Caloric Restriction Prevents Metabolic Dysfunction and the Changes in Hypothalamic Neuropeptides Associated with Obesity Independently of Dietary Fat Content in Rats.

Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levels.

Advances in Understanding of the Role of Lipid Metabolism in Aging.

During aging, body adiposity increases with changes in the metabolism of lipids and their metabolite levels. Considering lipid metabolism, excess adiposity with increased lipotoxicity leads to various age-related diseases, including cardiovascular disease, cancer, arthritis, type 2 diabetes, and Alzheimer's disease. However, the multifaceted nature and complexities of lipid metabolism make it difficult to delineate its exact mechanism and role during aging. With advances in genetic engineering techniques, recent studies have demonstrated that changes in lipid metabolism are associated with aging and age-related diseases. Lipid accumulation and impaired fatty acid utilization in organs are associated with pathophysiological phenotypes of aging. Changes in adipokine levels contribute to aging by modulating changes in systemic metabolism and inflammation. Advances in lipidomic techniques have identified changes in lipid profiles that are associated with aging. Although it remains unclear how lipid metabolism is regulated during aging, or how lipid metabolites impact aging, evidence suggests a dynamic role for lipid metabolism and its metabolites as active participants of signaling pathways and regulators of gene expression. This review describes recent advances in our understanding of lipid metabolism in aging, including established findings and recent approaches.

Significant Impact of Coffee Consumption on MR-Based Measures of Cardiac Function in a Population-Based Cohort Study without Manifest Cardiovascular Disease.

Subclinical effects of coffee consumption (CC) with regard to metabolic, cardiac, and neurological complications were evaluated using a whole-body magnetic resonance imaging (MRI) protocol. A blended approach was used to estimate habitual CC in a population-based study cohort without a history of cardiovascular disease. Associations of CC with MRI markers of gray matter volume, white matter hyperintensities, cerebral microhemorrhages, total and visceral adipose tissue (VAT), hepatic proton density fat fraction, early/late diastolic filling rate, end-diastolic/-systolic and stroke volume, ejection fraction, peak ejection rate, and myocardial mass were evaluated by linear regression. In our analysis with 132 women and 168 men, CC was positively associated with MR-based cardiac function parameters including late diastolic filling rate, stroke volume (p < 0.01 each), and ejection fraction (p < 0.05) when adjusting for age, sex, smoking, hypertension, diabetes, Low-density lipoprotein (LDL), triglycerides, cholesterol, and alcohol consumption. CC was inversely associated with VAT independent of demographic variables and cardiovascular risk factors (p < 0.05), but this association did not remain significant after additional adjustment for alcohol consumption. CC was not significantly associated with potential neurodegeneration. We found a significant positive and independent association between CC and MRI-based systolic and diastolic cardiac function. CC was also inversely associated with VAT but not independent of alcohol consumption.

Adiposity and pathogen exposure: An investigation of response to iron supplementation and hypothesized predictors in anemic pre-school-aged children living in a dual burden environment.

OBJECTIVES: Peruvians are experiencing rapid dietary and lifestyle changes, resulting in a phenomenon known as the "dual burden of disease." A common manifestation of the dual burden in individuals is the co-occurrence of overweight and anemia. Despite recent initiatives introduced to address these concerns, rates continue to be public health concerns. This study investigates the relationship between immune activation and lack of response to iron supplementation after 1 month of treatment and explores variation in body fat stores as a potential moderator between immune function and response to treatment. METHODS: Data come from children, aged 2-5 years (n = 50) from a peri-urban community in Lima, Peru. Multivariate logistic regression models were used to explore the associations between response to treatment (Hb > =11.0 g/dl) after 1 month of treatment), markers of immune activation (C-reactive protein [CRP] and reported morbidity symptoms), and measures of body fat (waist-to-height ratio, triceps skinfold thickness, and body mass index [BMI]). RESULTS: We found that high CRP is associated with a lack of response to iron supplementation after 1 month of treatment and that BMI z-score may moderate this association. Generally, larger body size is associated with response to iron supplementation whether or not the children in this sample have high immune activation. However, the probability of anemic children responding to iron supplementation treatment differed across adiposity measures. CONCLUSIONS: Our finding suggesting that adiposity and CRP influence response to iron supplementation, furthers our understanding of the relationship between inflammation and anemia treatment in children and has both theoretical and public health implications.

The association of actigraphic sleep measures and physical activity with excess weight and adiposity in kindergarteners.

Insufficient sleep duration and physical activity (PA) are known risk factors for overweight and obesity in children; however, there are no studies on comprehensive associations of objectively-measured sleep parameters and PA with excess weight and excess adiposity in kindergarteners. Therefore, the aim of this study was to determine the associations between objectively measured sleep parameters and PA with excess weight and excess adiposity, defined as BMI ≥ 85th percentile and body fat percentage (BFP) ≥ 85th percentile, respectively. Sleep parameters and PA were measured in 676 subjects aged 5-6 years using accelerometers for 7 days, worn at the participant's hip. Bioelectrical impedance analysis was used to estimate BFP. In the total sample, lower sleep duration, sleep efficiency, vigorous PA and the number of steps per day were associated with excess weight. However, excess adiposity was associated with lower sleep duration, total PA, vigorous PA, moderate-to-vigorous physical activity (MVPA) and the number of steps per day. Logistic regression by the stepwise progressive method showed that the strongest predictor of excess adiposity in boys and girls was vigorous PA, while the strongest predictor of excess weight in boys was sleep efficiency. A holistic approach to health targeting all of these factors synergistically is needed to optimize the effectiveness of obesity prevention and treatment interventions.

High placental inositol content associated with suppressed pro-adipogenic effects of maternal glycaemia in offspring: the GUSTO cohort.

BACKGROUND/OBJECTIVES: Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels. METHODS: Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks' gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed. RESULTS: Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted ß [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [-21.2, 183.2], AAT = 0.8 ml [-8.4, 10.0]). CONCLUSIONS: High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.

Yellow Tea Stimulates Thermogenesis in Mice through Heterogeneous Browning of Adipose Tissues.

SCOPE: Large-leaf yellow tea (YT) exhibits interesting beneficial metabolic effects in previous studies. Here, the authors elucidated the actions of YT on thermogenesis, energy metabolism, and adipocyte metabolic conversion. METHODS AND RESULTS: Five-week-old male C57BL/6 mice are fed low-fat diet, high-fat diet (HFD), and HFD supplemented with 0.5% or 2.5% YT. After treatment for 10 or 14 weeks, YT enhances energy expenditure, O2 consumption and CO2 production. YT strongly boosts thermogenic program in brown adipose tissue (BAT) and subcutaneous adipose tissue (SAT), while only weakly in epididymal adipose tissue (EAT). These are accompanied by higher body temperature, increased mitochondrial copy numbers, and upregulation of thermogenic genes (Ucp1, Pgc1α, etc.) and proteins. The classic brown adipocyte markers (Eva1, Zic1) are induced only in BAT, while beige adipocyte markers (Tbx1, Tmem26) are boosted only in SAT. Furthermore, subcutaneous-originated preadipocytes are induced by YT in vitro to differentiate to brown-like adipocytes - a browning effect. CONCLUSION: Dietary YT induces adaptive thermogenesis through increasing mitochondrial biogenesis in EAT, inducing beigeing in SAT and enhancing browning in the BAT.

The association of plant-based dietary patterns with visceral adiposity, lipid accumulation product, and triglyceride-glucose index in Iranian adults.

BACKGROUND: We sought to investigate whether adherence to a more plant-based, and less animal-based, diet is associated with visceral adiposity, lipid accumulation product (LAP), and triglyceride-glucose index (TyG) in Iranian adults. METHODS: This cross-sectional study was conducted on 270 adults aged between 18-75 years old. We created three plant-based diets. including an overall plant-based diet index (PDI), hPDI, and uPDI based on tertiles regarding the intake of animal- or plant-based food items obtained from a semi quantitative food-frequency questionnaire. RESULTS: Higher hPDI was significantly associated with lower body mass index (BMI) (P-value = 0.01), lower waist circumference (P-value<0.001), and lower waist-hip ratio (P-value<0.001). A significant increase was found for high density lipoproteins (HDL) (P-trend <0.001) with a significant decrease for LAP (P-value = 0.03) in those with higher adherence to hPDI. Moreover, greater adherence to PDI was associated with a significant increase in diastolic blood pressure (DBP) (p-value = 0.01) and fat free mass (FFM) (p-value = 0.01). There were no significant associations between PDIs and TyG and VFA. CONCLUSION: We found that a higher hPDI score was significantly associated with better anthropometric measurements. A significant increase was found for HDL and a significant decrease was found for LAP on hPDI. However, a higher PDI score was significantly associated with higher DBP and higher FFM.

Exogenous Dietary Ketone Ester Decreases Body Weight and Adiposity in Mice Housed at Thermoneutrality.

OBJECTIVE: The aim of this study was to examine the effects of a ketone ester (KE)-supplemented diet on energy expenditure (EE) and adiposity in mice housed at 23 °C versus thermoneutrality (30 °C), in which sympathetic nervous system activity is diminished. METHODS: Thirty-two 10-week-old male C57BL/6J mice were assigned to 1 of 4 groups (n = 8 per group): 30% KE diet + 23 °C (KE23), control (CON) diet + 23 °C (CON23), 30% KE diet + 30 °C (KE30), or CON diet + 30 °C (CON30). CON mice were pair-fed to the average intake of mice consuming the KE diet (ad libitum) for 8 weeks. Body composition and components of energy balance were measured at completion of the study. RESULTS: CON23 (mean ± SD, 26.0 ± 1.6 g) and CON30 (29.7 ± 1.4 g) mice weighed more than KE groups (P < 0.03 for both) and were also different from each other (CON23 vs. CON30, P < 0.01). However, KE23 (23.4 ± 2.7 g) and KE30 (23.1 ± 1.9 g) mice were not different in body weight. As expected, food intake at 30 °C (2.0 ± 0.3 g/d) was lower than at 23 °C (2.6 ± 0.3 g/d, P < 0.01). Diet did not influence resting and total EE, but mice housed at 30 °C had lower EE compared with mice at 23 °C (P < 0.01). CONCLUSIONS: Dietary KEs attenuate body weight gain at standard (23 °C) and thermoneutral (30 °C) housing temperatures, and this effect is not mediated by increased EE under these conditions.

Weight Loss after 12 Weeks of Exercise and/or Nutritional Guidance Is Not Obligatory for Induced Changes in Local Fat/Lean Mass Indexes in Adults with Excess of Adiposity.

The objectives of this secondary analysis are (1) to investigate the differential effects of exercise training modalities-high-intensity interval training (HIIT), resistance training (RT), combined training (CT = HIIT + RT), and/or nutritional guidance (NG) alone-on local fat/lean mass indexes in adults with excess of adiposity; (2) to identify the individual patterns of response based on either a clinical criterion of weight loss (≥5%) and/or technical error (TE) of measurement of local fat/lean mass indexes; and (3) to assess the individual change for body composition parameters assigned either to HIIT, RT, CT, and/or NG groups utilizing a TE. A 12-week trial was conducted in 55 participants randomized to one of the four interventions. The primary outcome was clinical change in body weight (i.e., weight loss of ≥5%). Secondary outcomes included change in ratio of android and gynoid fat mass, as well as local fat and lean mass indexes (arms, trunk, and legs), before and after intervention. The main findings from the current analysis revealed that (i) after 12 weeks of follow-up, significant decreases in several body composition indexes were found including body weight, arm, trunk, and legs fat mass, and android and gynecoid fat mass were observed in HIIT, RT, and CT groups (p < 0.05); (ii) a significant proportion of individuals showed a positive response following 12 weeks of training, led by the HIIT group with 44% and followed by RT with 39% in 9 indexes; (iii) the HIIT group showed lowest rates of adverse responders with (6%); and (iv) the individual patterns of response utilizing clinically meaningful weight loss were not necessarily associated with the corresponding individual training-induced changes in body composition indexes in adults with excess of adiposity. Overall, the study suggests that HIIT has an important ability to reduce the prevalence of non-response to improve body composition indexes.

The effect of green tea supplementation on obesity: A systematic review and dose-response meta-analysis of randomized controlled trials.

The effects of green tea (GT) in obese subjects have been evaluated in different studies, but no consensus has been obtained due to the heterogeneity of the results. The dosage, the type of extract, and the duration of the intervention are the main contributors to the heterogeneity of the results. Therefore, the present systematic review and meta-analysis aimed to evaluate the efficacy and dose-response relationship of GT. Several databases were searched from inception to September 2019 to identify clinical trials that examined the influence of GT supplements on obesity indices in humans. Combined results using the random-effects model indicated that body weight (WMD: -1.78 kg, 95% CI: -2.80, -0.75, p = .001) and body mass index (BMI) (WMD: -0.65 kg/m2 , 95% CI: -1.04, -0.25, p = .001) did change significantly following GT administration. The reduction in waist circumference (WC) after GT consumption was significant in subjects in trials employing GT ≥800 mg/day (WMD: -2.06 cm) and with a treatment duration <12 weeks (WMD: -2.39 cm). Following the dose-response evaluation, GT intake did alter body weight, with a more important reduction when the GT dosage was <500 mg/day and the treatment duration was of 12 weeks. The results of present meta-analysis study support the use of GT for the improvement of obesity indices. Thus, we suggest that the use of GT can be combined with a balanced and healthy diet and regular physical exercise in the management of obese patients.

BRS3 in both MC4R- and SIM1-expressing neurons regulates energy homeostasis in mice.

OBJECTIVE: Bombesin-like receptor 3 (BRS3) is an orphan receptor and Brs3 knockout mice develop obesity with increased food intake and reduced resting metabolic rate and body temperature. The neuronal populations contributing to these effects were examined. METHODS: We studied energy metabolism in mice with Cre-mediated recombination causing 1) loss of BRS3 selectively in SIM1- or MC4R-expressing neurons or 2) selective re-expression of BRS3 from a null background in these neurons. RESULTS: The deletion of BRS3 in MC4R neurons increased body weight/adiposity, metabolic efficiency, and food intake, and reduced insulin sensitivity. BRS3 re-expression in these neurons caused partial or no reversal of these traits. However, these observations were confounded by an obesity phenotype caused by the Mc4r-Cre allele, independent of its recombinase activity. The deletion of BRS3 in SIM1 neurons increased body weight/adiposity and food intake, but not to the levels of the global null. The re-expression of BRS3 in SIM1 neurons reduced body weight/adiposity and food intake, but not to wild type levels. The deletion of BRS3 in either MC4R- or SIM1-expressing neurons affected body temperature, with re-expression in either population reversing the null phenotype. MK-5046, a BRS3 agonist, increases light phase body temperature in wild type, but not Brs3 null, mice and BRS3 re-expression in either population restored response to MK-5046. CONCLUSIONS: BRS3 in both MC4R- and SIM1-expressing neurons contributes to regulation of body weight/adiposity, insulin sensitivity, food intake, and body temperature.

Association of Hot Tea Consumption with Regional Adiposity Measured by Dual-Energy X-Ray Absorptiometry in NHANES 2003-2006.

OBJECTIVE: This study aimed to investigate the potential antiobesity benefits of hot tea consumption at the population level. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, the association between hot tea consumption and dual-energy x-ray-measured body fat was examined in a large representative sample of US adults (n = 5,681, 51.9% women). RESULTS: Compared with non-tea drinkers, men who consumed 0.25 to 1 cup per day of hot tea had 1.5% (95% CI: 0.4% to 2.6%) and 1.7% (95% CI: 0.4% to 3.0%) less total and trunk body fat, respectively. The associations were stronger among men 45 to 69 years old compared with younger men (20-44 years). For men who consumed 1 or more cups per day of hot tea, lower total (-1.2%, 95% CI: -2.3% to -0.2%) and trunk body fat (-1.3%, 95% CI: -2.6 to -0.1%) was observed among men 45 to 69 years old only. In women, those who drank 1 or more cups per day had 1.5% lower (95% CI: -2.7% to -0.3%) trunk body fat compared with non-tea drinkers. CONCLUSIONS: Consumption of hot tea might be considered as part of a healthy diet in order to support parameters associated with metabolic health and may be particularly important in older male age groups in supporting reduced central adiposity.

Neonatal nutritional programming induces gliosis and alters the expression of T-cell protein tyrosine phosphatase and connexins in male rats.

Changes to neonatal nutrition result in long-lasting impairments in energy balance, which may be described as metabolic programing. Astrocytes, which are interconnected by gap junctions, have emerged as important players in the hypothalamic control of food intake. In order to study the effects of nutritional programming on glial morphology and protein expression, cross-fostered male Wistar rats at postnatal day 3 were assigned to three groups based on litter size: small litter (3 pups per dam, SL), normal litter (10 pups per dam, NL), and large litter (16 pups per dam, LL). Rats from the SL group exhibited higher body weight throughout the study and hyperphagia after weaning. LL animals exhibited hyperphagia, high energy efficiency and catch-up of body weight after weaning. Both the SL and LL groups at postnatal day 60 (PN60) exhibited increased levels of plasma leptin, the Lee index (as an index of obesity), adiposity content, immunoreactivity toward T-cell protein tyrosine phosphatase (TCPTP), and glial fibrillary acidic protein (GFAP) in the arcuate nucleus (ARC) of the hypothalamus. Astrocyte morphology was altered in the ARC of SL and LL animals, and this effect occurred in parallel with a reduction in immunoreactivity toward connexin 30 (CX30). The data obtained demonstrate that both neonatal over- and underfeeding promote not only alterations in the metabolic status but also morphological changes in glial cells in parallel with increasing TCPTP and changes in connexin expression.

Relationship Between Modified Body Adiposity Index and A Body Shape Index with Biochemical Parameters in Bariatric Surgery Candidates.

BACKGROUND: Body mass index, an estimate of body fat percentage, has been previously shown to be associated with metabolic disorders. However, there is little data on the associations between a body shape index (ABSI) or modified body adiposity index (MBAI), which provide valuable definitions of body fat, with serum biochemical parameter levels. Therefore, this study was conducted to find either ABSI or MBAI associations with serum biochemical parameter levels in bariatric surgery candidates. METHODS: This cross-sectional study was conducted on 776 bariatric surgery candidates (age range 18-69 years) between November 2010 and September 2017. Demographic data, anthropometric indices, biochemical parameters, and body composition analysis data were drawn from the National Obesity Surgery Database, Iran. ABSI and MBAI were calculated using related equations. A stepwise multivariate linear regression was used to evaluate whether ABSI or MBAI was associated with each serum biochemical parameter. RESULTS: ABSI, age, and multivitamin/mineral supplementation (MVMS) were independently associated with serum vitamin D (ß = 24.374, SE 10.756, P value 0.026; ß = 0.022, SE 0.007, P value 0.002; ß = 0.639, SE 0.235, P value 0.008). However, a negative association was observed between MBAI and vitamin D (ß = - 0.037, SE 0.016, P value 0.025) in a model adjusted for age and MVMS. Additionally, MBAI and age showed a significant positive association with serum HDL-c (ß = 0.185, SE 0.085, P value 0.028; ß = 0.171, SE 0.033, P value < 0.001), although there was a negative association between male sex and HDL-c (ß = - 4.004, SE 0.891, P value < 0.001). CONCLUSION: ABSI and MBAI may be appropriate indices in predicting serum vitamin D and HDL-c levels.

The effects of dietary fatty acids in the physiological outcomes of maternal high-fat diet on offspring energy homeostasis in mice.

The early-life origins of disease hypothesis has been applied to obesity research and modeled through overnutrition, usually with a high-fat diet (HFD). Since the obesity epidemic coincided with societal change in dietary fat consumption, rather than amount, manipulation of fatty acid (FA) profile is an under-investigated area of study. Additionally, the binding of FAs to nuclear receptors may have persistent intergenerational, extranutritive endocrinological effects that interact with the actions of reproductive steroids causing sex-dependent effects. To determine the role of FA type in the effects underlying maternal HFD, we fed wild-type C57BL6/J mating pairs, from preconception through lactation, a HFD with high saturated fat levels from coconut oil or high linoleic acid (LA) levels from vegetable oil. Male and female offspring body weight and food intake were measured weekly for 25 weeks. Assays for glucose metabolism, body composition, and calorimetry were performed at 25 weeks. Plasma metabolic peptides and liver mRNA were measured terminally. Obesity was primarily affected by adult rather than maternal diet in males, yet in females, maternal HFD potentiated the effects of adult HFD. Maternal HFD high in LA impaired glucose disposal in males weaned onto HFD and insulin sensitivity of females. Plasma leptin correlated with adiposity, but insulin and insulin receptor expression in the liver were altered by maternal LA in males. Our results suggest that maternal FA profile is most influential on offspring glucose metabolism and that adult diet is more important than maternal diet for obesity and other parameters of metabolic syndrome.

Sex differences in the peripubertal response to a short-term, high-fat diet intake.

Obesity is one of the most important health problems facing developed countries because being overweight is associated with a higher incidence of type 2 diabetes, cardiovascular disease and cancer, as well as other comorbidities. Although increased weight gain results from a combination of poor dietary habits and decreased energy expenditure, not all individuals have equal propensities to gain weight or to develop secondary complications of obesity. This is partially a result not only of genetics, including sex, but also the time during which an individual is exposed to an obesogenic environment. In the present study, we have compared the response of male and female mice to short-term exposure to a high-fat diet (HFD) or a low-fat diet during the peripubertal period (starting at 42 days of age) because this is a stage of dramatic hormonal and metabolic modifications. After 1 week on a HFD, there was no significant increase in body weight, although females significantly increased their energy intake. Serum leptin levels increased in both sexes, even though no change in fat mass was detected. Glyceamia and homeostasis model assessment increased in males, suggesting a rapid change in glucose metabolism. Hypothalamic pro-opiomelanocortin mRNA levels were significantly higher in females on a HFD compared to all other groups, which may be an attempt to reduce their increased energy intake. Hypothalamic inflammation and gliosis have been implicated in the development of secondary complications of obesity; however, no indication of activation of inflammatory processes or gliosis was found in response to 1 week of HFD in the hypothalamus, hippocampus or cerebellum of these young mice. These results indicate that there are both sex and age effects in the response to poor dietary intake because peripubertal male and female mice respond differently to short-term dietary changes and this response is different from that reported in adult rodents.

STAT5 ablation in AgRP neurons increases female adiposity and blunts food restriction adaptations.

AgRP neurons are important players in the control of energy homeostasis and are responsive to several hormones. In addition, STAT5 signalling in the brain, which is activated by metabolic hormones and growth factors, modulates food intake, body fat and glucose homeostasis. Given that, and the absence of studies that describe STAT5 function in AgRP cells, the present study investigated the metabolic effects of Stat5a/b gene ablation in these neurons. We observed that STAT5 signalling in AgRP neurons regulates body fat in female mice. However, male and female STAT5-knockout mice did not exhibit altered food intake, energy expenditure or glucose homeostasis compared to control mice. The counter-regulatory response or glucoprivic hyperphagia induced by 2-deoxy-d-glucose treatment were also not affected by AgRP-specific STAT5 ablation. However, under 60% food restriction, AgRP STAT5-knockout mice had a blunted upregulation of hypothalamic Agrp mRNA expression and corticosterone serum levels compared to control mice, suggesting a possible role for STAT5 in AgRP neurons for neuroendocrine adaptations to food restriction. Interestingly, ad libitum fed knockout male mice had reduced Pomc and Ucp-1 mRNA expression compared to control group. Taken together, these results suggest that STAT5 signalling in AgRP neurons regulates body adiposity in female mice, as well as some neuroendocrine adaptations to food restriction.

MCH Regulates SIRT1/FoxO1 and Reduces POMC Neuronal Activity to Induce Hyperphagia, Adiposity, and Glucose Intolerance.

Melanin-concentrating hormone (MCH) is an important regulator of food intake, glucose metabolism, and adiposity. However, the mechanisms mediating these actions remain largely unknown. We used pharmacological and genetic approaches to show that the sirtuin 1 (SIRT1)/FoxO1 signaling pathway in the hypothalamic arcuate nucleus (ARC) mediates MCH-induced feeding, adiposity, and glucose intolerance. MCH reduces proopiomelanocortin (POMC) neuronal activity, and the SIRT1/FoxO1 pathway regulates the inhibitory effect of MCH on POMC expression. Remarkably, the metabolic actions of MCH are compromised in mice lacking SIRT1 specifically in POMC neurons. Of note, the actions of MCH are independent of agouti-related peptide (AgRP) neurons because inhibition of γ-aminobutyric acid receptor in the ARC did not prevent the orexigenic action of MCH, and the hypophagic effect of MCH silencing was maintained after chemogenetic stimulation of AgRP neurons. Central SIRT1 is required for MCH-induced weight gain through its actions on the sympathetic nervous system. The central MCH knockdown causes hypophagia and weight loss in diet-induced obese wild-type mice; however, these effects were abolished in mice overexpressing SIRT1 fed a high-fat diet. These data reveal the neuronal basis for the effects of MCH on food intake, body weight, and glucose metabolism and highlight the relevance of SIRT1/FoxO1 pathway in obesity.

Effect of Ramadan diurnal fasting on visceral adiposity and serum adipokines in overweight and obese individuals.

AIM: Excessive visceral adiposity is a major risk factor for developing insulin resistance and systemic low-grade inflammation. Ramadan diurnal fasting (RDF) is a religious ritual practiced by more than one billion Muslim throughout the world. It has been considered as one of the most common types of complementary and integrative health practices. The aim of this study is to examine the impact of RDF on visceral adiposity, circulating adipokines and glucoregulatory markers in patients with overweight or obesity. METHODS: Overweight and obese subjects (n = 61; 23 men and 38 women) were included in the study. Body weight, visceral fat tissue area (measured by 3D-MRI), glucoregulatory factors, serum adipokines concentrations, dietary intake, and physical activity were assessed one week before and at the end of the lunar month of Ramadan. RESULTS: From baseline, body weight and visceral fat tissue area serum total cholesterol, triglycerides, HDL-cholesterol, and systolic blood pressure significantly decreased (P < 0.05 for each) at the end of Ramadan. The serum levels of adiponectin, IL-6, TNF-α, and IGF-1 significantly decreased (P < 0.05 for each), but serum visfatin, leptin, apelin, IL-10, and IL-10/IL-6 ratio significantly increased (P < 0.05 for each) at the end of Ramadan. Changes in visceral adiposity significantly correlated with changes in plasma glucose (r = 0.4, P < 0.5) and resistin (r = 0.44, P < 0.001) at the end of Ramadan. CONCLUSION: RDF lowers visceral adiposity, body weight and variably affects adipokines without adversely affecting markers of glucose homeostasis in individuals with overweight or obesity.