Increased Adipose Tissue Mass Research Articles

Genetic deletion of ITIH5 leads to increased development of adipose tissue in mice

BackgroundAdipocytokines play a pivotal role in maintaining adipose tissue homeostasis by regulating cellular metabolism, proliferation, differentiation, and secretory activity. These soluble factors are relevant components for healthy adipose tissue, while their deficiency is closely associated with the development of obesity and related metabolic diseases, e.g., chronic inflammation. In human adipose tissue, inter-α-trypsin inhibitor heavy chain 5 (ITIH5) is expressed in proportion to the development of adipose tissue, i.e., the individual’s BMI. Thus, ITIH5 has been proposed to be an inert marker of human obesity. However, when applied to adipose stem cells in vitro, recombinant (r)ITIH5 protein inhibited proliferation and adipogenesis, suggesting that ITIH5 negatively affects the development of fat mass. We now tested the role of ITIH5 in vivo and compared ITIH5+/+ wildtype with ITIH5−/− knockout mice.ResultsGenetic deletion of ITIH5 significantly increased adipose tissue mass relative to animal bodyweight (p < 0.05). Next, we characterized adipose stem cells (ASCs) from both genotypes in vitro. ITIH5−/− cells exhibited increased proliferation and adipogenic differentiation (p < 0.001), which could explain the increase in adipose tissue in vivo. Furthermore, ASCs from ITIH5−/− animals were more responsive to stimulation with inflammatory mediators, i.e., these cells released greater amounts of IL-6 and MCP-1 (p < 0.001). Importantly, the application of the rITIH5 protein reversed the observed knockout effects in ASCs.ConclusionsOur data suggest that ITIH5 potently regulates adipose tissue development and homeostasis by modulating ASC biology in mice. In addition, the effect of the rITIH5 protein underscores its potential as a therapeutic agent to correct the adipose tissue dysregulation often associated with obesity and metabolic disorders.

The effects of high-intensity interval training/moderate-intensity continuous training on the inhibition of fat accumulation in rats fed a high-fat diet during training and detraining

BackgroundCompared with moderate-intensity continuous training (MICT), high-intensity interval training (HIIT) has at least a comparable effect on inhibiting an increase in fat. However, few studies have been conducted to examine the effects of detraining on body fat in rats fed a high-fat diet. The present study aimed to compare the effects of 10 weeks of HIIT or MICT as well as 6 weeks of detraining on body fat in rats fed a high-fat diet.MethodsAfter being fed a high-fat diet for 8 weeks, 54 female rats were randomly assigned to six groups: (1) CON-10, sedentary control for 10 weeks; (2) MICT-10, 10 weeks of MICT; (3) HIIT-10, 10 weeks of HIIT; (4) CON-16, sedentary control for 16 weeks; (5) MICT-16, 10 weeks of MICT followed by 6 weeks of training cessation; and (6) HIIT-16, 10 weeks of HIIT followed by 6 weeks of training cessation. The training was performed 5 days/week. The subcutaneous adipose tissue (inguinal; SCAT), visceral adipose tissue (periuterine; VAT) and serum lipid profile were analysed after 10 or 16 weeks. Adipose tissue triglyceride lipase (ATGL) protein expression in VAT was assessed by western blotting.ResultsHIIT-10 and MICT-10 prevented the increase in SCAT, VAT and serum lipid levels seen in the CON group. During the 6-week detraining period, HIIT continued to prevent the increase in adipose tissue mass observed in the CON group, whereas MICT at least maintained this inhibition. The inhibition of fat mass increase was mainly the result of preventing adipocyte hypertrophy. The HIIT-10 and HIIT-16 groups showed the highest ATGL protein expression.ConclusionsHIIT has a comparable effect to MICT on inhibiting fat accumulation in female rats; however, the inhibition of SCAT and VAT increase by HIIT is superior to MICT after short-term training cessation.Graphical

Neuroendocrinological and Clinical Aspects of Leptin.

Obesity is characterized by an abnormal increase in adipose tissue mass and is regarded as a neurobehavioral as well as a metabolic disorder. Increases in body fat are caused by even slight, long-term discrepancies between energy intake and energy expenditure. It is a chronic condition linked to the metabolic syndrome, a spectrum of risky conditions, such as diabetes, high blood pressure, and heart disease. With a swiftly rising prevalence, obesity has emerged as a significant global health concern. Leptin influences the brain's neuroendocrine and metabolic processes, which is important for maintaining energy homeostasis. White adipose tissue secretes the majority of leptin, and there is a positive correlation between leptin levels in the blood and body fat percentages. The central nervous system is also modulated by leptin levels to modify energy intake and usage. The idea of an obesity cure sparked excitement after it was discovered more than 25 years ago. However, the leptin medication only effectively reduces weight in patients with congenital leptin insufficiency and not in patients with typical obesity who may also have leptin resistance. Recent research has focused on the role of leptin in managing weight reduction and preventing "yo-yo dieting". This review concentrates on the neurological effects of leptin with a focus on therapeutic and diagnostic applications, particularly for childhood obesity.

Development of Multi-particulate Formulation of Glabridin with L-Phenylalanine and Its Pre-clinical Evaluation for Anti-obesity Activity

Obesity is a chronic condition that is defined by pathophysiological mechanisms that lead to an increase in adipose tissue mass as a result of positive energy balance. Obesity is a multi-factorial disorder involving different mechanisms of action like humoral and neurogenic actions. Hypertrophied and hyperplastic adipocytes are indicative of pathological obesity. In the current treatment regimen, the drugs used mainly focus on a single mechanism of action. Herbal medicines are reported to have anti-obesity activity but due to the presence of multiple phytoconstituents its very difficult for one to finalize the dose and issue of palatability. So the best solution is to focus on usage of active phytoconstituent as an anti-obesity medicine. A high protein diet proved to have anti-obesity activity, the main constituent responsible for this activity is L-phenylalanine which is an essential amino acid that produces its activity by stimulating the satiety centre and thus decreases food intake. In this study, we are combining glabridin from Glycyrrhiza glabra and L-phenylalanine as both show anti-obesity activity through different action mechanisms, which may result in synergism. The study aims to prepare multi-particulate system (granules) of glabridin with L-phenylalanine and evaluate their anti-obesity and hypo-lipidemic action in HFD-treated rats.

Long-term depot specific changes in adipose tissue after treatment of acromegaly.

Patients with active acromegaly present a decreased adipose tissue (AT) mass, and short-term studies show that treatment leads to AT depot-specific gain. However, it remains unclear if the increase is persistent in the long-term perspective and/or is sex-dependent. To characterize the depot-specific changes of AT after treatment of acromegaly and identify contributing factors. Adipose tissue, including visceral (VAT), subcutaneous (SAT), and total (TAT), and android to gynoid ratio (A/G ratio) were measured by dual energy X-ray absorptiometry at diagnosis (n = 62), and after treatment at short-term (median (IQR) 1.9 (1.5-2.3)) and long-term 5.5 (3.9-9.5) years, and correlated to clinical and biochemical measurements. Growth hormone (GH), insulin-like growth factor 1 (IGF-1), glucose and HbA1c levels, gonadal status, and the presence of diabetes mellitus were recorded. Remission status was assessed at the long-term visit (IGF-1/ULN ≤ 1.3). Differences in the temporal course of AT from baseline to short- and long-term follow-up according to sex, diabetes, gonadal, and remission status were evaluated by mixed model analysis, adjusted for age. Despite a stable body mass index, VAT and A/G ratio increased at both time points, whereas SAT mainly increased at short-term, plateauing afterwards (P < .05 for all). Visceral adipose tissue and A/G ratio were higher in men (P = .035 and P < .001), and the A/G ratio increased more than in women (P = .003). Glucose and HbA1c decreased short-term (P < .05) and remained stable at long-term. The increase in AT depots correlated with the decrease of disease activity at long-term. Remission status had no effect on changes in AT mass during follow-up. Treatment of acromegaly leads to an increase in AT mass in a depot- and sex-specific manner both at short-term and long-term follow-up. Glucose metabolism improves rapidly after disease control and persists.

Abstract 19080: The Ketogenic Diet Aggravates the Ischemic Response in Mouse Hearts

Ketone bodies, particularly beta-hydroxybutyrate (B-OHB), have been identified as an important fuel source during physiological and pathological stress. Although controversial, consumption of a ketogenic diet (KD) may be used as a method to increase B-OHB availability. Since the KD is a high-fat, low carbohydrate diet, the diet may have harmful effects on the heart especially during ischemic injury. Therefore, the objective of this study was to investigate the effects of short- term consumption of the KD on cardiac ischemia-reperfusion injury. Male (n=14) and female (n=13) were randomly assigned to KD (90% calories from fat) or normal chow diet. Serum B-OHB and cholesterol were significantly higher in both male and females fed the KD. KD did not increase body weight in male and female mice but significantly increased adipose tissue mass by 2.7 and 1.9 fold, respectively. KD increased hepatic triglyceride content in both males and females and increased cardiac triglycerides only in male mice. Cardiac function was assessed in isolated perfused hearts on a mixed substrate buffer consisting of 0.4mM fatty acids, 5.5mM glucose, 50uU/ml insulin, 1.2mM lactate, and 0.5mM B-OHB. Baseline function was monitored for 15 minutes followed by 18 minutes of global ischemia and 36 minutes of reperfusion. Baseline LV developed pressure (LVDevP) and heart rate (HR) were not affected by the KD in either male or female mice. During ischemia, the end diastolic pressure (EDP) was significantly higher in both male and female KD hearts. Time to peak contracture was accelerated in male and female KD hearts (P&lt;0.05 vs chow), with a delay in female hearts (13.12 ± 1.06 vs. 9.27 ± 0.80 min, P&lt;0.05 vs KD male). At the end of reperfusion, rate pressure product (RPP, the product of LVDevP and HR) was lower in male KD vs male chow (P&lt;0.05) whereas RPP was similar in female KD and female chow. Moreover, RPP in female KD was significantly higher than male KD (6190 ± 929 vs 2133 ± 533 mmHg/min). These findings suggest that the KD may increase vulnerability of the heart to ischemia and may reduce recovery from ischemia, particularly in males. Overall, this study highlights potential sex differences and negative consequences of short-term consumption of the KD.

Fluid-Dependent Single-Frequency Bioelectrical Impedance Fat Mass Estimates Compared to Digital Imaging and Dual X-ray Absorptiometry

The need for a practical method for routine determination of body fat has progressed from body mass index (BMI) to bioelectrical impedance analysis (BIA) and smartphone two-dimensional imaging. We determined agreement in fat mass (FM) estimated with 50 kHz BIA and smartphone single lateral standing digital image (SLSDI) compared to dual X-ray absorptiometry (DXA) in 188 healthy adults (69 females and 119 males). BIA underestimated (p &lt; 0.0001) FM, whereas SLSDI FM estimates were not different from DXA values. Based on limited observations that BIA overestimated fat-free mass (FFM) in obese adults, we tested the hypothesis that expansion of the extracellular water (ECW), expressed as ECW to intracellular water (ECW/ICW), results in underestimation of BIA-dependent FM. Using a general criterion of BMI &gt; 25 kg/m2, 54 male rugby players, compared to 40 male non-rugby players, had greater (p &lt; 0.001) BMI and FFM but less (p &lt; 0.001) FM and ECW/ICW. BIA underestimated (p &lt; 0.001) FM in the non-rugby men, but SLSDI and DXA FM estimates were not different in both groups. This finding is consistent with the expansion of ECW in individuals with excess body fat due to increased adipose tissue mass and its water content. Unlike SLSDI, 50 kHz BIA predictions of FM are affected by an increased ECW/ICW associated with greater adipose tissue. These findings demonstrate the validity, practicality, and convenience of smartphone SLSDI to estimate FM, seemingly not influenced by variable hydration states, for healthcare providers in clinical and field settings.

THU067 Long-term Depot Specific Changes In Adipose Tissue After Treatment Of Acromegaly

Abstract Disclosure: C.M. Falch: Speaker; Self; Pfizer, Inc. K. Godang: None. T. Lekva: None. A. Heck: Speaker; Self; Ipsen, Recordati. J. Bollerslev: Advisory Board Member; Self; Pfizer, Inc. Speaker; Self; Ipsen, Pfizer, Inc. N.C. Olarescu: Speaker; Self; Pfizer, Inc., CORE2ED. Objective: Patients with active acromegaly present a decreased adipose tissue (AT) mass, and short-term studies show that the AT increases following treatment. However, it remains unclear if the increase is persistent in the long-term perspective. Aim: To characterize the depot specific changes of AT after treatment of acromegaly and identify contributing factors. Methods: In a clinically well-defined cohort of patients with acromegaly (n = 62), visceral (VAT), subcutaneous (SAT), total (TAT) adipose tissue, and android to gynoid ratio (A/G ratio) were measured by Dual Energy X-ray Absorptiometry (DXA). Measurements were assessed at diagnosis, and at a short- and long-term visit (median follow-up time (IQR): 1.9 (1.5-2.3) and 5.5 (3.6-9.6) years, respectively). Growth hormone (GH), insulin-like growth factor I (IGF-I), glucose and HbA1c levels, gonadal status, and the presence of diabetes mellitus were recorded prospectively. Remission status was assessed at the long-term visit (IGF-I ≤ 1.3 x ULN). Comparison between time points was performed using paired t-test or Mann-Whitney U test depending on distribution, and chi-square test for categorical variables. Differences in the temporal course were evaluated by mixed model analyses, adjusted for age. Results: VAT and A/G ratio increased at both time points, whereas SAT and TAT mainly increased at short-term, plateauing afterwards (p &amp;lt; 0.05 for all). VAT and A/G ratio were higher in men (p = 0.035 and p &amp;lt; 0.001), and the A/G ratio increased more compared to women (p = 0.003). BMI remained stable. Glucose and HbA1c decreased at short-term (p &amp;lt; 0.05) and remained stable at long-term, with no obvious sex differences. The gonadal status had no effect on the increase in AT in women. The increase in VAT (p = 0.046), but not SAT, TAT or A/G ratio, was more pronounced in patients with diabetes mellitus. The increase in AT strongly correlated with the decrease in GH (SAT (R = -0.48), TAT (R = -0.51), p &amp;lt; 0.001 for both) and IGF-I (VAT (R = -0.28, p = 0.036), SAT (R = -0.27, p = 0.046), TAT (R = -0.26, p = 0.048) at long-term. The decrease in glucose correlated with the decrease in HbA1c (R = 0.38, p = 0.009) and IGF-I (R = 0.32, p = 0.014) at long-term. Remission status had no effect on changes in AT mass during follow-up. Conclusion: Treatment of acromegaly leads to an increase in AT mass in a depot and sex specific manner both at short-term and long-term follow-up. Glucose metabolism improves rapidly after disease control and persists, whereas patients with diabetes mellitus have a higher VAT increase that may worsen their long-term metabolic outcome. Presentation: Thursday, June 15, 2023

SAT033 Disruption Of GHR In “Middle Aged” Mice Enhances Insulin Sensitivity And Extends Male Lifespan

Abstract Disclosure: S. Duran-Ortiz: None. E.O. List: None. J.A. Young: None. S.C. Mathes: None. R. Basu: None. Y.B. Slama: None. D.E. Berryman: None. Reduced growth hormone (GH) action has been shown to extend healthspan and lifespan in several organisms. In fact, mice and humans with a congenital disruption in the GH receptor (R) gene (GHRKO mice and patients with Laron Syndrome, respectively) have improved insulin sensitivity and are resistant to diabetes, cancer and age-associated cognitive decline. Importantly, the GHRKO mice hold the record for the longest-lived laboratory mice, with a lifespan one week shy of five years of age. GHRKO mice also show reduced markers of aging such as adipose tissue senescence and mTORC1 signaling in liver, kidney, heart and muscle. However, as GH action is required for normal growth and development, we and others have hypothesized that targeted inhibition of GH action at an adult age could be a potent method to extend healthy lifespan. To test this hypothesis and to elucidate how far in development would disruption of GHR extend healthy lifespan, our laboratory recently reported on two mouse lines with post-natal ablation of the GHR at a pubertal age (1.5 months - 1.5mGHRKO mice) and at mature-adult age (6 months - 6mGHRKO mice). We found that ablation of the GHR gene at both 1.5- and 6-months of age extends maximal and mean lifespan preferentially in females. Furthermore, 6mGHRKO mice showed improved oxidative stress resistance while males had improved insulin sensitivity and reduced cancer incidence. With these promising results, we believe that interventions to extend aging should be effective when administered later in life. In the current study, we disrupted the GHR in middle aged mice (12 months - 12mGHRKO mice) using the Cre-Lox system. We found that 12mGHRKO mice exhibit GH insensitivity (high serum GH and low IGF-1 levels), increased adipose tissue mass, reduced lean mass, minimal impact on body weight and length, improved insulin sensitivity and reduced glucose levels in males as well as decreased adipose tissue fibrosis in females compared to males. Moreover, despite the increased fat mass, motor coordination and strength as measured by rotarod and grip strength tests show no deficit in 12mGHRKO mice compared to the controls. Importantly, the male 12mGHRKO mice showed a preferential and significant lifespan extension compared to control mice. Collectively, our results indicate that not only does post-natal GHR disruption does not affect growth and development, but it also confers several crucial healthspan and lifespan advantages. Acknowledgements: This work is supported by the State of Ohio's Eminent Scholar Program, by NIH grant AG059779, by the American Federation for Aging Research (AFAR) and by the Diabetes Institute and by the AMVETS. Presentation: Saturday, June 17, 2023

Profiling of Skeletal Muscle and Adipose Tissue Depots in Men with Advanced Prostate Cancer Receiving Different Forms of Androgen Deprivation Therapy

BackgroundAndrogen deprivation therapy (ADT) is a common treatment modality for men with prostate cancer. Increases in adipose tissue mass and decreases in skeletal muscle mass are known on-target adverse effects of standard ADT. The effects of newer agents such as abiraterone acetate (ABI) and enzalutamide (ENZA) on body composition and how these compare with standard luteinizing hormone-releasing hormone agonists (aLHRHs) are unclear. ObjectiveTo assess the effects of different forms of androgen deprivation therapy on body composition in men with prostate cancer. Design, setting, and participantsUsing a retrospective design, 229 patients receiving aLHRHs alone (n = 120) or in combination with ABI (n = 53) or ENZA (n = 56) were studied. Outcome measurements and statistical analysisMuscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at baseline, 6 mo, and 18 mo after initiating therapy using a cross-sectional densitometry analysis performed on standard of care computed tomography images. Response trajectories for all treatment groups were calculated via a two-way analysis of variance post hoc test, for both within-group and between-group differences. Results and limitationsTreatment with aLHRHs, ABI, and ENZA was associated with a median muscle volume loss of –1.4%, –4.8%, and –5.5% at 6 mo, and –7.1%, –8.1%, and –8.3% at 18 mo, respectively. Therapy with aLHRHs was associated with minimal changes in VAT (0.3% at 6 mo and –0.1% at 18 mo). ABI therapy was associated with significant increases in VAT at 6 mo (4.9%) but not at 18 mo (0.5%), and ENZA therapy was associated with significant decreases in VAT (–4.6% at 6 mo and –5.4% at 18 mo). With respect to SAT, treatment with aLHRHs was associated with increases over time (8.6% at 6 mo and 4.7% at 18 mo), ABI was associated with decreases over time (–3.6% at 6 mo and –6.8% at 18 mo), and ENZA had no clear effects (1.7% at 6 mo and 3.3% at 18 mo). ConclusionsADT regimens cause significant short-term losses in muscle mass, with the most rapid effects occurring with ABI and ENZA. The three regimens have disparate effects on SAT and VAT, suggesting distinct roles of androgens in these tissues. Patient summaryAndrogen deprivation therapy alters body composition in men with prostate cancer. Abiraterone and enzalutamide are associated with losses in muscle mass compared with luteinizing hormone-releasing hormone agonists. These treatments impact subcutaneous and visceral fat mass, suggesting distinct roles of androgens in these tissues.

Orlistat for obesity management with high levels of TNFα in children

Childhood obesity has increased significantly over the past four decades. Obesity is the leading cause of preventable death in the world. An excess of body fat or adiposity characterizes it. TNFα expression in adipose tissue increases during the development of obesity. With the magnitude of the risk caused by obesity, efforts must be carried out to overcome obesity. Orlistat is a drug approved for obesity treatment in adolescents and children by the FDA. The data collection method was collected from articles related to orlistat in obesity management with high levels of TNFα in children. The inclusion criteria were from original articles, case-control studies, and review papers on childhood obesity, TNFα, and orlistat. Orlistat is effective in obesity management with high levels of TNFα in children. Obesity is associated with low-level inflammatory processes in WAT. The increase in adipose tissue mass simultaneously activates inflammatory processes in WAT, located in the liver and immune cells. WAT is the source of several pro-inflammatory cytokines, mainly TNFα. The use of orlistat has been recognized as an effective way to lose weight in childhood obesity. Along with weight loss, a decrease in adipocytes reduces TNF α levels in children.

Functional state of the glutathione system in the adipose tissue of rats with metabolic syndrome

Aim: To study the functional state of the components of the glutathione-dependent antioxidant system in the adipose tissue of rats with experimental metabolic syndrome (MetS).Material and Methods. The MetS model was carried out on male Wistar rats using a high-fat, high-carbohydrate diet (HFHCD). Body and adipose tissue weight were measured. Blood serum levels of glucose, insulin, leptin, triacylglycerides and cholesterol were assessed. In epididymal adipose tissue the level of reactive oxygen species (ROS) was determined by fluorescent method. The concentration of reduced (GSH) and oxidized (GSSG) glutathione, activity of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase enzymes were assessed spectrophotometrically in epididymal adipose tissue.Results. It was found that HFHCD led to an increase in body weight, obesity, hyperglycemia, insulin resistance, dyslipidemia, and leptinemia in the experimental group rats. An increase in adipose tissue mass had a positive correlation with an increase in the concentration of glucose, serum leptin, and ROS levels in the epididymal adipose tissue of rats with MetS. It was found that the level of total glutathione in the adipose tissue of the experimental group rats decreased mainly due to a decrease in the level of GSH. The rats receiving HFHCD also showed a decrease in the activity of glutathione peroxidase and glutathione-S-transferase, but the activity of glutathione reductase increased.Conclusion. Obesity, as a key component of MetS, is a trigger of insulin resistance, chronic low-grade inflammation and oxidative stress. The study showed that the development of MetS and obesity in the experimental animal group is accompanied by a shift of adipocyte redox balance toward oxidative stress, which is expressed in a decrease of GSH/GSSG ratio and glutathione-dependent antiperoxide protection enzymes activity.

The Xanthine Oxidase Inhibitor Febuxostat Suppresses Adipogenesis and Activates Nrf2.

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical inducer of antioxidants, which is bound and repressed by a kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. The Keap1-Nrf2 axis appears to be a major mechanism for robust inducible antioxidant defenses. Here, we demonstrate that febuxostat, a xanthine oxidase inhibitor, alleviates the increase in adipose tissue mass in obese mouse models with a high-fat diet or ovariectomy. Febuxostat disrupts in vitro adipocytic differentiation in adipogenic media. Adipocytes appeared at day 7 in absence or presence of febuxostat were 160.8 ± 21.2 vs. 52.5 ± 12.7 (p &lt; 0.01) in 3T3-L1 cells, and 126.0 ± 18.7 vs. 55.3 ± 13.4 (p &lt; 0.01) in 10T1/2 cells, respectively. Adipocyte differentiation was further enhanced by the addition of hydrogen peroxide, which was also suppressed by febuxostat. Interestingly, febuxostat, but not allopurinol (another xanthine oxidase inhibitor), rapidly induced the nuclear translocation of Nrf2 and facilitated the degradation of Keap1, similar to the electrophilic Nrf2 activator omaveloxolone. These results suggest that febuxostat alleviates adipogenesis under oxidative conditions, at least in part by suppressing ROS production and Nrf2 activation. Regulation of adipocytic differentiation by febuxostat is expected to inhibit obesity due to menopause or overeating.

Thrombin-Mediated Formation of Globular Adiponectin Promotes an Increase in Adipose Tissue Mass.

A decrease in the circulating levels of adiponectin in obesity increases the risk of metabolic complications, but the role of globular adiponectin, a truncated form produced by proteolytic cleavage, has not been defined. The objective of this investigation was to determine how globular adiponectin is generated and to determine whether this process impacts obesity. The cleavage of recombinant full-length adiponectin into globular adiponectin by plasma in vitro was used to identify Gly-93 as the N-terminal residue after proteolytic processing. The amino acid sequence of the cleavage site suggested thrombin was the protease responsible for cleavage, and inhibitors confirmed its likely involvement. The proteolytic site was modified, and this thrombin-resistant mutant protein was infused for 4 weeks into obese adiponectin-knockout mice that had been on a high-fat diet for 8 weeks. The mutation of the cleavage site ensured that globular adiponectin was not generated, and thus did not confound the actions of the full-length adiponectin. Mice infused with the mutant adiponectin accumulated less fat and had smaller adipocytes compared to mice treated with globular adiponectin, and concurrently had elevated fasting glucose. The data demonstrate that generation of globular adiponectin through the action of thrombin increases both adipose tissue mass and adipocyte size, but it has no effect on fasting glucose levels in the context of obesity.

Sodium-to-Potassium Ratio as an Indicator of Diet Quality in Healthy Pregnant Women

This study aimed to investigate diet quality in healthy pregnant women based on the Na-to-K ratio from 24 h urine sample and food frequency questionnaire (FFQ), to compare dietary micro- and macronutrient intake with current nutritional recommendations (RDA), and to investigate whether gestational weight gain (GWG) is associated with Na-to-K ratio and diet quality during pregnancy in general. Sixty-four healthy pregnant women between 37 and 40 weeks of gestation participated in the study. Participants' GWG, body composition, molar 24 h urine Na-to-K ratio, and FFQ data on average daily total energy, food groups, and micro-/macronutrient intake were obtained. A Na-to-K ratio of 2.68 (1.11-5.24) does not meet nutrition quality and is higher than the WHO recommendations due to excessive sodium and insufficient potassium intake. FFQ Na-to-K ratio was associated with a higher daily intake of soups, sauces, cereals, fats, and oils and a low intake of fruit and non-alcoholic beverages. A total of 49% of pregnant women exhibited excessive GWG, which was attributed to the increase in adipose tissue mass. GWG was not associated with total energy but may be the result of insufficient physical activity during pregnancy. Daily intake of vitamin D, vitamin E, folate, niacin, riboflavin, calcium, iron, and zinc was suboptimal compared to RDA.

Associations of GHR, IGF-1 and IGFBP-3 expression in adipose tissue cells with obesity-related alterations in corresponding circulating levels and adipose tissue function in children

Components of the growth hormone (GH) axis, such as insulin-like growth factor-1 (IGF-1), IGF-1 binding protein-3 (IGFBP-3), GH receptor (GHR) and GH-binding protein (GHBP) regulate growth and metabolic pathways. Using our Leipzig Adipose Tissue (AT) Childhood Cohort and Leipzig Atherobesity Childhood Cohort (n=306), we asked if serum levels of these factors are altered with overweight/obesity and if this is related to gene expression of these factors in AT cells and/or increased fat mass in childhood obesity. Furthermore, we hypothesized that gene expression of GHR, IGF-1 and IGFBP-3 in AT is associated with overweight/obesity and AT function in children. Serum GHBP levels were increased in children with overweight/obesity throughout childhood, while for IGF-1 levels and the IGF-1/IGFBP-3 molar ratio this obesity-related elevation was only detectable until early puberty. Circulating levels did not correlate with gene expression of these factors in AT cells, which was decreased with overweight/obesity. Independent from body mass index, gene expression of GHR, IGF-1 and IGFBP-3 in AT cells was related to parameters of AT dysfunction, such as adipocyte hypertrophy, and increased insulin levels. Serum GHBP was associated with the percentage of liver fat and transaminase levels. We conclude that the obesity-related elevations in serum GHBP and IGF-1 are unlikely to be caused by increased subcutaneous AT mass and elevations in serum GHBP are more closely related to liver status in children. The diminished gene expression of these factors in AT cells with childhood obesity may contribute to early AT dysfunction and a deterioration of the metabolic state.

First Testing of Literature-Based Models for Predicting Increase in Body Weight and Adipose Tissue Mass After Kidney Transplantation.

Introduction: Weight gain is a risk factor for poor clinical outcomes following kidney transplantation. Research Question: This study's aim was a first testing of 2 models to identify patients early after kidney transplantation who are at risk for weight gain and increase in adipose tissue mass in the first year after kidney transplantation. Design: The literature-based models were evaluated on longitudinal data of 88, respectively 79 kidney transplant recipients via ordinary and Firth regression, using gains ≥ 5% in weight and adipose tissue mass respectively as primary and secondary endpoints. Results: The models included physical activity, smoking cessation at time of kidney transplantation, self-reported health status, depressive symptomatology, gender, age, education, baseline body mass index and baseline trunk fat as predictors. Area under the curve was 0.797 (95%-CI 0.702 to 0.893) for the weight model and 0.767 (95%-CI 0.656 to 0.878) for the adipose tissue mass model-showing good, respectively fair discriminative ability. For weight gain ≥ 5%, main risk factors were smoking cessation at time of transplantation (OR 16.425, 95%-CI 1.737-155.288) and better self-reported baseline health state (OR 1.068 for each 1-unit increase, 95%-CI 1.012-1.128). For the adipose tissue mass gain ≥ 5%, main risk factor was overweight/obesity (BMI ≥ 25) at baseline (odds ratio 7.659, 95%-CI 1.789-32.789). Conclusions: The models have potential to assess patients' risk for weight or adipose tissue mass gain during the year after transplantation, but further testing is needed before implementation in clinical practice.

Prostaglandin D2 and F2α as Regulators of Adipogenesis and Obesity.

Prostaglandins (PGs) are lipid-derived autacoids that are synthesized from arachidonic acid by the action of cyclooxygenases and PG terminal synthases. PGs consist of PGD2, PGE2, PGF2α, prostacyclin (PGI2), and thromboxane A2, which act through G protein-coupled receptors. PGs sustain homeostatic functions and exert a variety of pathophysiological roles to regulate the development of various diseases such as obesity and dyslipidemia. Adipocytes (fat cells) have the unique capacity to accumulate large amounts of lipids as energy source in lipid droplets. Adipogenesis is the process of differentiation from preadipocytes to mature adipocytes, which is regulated by various adipogenic transcription factors. Obesity is defined as an abnormal increase in adipose tissue mass and is considered to be a risk factor for the development of lifestyle-related diseases including cardiovascular disease, hyperlipidemia, and type 2 diabetes mellitus. This review summarizes insights into the roles of PGD2, PGF2α, and their synthases in the regulation of adipogenesis and obesity.

Respiratory diseases and obesity: special phenotype or independent events: Review

A combination of factors, including Western European eating habits, physical inactivity and genetic predisposition, lead to a dramatic increase in adipose tissue mass. A special place is occupied by abdominal obesity, in which there is an accumulation of adipose tissue in the mesentery of the small intestine and the omentum. Developing in conditions of visceral obesity, insulin resistance, dyslipidemia and systemic inflammation are one of the key components of the pathogenesis of type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fatty liver and pancreas disease, polycystic ovary disease, some forms of cancer (breast cancer, endometrial cancer, colonic and direct intestines). At the same time, the pathogenetic role of adipose tissue is not limited to its participation in the formation of the cardiometabolic continuum and oncogenesis. The most important role of metabolically active fat in the pathogenesis of many respiratory diseases is known, including bronchial asthma, obstructive sleep apnea and pulmonary hypertension. This paper presents an overview of current data on immunological, pathophysiological and clinical features of the phenotype of the combination of respiratory diseases with overweight and obesity.

Age-related features of anthropometric and biochemical status of men from infertile couples

Introduction . The obesity seems to grow into a real pandemic. As one of the consequences of obesity we observe a significant increase of infertility in married couples, including male infertility. As the situation with male fertility continues to deteriorate, we consider further investigation of etiology and pathogenesis of male infertility important. Aim of the study was to investigate age-related anthropometric characteristics and metabolic status in men from infertile couples. Material and methods. 426 men from infertile couples were divided into 5 groups according to age: 1) &lt; 30 years old, 2) 30.0-34.9 years old, 3) 35.0-39,9 years old, 4) 40.0-44.9 years old, 5) ≥ 45 years old. We carried out anthropometric examination and biochemical blood analysis. Results. Within groups 2 to 4 we observed group-to- group consecutive increase in body weight, body mass index values, waist circumference and waist circumference to hip circumference values which are related to the increase of adipose tissue mass in the abdominal region. We also detected the increase of hyperglycemia occurrence. Higher values of the abovementioned anthropometric parameters were detected for the test subjects of the group 1 despite the younger age. We observed 60 and 40 % of upper and lower types of abdominal fat distribution respectively for the group 1 test subjects. Conclusions. Based on the anthropometric parameters we conclude that the infertility can be caused by negative influence of subcutaneous and visceral adipose tissue accumulation for the youngest test subjects (age &lt; 30 years). For the older test subjects, infertility results of the cumulative effect of abdominal obesity and other medical and social factors. Group 4 test subjects (age 40-45) exhibit the most frequent abdominal obesity and associated with metabolic status disorders.