet brain’s energy needs. During maintenance of reduced weight, the second set is related to low leptin levels keeping energy expenditure low to prevent triglyceride stores getting too low which is a risk for some basic biological functions (e.g., reproduction). Innovative topics of AT in humans are on its definition and assessment, its dynamics related to weight loss and its constitutional and neuro-endocrine determinants.

Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance

ObjectiveAdipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. MethodWhite and brown adipocyte-deficient (Hig2fl/fl × Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2fl/fl × Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots. Additionally, we used multiple housing temperatures to investigate the role of active brown/beige adipocytes in this process. ResultsHig2 localized to LDs in SGBS cells, a human adipocyte cell strain. Mice with adipocyte-specific Hig2 deficiency in all adipose depots demonstrated reduced visceral adipose tissue weight and increased glucose tolerance. This metabolic effect could be attributed to brown/beige adipocyte-specific Hig2 deficiency since Hig2fl/fl × Ucp1 cre+ mice displayed the same phenotype. Furthermore, when adipocyte-deficient Hig2 mice were moved to thermoneutral conditions in which non-shivering thermogenesis is deactivated, these improvements were abrogated and glucose intolerance ensued. Adipocyte-specific Hig2 deficient animals displayed no detectable changes in adipocyte lipolysis or energy expenditure, suggesting that Hig2 may not mediate these metabolic effects by restraining lipolysis in adipocytes. ConclusionsWe conclude that Hig2 localizes to LDs in adipocytes, promoting adipose tissue lipid deposition and that its selective deficiency in active brown/beige adipose tissue mediates improved glucose tolerance at 23 °C. Reversal of this phenotype at thermoneutrality in the absence of detectable changes in energy expenditure, adipose mass, or liver triglyceride suggests that Hig2 deficiency triggers a deleterious endocrine or neuroendocrine pathway emanating from brown/beige fat cells.

Platycodon grandiflorus Root Extract Attenuates Body Fat Mass, Hepatic Steatosis and Insulin Resistance through the Interplay between the Liver and Adipose Tissue.

The Platycodon grandiflorus root, a Korean medicinal food, is well known to have beneficial effects on obesity and diabetes. In this study, we demonstrated the metabolic effects of P. grandiflorus root ethanol extract (PGE), which is rich in platycodins, on diet-induced obesity. C57BL/6J mice (four-week-old males) were fed a normal diet (16.58% of kilocalories from fat), high-fat diet (HFD, 60% of kilocalories from fat), and HFD supplemented with 5% (w/w) PGE. In the HFD-fed mice, PGE markedly suppressed the body weight gain and white fat mass to normal control level, with simultaneous increase in the expression of thermogenic genes (such as SIRT1, PPARα, PGC1α, and UCP1), that accompanied changes in fatty acid oxidation (FAO) and energy expenditure. In addition, PGE improved insulin sensitivity through activation of the PPARγ expression, which upregulates adiponectin while decreasing leptin gene expression in adipocytes. Furthermore, PGE improved hepatic steatosis by suppressing hepatic lipogenesis while increasing expression of FAO-associated genes such as PGC1α. PGE normalized body fat and body weight, which is likely associated with the increased energy expenditure and thermogenic gene expression. PGE can protect from HFD-induced insulin resistance, and hepatic steatosis by controlling lipid and glucose metabolism.

A longitudinal examination of improved access on park use and physical activity in a low-income and majority African American neighborhood park.

This study sought to evaluate the impact of street crossing infrastructure modifications on park use and park-based physical activity in a low-income and African American community. A five-lane major highway created an access barrier between low-income housing units and the local neighborhood park in Columbia, Missouri. The installation of a signalized pedestrian crosswalk provided an opportunity to conduct a natural experiment to examine the effect of improved safe access upon community active living behaviors. Direct observation using SOPARC was collected prior to the crosswalk instillation in June 2012, after the crosswalk installation in June 2013 and again as a follow up in June 2014 during the same two-week period to assess changes in total park use and total energy expenditure by age, gender and race/ethnicity. Analysis of covariance models, controlling for temperature examined changes in total counts and total energy expenditure using pairwise Sidak post-hoc comparisons. Total park use increased from 2012 (n=2080) to 2013 (n=2275) and remained constant in 2014 (n=2276). However, despite increases in safe access and overall park use, there was a significant decrease in total energy expenditure following the installation of the crosswalk that was sustained in 2014. This study shows that increasing safe access to parks primarily positively influences park use but not park-based physical activity. While improved safe access is encouraging greater park use, there is a need for future research to examine additional factors such as social support, programming and environmental changes to engage community members in park-based physical activity.

Impact of metabolic syndrome on resting energy expenditure in patients with chronic kidney disease

Resting energy expenditure (REE) changes in patients with chronic kidney disease (CKD) may contribute to mortality increase. The obesity and inflammation is associated with high REE and when not compensated by adequate intake, may determine an unfavorable clinical outcome in this population. We aimed to evaluate the influence of metabolic syndrome (MetS) on REE in CKD patients. One hundred eighty-three patients were stratified according to glomerular filtration rate (GFR) and divided in groups: without CKD (GFR>60ml/min/1.73m2) and CKD (GFR<60ml/min/1.73m2) and according to the presence or absence of MetS. REE was measured by indirect calorimetry; body composition was assessed by bioelectrical impedance analysis and blood and urine were collected for biochemical tests. REE was lower in the group with CKD compared with those without CKD (1293±364 vs 1430±370kcal/d, P=0.01). The group with CKD without MetS showed decrease in REE compared to the groups without CKD, regardless the presence of Mets, and those with CKD and MetS (1173±315 vs 1392±324 vs 1460±410 vs 1424±376kcal/d, P<0.05, respectively). Multivariate analysis showed an independent association of CKD in determining REE when adjusted for lean body mass. The inclusion of MetS as an independent variable in the same analysis model neutralized the impact of CKD on the REE (P=0.19). Patients without MetS, REE correlated with estimated GFR and the protein equivalent (r=0.33, P<0.01, r=0.21, P=0.04, respectively), whereas in MetS patients, these correlations were not observed. The presence of CKD is independently associated with reduced REE. The observed decrease in REE is reversed in patients with MetS independent of renal function.