Adipose-derived stem cells (ADSCs) play critical roles in controlling obesity-associated inflammation and metabolic disorders. Exosomes from ADSCs exert protective effects in several diseases, but ...their roles in obesity and related pathological conditions remain unclear. In this study, we showed that treatment of obese mice with ADSC-derived exosomes facilitated their metabolic homeostasis, including improved insulin sensitivity (27.8% improvement), reduced obesity, and alleviated hepatic steatosis. ADSC-derived exosomes drove alternatively activated M2 macrophage polarization, inflammation reduction, and beiging in white adipose tissue (WAT) of diet-induced obese mice. Mechanistically, exosomes from ADSCs transferred into macrophages to induce anti-inflammatory M2 phenotypes through the transactivation of arginase-1 by exosome-carried active STAT3. Moreover, M2 macrophages induced by ADSC-derived exosomes not only expressed high levels of tyrosine hydroxylase responsible for catecholamine release, but also promoted ADSC proliferation and lactate production, thereby favoring WAT beiging and homeostasis in response to high-fat challenge. These findings delineate a novel exosome-mediated mechanism for ADSC-macrophage cross talk that facilitates immune and metabolic homeostasis in WAT, thus providing potential therapy for obesity and diabetes.
Physiological properties of water-soluble exopolysaccharides (EPS) and residues after EPS removal (Res) from the probiotic kefir were determined in high-fat (HF) diet-fed C57BL/6J mice. EPS solutions ...showed rheological properties and lower viscosity compared to those of β-glucan (BG). EPS significantly suppressed the adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner. Mice were fed HF diets containing 5% EPS, 5% BG, 8% Res, or 5% microcrystalline cellulose (control) for 4 weeks. Compared with the control, EPS supplementation significantly reduced HF diet-induced body weight gain, adipose tissue weight, and plasma very-low-density lipoprotein cholesterol concentration (P < 0.05). Res and BG significantly reduced body weight gain; however, reduction in adipose tissue weight was not statistically significant, suggesting that the antiobesity effect of EPS occurs due to viscosity and an additional factor. EPS supplementation significantly enhanced abundance of Akkermansia spp. in feces. These data indicate that EPS shows significant antiobesity effects possibly via intestinal microbiota alterations.
Aims
Ghrelin is implicated in the control of energy balance and glucose homeostasis. The ghrelin receptor exhibits ligand‐independent constitutive activity, which can be pharmacologically exploited ...to induce inverse ghrelin actions. Because ghrelin receptor inverse agonists (GHSR‐IA) might be effective for the treatment of obesity‐related metabolic disease, we tested 2 novel synthetic compounds GHSR‐IA1 and GHSR‐IA2.
Materials and Methods
In functional cell assays, electrophysiogical and immunohistochemical experiments, we demonstrated inverse agonist activity for GHSR‐IA1 and GHSR‐IA2. We used healthy mice, Zucker diabetic fatty (ZDF) rats and diet‐induced obese (DIO) mice to explore effects on food intake (FI), body weight (BW), conditioned taste aversion (CTA), oral glucose tolerance (OGT), pancreatic islet morphology, hepatic steatosis (HS), and blood lipids.
Results
Both compounds acutely reduced FI in mice without inducing CTA. Chronic GHSR‐IA1 increased metabolic rate in chow‐fed mice, suppressed FI, and improved OGT in ZDF rats. Moreover, the progression of islet hyperplasia to fibrosis in ZDF rats slowed down. GHSR‐IA2 reduced FI and BW in DIO mice, and reduced fasting and stimulated glucose levels compared with pair‐fed and vehicle‐treated mice. GHSR‐IA2‐treated DIO mice showed decreased blood lipids. GHSR‐IA1 treatment markedly decreased HS in DIO mice.
Conclusions
Our study demonstrates therapeutic actions of novel ghrelin receptor inverse agonists, suggesting a potential to treat obesity‐related metabolic disorders including diabetes mellitus.
There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from ...healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity.
FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance HOMA-IR between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus -3% ± 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention.
Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study.
ClinicalTrials.gov NCT02530385.
In the past decade, obesity has emerged as a major public health concern in the United States and abroad. At the federal, state, and local level, policy makers have begun drafting a range of policies ...to fight a war against fat, including body-mass index (BMI) report cards, "snack taxes," and laws to control how fast food companies market to children. As an epidemic, obesity threatens to weaken the health, economy, and might of the most powerful nation in the world.
InKiller Fat, Natalie Boero examines how and why obesity emerged as a major public health concern and national obsession in recent years. Using primary sources and in-depth interviews, Boero enters the world of bariatric surgeries, Weight Watchers, and Overeaters Anonymous to show how common expectations of what bodies are supposed to look like help to determine what sorts of interventions and policies are considered urgent in containing this new kind of disease.
Boero argues that obesity, like the traditional epidemics of biological contagion and mass death, now incites panic, a doomsday scenario that must be confronted in a struggle for social stability. The "war" on obesity, she concludes, is a form of social control.Killer Fatultimately offers an alternate framing of the nation's obesity problem based on the insights of the "Health at Every Size" movement.
The aim of the study was to investigate whether obese children and adolescents have a disturbed body representation as compared to normal-weight participants matched for age and gender and whether ...their body representation changes in the course of an inpatient weight-reduction program.
Sixty obese (OBE) and 27 normal-weight (NW) children and adolescents (age: 9-17) were assessed for body representation using a multi-method approach. Therefore, we assessed body size estimation, tactile size estimation, heartbeat detection accuracy, and attitudes towards one's own body. OBE were examined upon admission and before discharge of an inpatient weight-reduction program. NW served as cross-sectional control group.
Body size estimation and heartbeat detection accuracy were similar in OBE and NW. OBE overestimated sizes in tactile size estimation and were more dissatisfied with their body as compared to NW. In OBE but not in NW, several measures of body size estimation correlated with negative body evaluation. After weight-loss treatment, OBE had improved in heartbeat detection accuracy and were less dissatisfied with their body. None of the assessed variables predicted weight-loss success.
Although OBE children and adolescents generally perceived their body size and internal status of the body accurately, weight reduction improved their heartbeat detection accuracy and body dissatisfaction.
A variable percentage of children and adolescents with obesity do not have cardiometabolic comorbidities. A phenotype called metabolically healthy obese (MHO) has emerged to describe this population ...subgroup. Early identification of this condition may prevent the progression to metabolically unhealthy obesity (MUO).
A cross-sectional descriptive study of 265 children and adolescents from Cordoba (Spain) conducted in 2018. The outcome variables were MHO, established based on three criteria: International Criterion, HOMA-IR, and a combination of the previous two.
The prevalence of MHO ranged from 9.4% to 12.8% of the study population, between 41% and 55.7% of the sample with obesity. The highest agreement was reached between the HOMA-IR definitions and the combined criteria. The waist-to-height ratio (WHtR) was the indicator with the highest discriminant capacity for MHO in 2 of the three criteria, with its best cut-off point at 0.47 for both.
The prevalence of MHO in children and adolescents differed according to the criteria used for diagnosis. The anthropometric variable with the most remarkable discriminating capacity for MHO was WHtR, with the same cut-off point in the three criteria analysed.
This research work defines the existence of metabolically healthy obesity through anthropometric indicators in children and adolescents. Definitions that combine cardiometabolic criteria and insulin resistance are used to identify metabolically healthy obesity, as well as the prediction of this phenomenon through anthropometric variables. The present investigation helps to identify metabolically healthy obesity before metabolic abnormalities begin.
: The rising prevalence of obesity represents an important public health issue. An assessment of its costs may be useful in providing recommendations for policy and decision makers. This systematic ...review aimed to assess the economic burden of obesity and to identify, measure and describe the different obesity-related diseases included in the selected studies.
: A systematic literature search of studies in the English language was carried out in Medline (PubMed) and Web of Science databases to select cost-of-illness studies calculating the cost of obesity in a study population aged ≥18 years with obesity, as defined by a body mass index of ≥30 kg/m², for the whole selected country. The time frame for the analysis was January 2011 to September 2016.
: The included twenty three studies reported a substantial economic burden of obesity in both developed and developing countries. There was considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives. This prevents an informative comparison between most of the studies. Specifically, there was great variety in the included obesity-related diseases and complications among the studies.
: There is an urgent need for public health measures to prevent obesity in order to save societal resources. Moreover, international consensus is required on standardized methods to calculate the cost of obesity to improve homogeneity and comparability. This aspect should also be considered when including obesity-related diseases.
Maternal obesity is strongly associated with offspring obesity risk. However, studies show that paternal obesity also affects offspring phenotype, especially in males. Programming of the growth ...hormone (GH) insulin-like growth factor (IGF) axis seems to be an important mechanism in this finding, but evidence regarding this relationship in humans is scarce. The primary purpose of this study was to evaluate associations between maternal and paternal adiposity with that of their offspring. A secondary aim was to investigate associations between paternal adiposity with GH levels in male offspring.
Parent-offspring trios (n = 209) from the Glowing study were studied. Percent body fat mass (%FM) was measured using air displacement plethysmography early in pregnancy in parents, and at age 2 weeks in the offspring. Plasma GH levels were measured at birth from umbilical cord blood (n = 31) and at age 2 years (n = 39) in male offspring. Multiple linear regression was used to model infant’s %FM (dependent variable) at 2 weeks of age using parental %FM, race, age, IQ, income, delivery method, gestational weight gain, feeding mode, and gestational age (GA) as independent variables. The best fitted models were constructed for girls and boys. Spearman correlations (ρ) between paternal %FM and offspring GH levels were adjusted for maternal %FM.
Girls (n = 94): Paternal %FM did not associate with female newborn %FM. Instead, maternal %FM (β = 0.12, P = 0.010) and C-section delivery mode (β = 2.56, P = 0.011) had the strongest associations with female newborn %FM. Boys (n = 115): Maternal %FM (β = 0.12, P = 0.006) and GA (β = 1.06, P = 0.003) were positively associated with male newborn %FM, whereas paternal %FM was negatively associated (β = −0.09, P = 0.014) with male offspring adiposity. There was no significant correlation between paternal %FM and GH measured at birth (ρ = 0.19, P = NS) in boys. However, at age 2 years, GH levels in boys decreased with increasing paternal %FM (ρ = −0.40, P = 0.015). Maternal %FM did not correlate with offspring GH level at any age.
Parental obesity differentially associates with newborn girls’ and boys’ adiposity at age 2 weeks. In line with prior findings in animal models, this preliminary analysis points to programming of the GH/IGF axis in male offspring born to obese fathers.
USDA ARS # 6026-51000-010-05S, NIH 1UL1RR029884.
We aimed to evaluate the association between Chinese visceral adiposity index (CVAI), a body shape index (ABSI) and diabetes in Chinese adults; we further assessed the predictive capacity of ...CVAI/ABSI for diabetes by comparing with various anthropometric adiposity indices.
We used the data of 5838 Chinese men and women aged ≥18 years from the China Health and Nutrition Survey 2009. Subjects were divided into subgroups according to CVAI and ABSI quartiles. Multivariate logistic regression analysis was performed to examine the independent associations between CVAI/ABSI and diabetes; we assessed the predictive power of the two indexes using the receiver-operating characteristic (ROC) curve analysis.
Both CAVI and ABSI were positively associated with diabetes. In multivariable model, the odds ratios (ORs) (95% confidence intervals) for diabetes across quartiles of CAVI were, 1.00, 1.9 (1.1–3.3), 2.3 (1.4–3.9), and 4.9 (2.9–8.1) in men and 1.00, 3.0 (1.1–8.2), 7.7 (2.9–21.0) and 14.2 (5.3–38.2) in women, respectively. The corresponding figures across quartiles of ABSI were 1.00, 1.2 (0.8–1.9), 1.6 (1.1–2.4) and 1.8 (1.2–2.8) in men, and 1.00, 1.2 (0.7–1.9), 1.7 (1.1–2.7) and 2.0 (1.3–3.1) in women, respectively. The area under ROC (AUC) for CVAI was the highest among all examined indices including ABSI, BMI and WC, with AUCs of 0.729 (0.696–0.762) and 0.794 (0.767–0.818) for identifying diabetes risk in men and women, respectively. ABSI had a similar AUC as BMI.
Higher CVAI and ABSI scores are independently associated with diabetes risk; The CVAI is a better indicator of diabetes than BMI, waist circumference and ABSI in Chinese adults.
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