Excessive Visceral Fat Accumulation Research Articles

The therapeutic effects of traditional Chinese medicine on insulin resistance in obese mice by modulating intestinal functions

IntroductionObesity, mainly caused by excessive accumulation of visceral fat, excessive fat metabolism will cause hormone secretion imbalance and inflammation and other diseases. is extremely detrimental to human health. Although many treatments are available for obesity, most treatments fail to exert a radical effect or are associated with several side effects. Traditional Chinese medicine (TCM) for regulating the intestinal flora, lipid content and inflammation is considered effective. Based on previous studies, Artemisia capillaris, Astragalus propinquus, Phellodendron amurense, Salvia miltiorrhiza, Poria cocos, and Anemarrhena asphodeloides were selected to prepare an innovative herbal formula. MethodsTCM was characterized by UHPLC-Q-Orbitrap-MS. The anti-inflammatory and lipid-lowering effects of the TCM formula prepared were evaluated in a high-fat diet-fed obese mouse model. The effects of the TCM formula on the intestinal flora were also investigated. ResultsWeights and insulin resistance, as well as inflammation, decreased in the mice after treatment. At the same time, lipid metabolism increased after the mice were gavaged with the TCM formula for 2 weeks. The intestinal motility of the drug administration group was enhanced, with partial restoration of the intestinal flora. ConclusionIn summary, our innovative Chinese herbal formula significantly reduced weight, reduced intestinal inflammation, improved intestinal motility, and improved lipid metabolism in obese mice. Furthermore, the innovative formula effectively prevented relevant obesity-induced metastatic diseases in the mice.

Interrelationships among accumulations of intra- and peri-organ fat, visceral fat, and subcutaneous fat.

We aimed to clarify the relationship between intra- and peri-organ fat, visceral fat, and subcutaneous fat. We used abdominal CT to evaluate intra- and peri-organ fat accumulations in the pancreas, liver, spleen, renal parenchyma, renal sinus, and skeletal muscle. The relationships between these fats, visceral fat, and subcutaneous fat were examined by using the partial correlation and covariance analysis, adjusting for BMI. We found that visceral fat and each intraand peri-organ fat accumulation were positively correlated, whereas subcutaneous fat and the accumulation of each intra- and peri-organ fat and visceral fat were negatively correlated. Pancreas fat, liver fat, renal sinus fat, and skeletal muscle fat accumulated significantly more in people with excessive visceral fat accumulation than in those without excessive visceral fat accumulation (p = 0.01, 0.006, 0.008, 0.02, respectively). In conclusion, intra- and peri-organ fat accumulation in each organ shows a positive correlation with visceral fat and a negative correlation with subcutaneous fat, independent of BMI.

Impact of surgical treatment on lipid metabolism in patients with lumbar spinal disorders: Prospective observational study

PurposeIt is still unclear how lumbar spinal surgery affects the lipid metabolism of patients with lumbar spinal disorders (LSDs) such as lumbar spinal canal stenosis and lumbar disk herniation. The present study aimed to assess the impact of lumbar spinal surgery on lipid metabolism in patients with LSDs and clarify the factors associated with changes in visceral fat (VF) accumulation before and after lumbar spinal surgery.MethodsConsecutive patients with lumbar spinal surgery for LSDs were prospectively included. Abdominal computed tomography images and blood examination of the participants were evaluated before surgery and at 6 months and 1 year after surgery. The cross-sectional VF area (VFA) was measured at the level of the navel using computed tomography images. Blood examination items included triglycerides and high-density lipoprotein (HDL).ResultsThe study enrolled a total of 138 patients. Female patients with LSDs had significantly increased VFA and serum triglyceride levels after lumbar spinal surgery. On multivariable analysis, the group with > 100 cm2 of preoperative VFA and a postoperative decrease in VFA had a significantly worse preoperative walking ability based on the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (relative risk 2.1; 95% confidence intervals 1.1–4.1).ConclusionsThe present study demonstrated that patients with LSDs did not necessarily improve their lipid metabolism after lumbar spinal surgery. Instead, female patients with LSDs had significantly deteriorated lipid metabolism after lumbar spinal surgery. Finally, a worse preoperative walking ability was associated with the improvement in excess VF accumulation after lumbar spinal surgery.

Pathophysiological significance in abdominal fat distribution in non-obese children with type 2 diabetes.

The aim of the study was to determine the pathogenesis of non-obese children with type 2 diabetes, and its relationship with fat distribution. The study participants included 36 obese children with type 2 diabetes (age: 13.5 years, BMI: 28.3, BMI percentile: 91.9) and 30 non-obese children with type 2 diabetes (age: 13.5 years, BMI: 23.1, BMI percentile: 74.0). The proportion of female participants was significantly higher in non-obese children than in obese children (73.3% vs. 41.7%, p < 0.001). Abdominal fat distribution, evaluated by subcutaneous fat (SF) area, visceral fat (VF) area, and the ratio of VF area to SF area (V/S ratio), measured using computed tomography, and serum lipid levels and liver function were compared between the two groups. Non-obese children with type 2 diabetes had significantly smaller SF area and also smaller VF area than obese children with type 2 diabetes (SF area: 158.3 m2 vs. 295.3 m2, p < 0.001, VF area: 71.0 m2 vs. 94.7 m2, p = 0.032). Whereas non-obese children with type 2 diabetes had significantly greater V/S ratio than obese children with type 2 diabetes (0.41 vs. 0.31, p = 0.007).The prevalence of dyslipidemia and liver dysfunction were similar in the two groups. In conclusion, non-obese children with type 2 diabetes had excess accumulation of VF despite a small amount of SF, which might be associated with glucose intolerance and other metabolic disorders.

De novo cholesterol biosynthesis: an additional therapeutic target for the treatment of postmenopausal breast cancer with excessive adipose tissue.

The onset and development of breast cancer in postmenopausal women are associated with closely related individual-dependent factors, including weight gain and high levels of circulating androgens. Adipose tissue is the most peripheral site of aromatase enzyme synthesis; therefore, the excessive accumulation of visceral fat results in increased androgens aromatization and estradiol production that provides the microenvironment favorable to tumorigenesis in mammary epithelial cells expressing estrogen receptors (ERs). Moreover, to meet the increased requirement of cholesterol for cell membrane assembly and the production of steroid hormones to sustain their proliferation, ER-positive cells activate de novo cholesterol biosynthesis and subsequent steroidogenesis. Several approaches have been followed to neutralize the de novo cholesterol synthesis, including specific enzyme inhibitors, statins, and, more recently, metformin. Cumulating evidence indicated that inhibiting cholesterol biosynthesis by statins and metformin may be a promising therapeutic strategy to block breast cancer progression. Unlike antiestrogens and aromatase inhibitors (AIs) which compete for binding to ER and inhibit androgens aromatization, respectively, statins block the production of mevalonic acid by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and metformin hampers the activation of the sterol regulatory element-binding protein 2 (SREBP2) transcription factor, thus inhibiting the synthesis of several enzymes involved in cholesterol biosynthesis. Noteworthy, statins and metformin not only improve the prognosis of overweight patients with ER-positive cancer but also improve the prognosis of patients with triple-negative breast cancer, the aggressive tumor subtype that lacks, at present, specific therapy.

Sarcopenia and excess visceral fat accumulation negatively affect early urinary function after I-125 low-dose-rate brachytherapy for localized prostate cancer.

To evaluate the effects of sarcopenia and excess visceral fat accumulation on early urinary function after I-125 low-dose-rate brachytherapy for prostate cancer. We retrospectively reviewed consecutive patients who underwent brachytherapy for prostate cancer. Pre-treatment computed tomography was used to measure skeletal muscle index at the L3 level to assess sarcopenia and visceral fat area at the umbilical level. The International Prostate Symptom Score and the University of California Los Angeles Prostate Cancer Index were used to assess quality of life during the 24months after brachytherapy. Logistic regression analysis was used to examine whether sarcopenia and excess visceral fat accumulation had clinically significant effects on post-treatment quality of life. Among 246 patients, 92 (37.4%) were stratified into the sarcopenia group and 141 (57.3%) into the excess visceral fat accumulation group. The sarcopenia group had significantly lower University of California Los Angeles Prostate Cancer Index urinary function than the non-sarcopenia group 24months post-brachytherapy. The excess visceral fat accumulation group had significantly poorer International Prostate Symptom Score total, storage, and voiding scores than the non-excess accumulation group 12months post-brachytherapy. In the multivariate analysis, sarcopenia had a clinically significant adverse effect on the University of California Los Angeles Prostate Cancer Index urinary function at 12months. Excess visceral fat accumulation had a clinically significant adverse effect on the International Prostate Symptom Score voiding and storage scores at 12months. Sarcopenia and excess visceral fat accumulation negatively affect urinary function early after I-125 low-dose-rate brachytherapy for prostate cancer.

PD38-05 EXCESSIVE VISCERAL FAT IN MEN IS ASSOCIATED WITH THE PRESENCE AND SEVERITY OF OVERACTIVE BLADDER

You have accessJournal of UrologyCME1 May 2022PD38-05 EXCESSIVE VISCERAL FAT IN MEN IS ASSOCIATED WITH THE PRESENCE AND SEVERITY OF OVERACTIVE BLADDER Tomohiro Matsuo, Yasuyoshi Miyata, Hidenori Ito, Hiroki Kurata, Masahito Masato, Kensuke Mitsunari, Kojiro Ohba, and Hideki Sakai Tomohiro MatsuoTomohiro Matsuo More articles by this author , Yasuyoshi MiyataYasuyoshi Miyata More articles by this author , Hidenori ItoHidenori Ito More articles by this author , Hiroki KurataHiroki Kurata More articles by this author , Masahito MasatoMasahito Masato More articles by this author , Kensuke MitsunariKensuke Mitsunari More articles by this author , Kojiro OhbaKojiro Ohba More articles by this author , and Hideki SakaiHideki Sakai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002596.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Increased abdominal visceral fat induces abnormal adipocytokine secretion. This leads to overproduction of various inflammatory cytokines, which induce systemic chronic inflammation and can result in metabolic syndrome (MetS). Although it is understood that systemic inflammation spread due to MetS can cause various lifestyle diseases, it was recently reported that MetS is also an important factor in lower urinary tract symptoms (LUTS), including overactive bladder (OAB). A recent study of women showed that excessive visceral fat accumulation, which triggers MetS, is related to OAB presence and severity. However, there has been no such research on men, who are considered more susceptible to the effects of visceral fat than women. Therefore, the objective of this study was to clarify the relationship between visceral fat volume and OAB in men. METHODS: Men who underwent abdominal CT as part of health checks and had not been treated for LUTS before the study were included. OAB was defined as scoring ≥2 points on question 3 (urinary urgency) of the Overactive Bladder Symptom Score (OABSS) and a total score of ≥3 points. Visceral fat area (VFA), visceral fat volume (VFV), and total abdominal fat volume (TAV) calculated from abdominal CT, the presence of OAB, associations between these fat parameters; and OABSS total score were examined. Visceral fat was measured using a 3-dimensional image analysis system (SYNOSE VINCENT®, FUJIFILM Corporation, Tokyo, Japan). RESULTS: There were 519 participants in the analysis set. The mean age was 57.4±15.2 years. There were 135 patients (26.0%) who met the criteria for OAB. From the abdominal CT results, the OAB group exhibited statistically and significantly higher values than the non-OAB group for the following factors: VFA (non-OAB; 72.1±39.6 cm2, OAB; 113.5±72.2 cm2, P<0.001), VFV (non-OAB; 1829.1±1249.6 cm3, OAB; 3299.6±2380.2 cm3, P<0.001), and VFV/TAV (non-OAB; 0.32±0.12, OAB; 0.50±0.15, P<0.001). When correlations between these factors obtained from the image findings and the OABSS total score were examined, VFV/TAV had the strongest correlation with the OABSS total score (r=0.511, P<0.001). The area under the receiver operating characteristic curve for the presence of OAB and VFV/TAV was 0.821. At a cutoff value of 0.409, the sensitivity and specificity were 0.741 and 0.732, respectively. Multivariate analysis of VFV/TAV and factors contributing to OAB, such as age, prostate volume, hypertension, and diabetes, showed that high VFV/TAV (≥0.409) was an independent risk factor for OAB in univariate and multivariate analyses (odds ratio 4.51, 95% confidence interval: 2.57-7.89, P<0.001). CONCLUSIONS: We found that VFA and increased VFA were closely associated with OAB presence and severity in men. The results also indicated that excessive abdominal visceral fat accumulation itself is an important risk factor for OAB. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e647 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomohiro Matsuo More articles by this author Yasuyoshi Miyata More articles by this author Hidenori Ito More articles by this author Hiroki Kurata More articles by this author Masahito Masato More articles by this author Kensuke Mitsunari More articles by this author Kojiro Ohba More articles by this author Hideki Sakai More articles by this author Expand All Advertisement PDF DownloadLoading ...

The role of adipokines in the development of adipose tissue dysfunction and other metabolic disorders

The role of specific adipokines in the formation of adipose tissue dysfunction is considered. Obesity is a multifactorial disease that is characterized by excessive adipose tissue accumulation in the body and is a risk factor for the development of several other diseases, including type 2 diabetes mellitus, cardiovascular diseases, and non-alcoholic fatty liver disease. Obesity is one of the main causes of chronic diseases and disability in modern society. Adipose tissue takes an active part in cellular reactions and metabolic homeostasis and does not represent inert tissue only for energy storage. In obesity, excessive accumulation of visceral fat causes adipose tissue dysfunction, which greatly contributes to the occurrence of concomitant diseases. Adipose tissue is capable of synthesizing and releasing a large number of hormones, cytokines, extracellular matrix proteins, growth factors, and vasoactive factors, which are collectively called adipokines, affecting various physiological and pathophysiological processes in the body. Perivascular adipose tissue produces cytokines that affect angiogenesis and peripheral vascular resistance. Adiponectin suppresses the production of glucose in the liver and enhances fatty acid oxidation in the skeletal muscles, which together contribute to a favorable metabolic effect in energy homeostasis, protect cells from apoptosis, and reduce inflammation in various cell types through receptor-dependent mechanisms. Leptin modulates vasoconstriction depending on sympathetic activity while resistin is involved in insulin resistance due to inflammation, wherein its high level determines metabolically unhealthy obesity. Additionally, visfatin plays an important role in the pathogenesis of vascular inflammation in obesity and diabetes mellitus while osteopontin regulates the production of inflammatory mediators by immune cells and omentin plays an important anti-inflammatory and insulin-sensitizing role. The production of most inflammatory mediators in adipose tissue dysfunction increases and contributes to the progression of obesity and related metabolic and vascular disorders. Considering adipokines as biological markers of pathological processes is necessary since their study will create prerequisites for preventive measures and will contribute to the positive treatment process.

The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium.

Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD.

Excessive accumulation of visceral fat is associated with lower urinary symptoms including overactive bladder in female patients.

ObjectiveTo assess the relationship between visceral fat accumulation and lower urinary tract symptoms in female patients.MethodsIn this single‐center study, we enrolled all women who underwent screening abdominal computed tomography 3 months before the study, irrespective of whether they experienced lower urinary tract symptoms. The Overactive Bladder Symptom Score was used to assess subjective symptoms. Uroflowmetry and ultrasound assessment of post‐void residual urine were carried out to assess objective signs. We analyzed the relationship between lower urinary tract symptoms and various body fat accumulation parameters, including visceral fat area, visceral fat volume and total abdominal fat volume, assessed using computed tomography scans.ResultsA total of 182 patients were divided into the overactive bladder (n = 71, 39.0%) and the non‐overactive bladder (n = 111, 61.0%) groups. The visceral fat area, visceral fat volume and visceral fat volume/total abdominal fat volume values were all significantly higher in the overactive bladder group than in the non‐overactive bladder group (P < 0.001). Of these parameters, the visceral fat volume/total abdominal fat volume ratio showed the strongest correlation with the total Overactive Bladder Symptom Score (r = 0.394, P < 0.001). The maximum urine flow rate correlated negatively with the visceral fat volume/total abdominal fat volume value (visceral fat volume/total abdominal fat volume r = –0.289, P < 0.001). Subsequent multivariate analysis showed that a high visceral fat volume/total abdominal fat volume value, age and metabolic syndrome‐related diseases were independent risk factors for the presence of overactive bladder.ConclusionsExcessive accumulation of visceral fat is independently associated with overactive bladder in females.

Abrogation of Toll-Like Receptor 4 Mitigates Obesity-Induced Oxidative Stress, Proinflammation, and Insulin Resistance Through Metabolic Reprogramming of Mitochondria in Adipose Tissue.

Aims: Obesity-induced excessive visceral fat (VF) accumulation is associated with insulin resistance (IR), systemic oxidative stress, and chronic inflammation. As toll-like receptor 4 (TLR4) plays an important role in innate immunity, we herein investigate the effect of TLR4 knockout (T4KO) in a high-fat high-sucrose diet (HFD)-induced obesity mouse model. Results: C57BL6 wild-type (WT) and T4KO mice were fed with either control diet (CD) or HFD for 12 months, rendering four experimental groups: WT+CD, WT+HFD, T4KO+CD, and T4KO+HFD. Compared with WT+CD, WT+HFD demonstrated significant increase in VF accumulation, oxidative damage, M1/M2 macrophage ratio, chronic inflammation, and development of IR. Compared with WT+HFD, T4KO+HFD presented increased BW and body fat with higher subcutaneous fat (SF)/VF ratio, but lower body temperature, as well as decreased oxidative damage, M1/M2 macrophage ratio, chronic inflammation, and IR. Unlike WT+HFD, T4KO+HFD exhibited an increase in mitochondrial electron transport chain activity but a decrease of uncoupling protein 2 (UCP2) level. While T4KO hindered HFD-induced increasing mitochondrial oxygen consumption rate, a shift toward a higher extracellular acidification rate in VF was observed. Notably, T4KO inhibits HFD-induced mitochondrial translocation of nuclear factor of activated T cells 2 (NFATC2), which contributed to mitochondrial metabolic reprogramming. Both fat distribution shifting from VF to SF and mitochondrial metabolic reprogramming may alleviate systemic oxidative stress and chronic inflammation. Innovation and Conclusion: Abrogation of TLR4 contributes to reduction of oxidative stress through metabolic reprogramming of mitochondria in VF, mitigating obesity-induced IR. The study provides critical insight into associating innate immunity-mitochondria interplay with prevention of diabetes.

O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity

Excessive visceral fat accumulation is a primary risk factor for metabolically unhealthy obesity and related diseases. The visceral fat is highly susceptible to the availability of external nutrients. Nutrient flux into the hexosamine biosynthetic pathway leads to protein posttranslational modification by O-linked β-N-acetylglucosamine (O-GlcNAc) moieties. O-GlcNAc transferase (OGT) is responsible for the addition of GlcNAc moieties to target proteins. Here, we report that inducible deletion of adipose OGT causes a rapid visceral fat loss by specifically promoting lipolysis in visceral fat. Mechanistically, visceral fat maintains a high level of O-GlcNAcylation during fasting. Loss of OGT decreases O-GlcNAcylation of lipid droplet-associated perilipin 1 (PLIN1), which leads to elevated PLIN1 phosphorylation and enhanced lipolysis. Moreover, adipose OGT overexpression inhibits lipolysis and promotes diet-induced obesity. These findings establish an essential role for OGT in adipose tissue homeostasis and indicate a unique potential for targeting O-GlcNAc signaling in the treatment of obesity.

Relevance of Leptin and Other Adipokines in Obesity-Associated Cardiovascular Risk.

Obesity, which is a worldwide epidemic, confers increased risk for multiple serious conditions including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue only for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins, and growth and vasoactive factors, which are collectively called adipokines known to influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. This review describes the relevance of specific adipokines in the obesity-associated cardiovascular disease.

Maternal exercise before and during pregnancy alleviates metabolic dysfunction associated with high-fat diet in pregnant mice, without significant changes in gut microbiota

Although maternal exercise before and during pregnancy is beneficial, the effects of exercise on microbiota changes during pregnancy are unknown. Here we tested the hypothesis that maternal exercise before and during pregnancy would positively affect glucose homeostasis, pancreatic cell function, and gut microbiota dysbiosis in high-fat diet (HFD) fed dams. Female C57BL/6 mice were fed either a HFD or a low-fat diet (LFD) for 12 weeks. The HFD mice were split into two groups for 4 weeks prior to pregnancy initiation and throughout the pregnancy: sedentary (HFD) or exercised (HFD + Ex). Food intake, body weight, body composition, and glucose and insulin tolerance were measured. At gestation day 19, blood, pancreas, gonadal visceral and subcutaneous fat, plantaris muscle, and cecum were collected for analysis. Both HFD and HFD + Ex mice had impaired glucose clearance compared to LFD mice at 15 days of gestation. No changes were found in pancreatic α- or β-cell health. HFD + Ex mice had significantly reduced visceral fat mass, serum insulin, and leptin levels and increased high-density lipoprotein levels, compared to HFD-fed mice. In contrast to our hypothesis, microbiota diversity and composition were not different among groups. The relative abundance of five bacterial phyla, such as Firmicutes, Bacteroidetes, Verrucomicrobia, Deferribacteres, and Actinobacteria, were not significantly altered with diet or exercise during pregnancy. Our findings suggest that maternal exercise prevents excess visceral fat accumulation, hyperinsulinemia, and hyperleptinemia associated with a HFD, but not through the alterations of gut microbiota composition or diversity during pregnancy.

Differences in Dietary Intake of Women with Standard Weight but Varying Body Fat Percentages in Japan

“Hidden obese people” have a high body fat percentage (BFP) despite having a normal BMI (18.5 &lt;BMI ? 25.0 BFP ?30) due to an excessive accumulation of visceral fat, which increases their risk of lifestyle-related diseases. We aimed to identify factors that contribute to hidden obesity among Japanese female students at the Nutritionist Training Facility University using their anthropomorphic measurements, lifestyle characteristics and nutritional intake. Characteristics of participants with hidden obesity physique (18.5 &lt;BMI ? 25.0 and BFP &gt;30%) (n = 160) and standard physique (18.5 &lt;BMI ? 25.0 and BFP &lt;30%) (n = 376) were compared using Student’s t-test or Welch’s t-test. The participants with hidden obesity physique have lower intake of energy (p = 0.044) and fat (p = 0.036) and a higher intake of carbohydrates (p = 0.023), cereals (p = 0.009) and sugary beverages (p = 0.020). This study suggests that a reduction in carbohydrate-dense foods is effective in preventing hidden obesity.

Dlk1 expression relates to visceral fat expansion and insulin resistance in male and female rats with postnatal catch-up growth.

Although prenatal and postnatal programming of metabolic diseases in adulthood is well established, the mechanisms underpinning metabolic programming are not. Dlk1, a key regulator of fetal development, inhibits adipocyte differentiation and restricts fetal growth. Assess DLk1 expression in a Wistar rat model of catch-up growth following intrauterine restriction. Dams fed ad libitum delivered control pups (C) and dams on a 50% calorie-restricted diet delivered pups with low birth weight (R). Restricted offspring fed a standard rat chow showed catch-up growth (R/C) but those kept on a calorie-restricted diet did not (R/R). Decreased Dlk1 expression was observed in adipose tissue and skeletal muscle of R/C pups along with excessive visceral fat accumulation, decreased circulating adiponectin, increased triglycerides and HOMA-IR (from p < 0.05 to p < 0.0001). Moreover, in R/C pups the reduced Dlk1 expression in adipose tissue and skeletal muscle correlated with visceral fat (r = -0.820, p < 00001) and HOMA-IR (r = -0.745, p = 0.002). Decreased Dlk1 expression relates to visceral fat expansion and insulin resistance in a rat model of catch-up growth following prenatal growth restriction. Modulation of Dlk1 expression could be among the targets for the early prevention of fetal programming of adult metabolic disorders.

Chronic inflammation associated with obesity exacerbates bone loss in mice

Abstract Dysfunctional adipose tissue characterized by abnormal inflammatory cytokine production during obesity, is linked to several metabolic disorders including bone loss. An increase in bone fracture incidence due to increased rates of obesity is becoming a significant new health concern. However, it is still obscure whether obesity accelerates bone loss. Herein, we have investigated the systemic weight gain, cytokine production, bone turnover markers and femur bone micro-architecture in high-fat diet (HFD) fed obese mice. HFD mice exhibited excessive visceral fat accumulation (2.4 fold) in the peritoneal cavity and increased body weight (2.1 fold) compared to regular chow diet (RCD) fed mice. The serum levels of pro-inflammatory cytokine IL-6 was increased approximately 8-fold in HFD mice compared to RCD mice. The serum bone turnover marker, C-terminal telopeptides of collagen (CTx), was almost 2-fold higher in HFD mice compared to RCD mice. Further, radiological studies from micro computed tomography (micro-CT) of femur suggests that HFD mice exhibited considerably reduced bone volume fraction (BV/TV) and cortical thickness compared to RCD mice. These results suggest the chronic inflammation associated with many metabolic disorders such as obesity may accelerate bone loss.

Efficacy and Safety of Lipase Inhibitor Orlistat in Japanese with Excessive Visceral Fat Accumulation: 24-Week, Double-Blind, Randomized, Placebo-Controlled Study.

IntroductionOrlistat is an inhibitor of pancreatic lipase and is used as an anti-obesity drug in many countries. However, there are no data available regarding the effects of orlistat on visceral fat accumulation in Japanese subjects. Therefore, this comparative, placebo-controlled, double-blind, randomized study aimed to evaluate the efficacy and safety of orlistat in Japanese participants with excessive visceral fat accumulation and without dyslipidemia, diabetes mellitus, and hypertension (“metabolic diseases”).MethodsThe study population included Japanese participants with excessive visceral fat accumulation (waist circumference ≥ 85 cm in males and ≥ 90 cm in females, which corresponds to a visceral fat area of 100 cm2) and without metabolic diseases. Following a 12-week observation term, participants were randomized to the orlistat 60 mg group (n = 100) or placebo group (n = 100). Both drugs were administered orally three times daily for 24 weeks. Participants were also counseled to improve their diet and to maintain exercise throughout the study. Visceral fat area, subcutaneous fat area, waist circumference, body weight, body mass index, adverse reactions, laboratory tests, and blood pressure were regularly assessed.ResultsVisceral fat area, waist circumference, and body weight were significantly reduced in the orlistat group (mean ± standard error, − 13.50 ± 1.52%, − 2.51 ± 0.25%, and − 2.79 ± 0.30%, respectively) compared to the placebo group (− 5.45 ± 1.50%, − 1.55 ± 0.26%, and − 1.22 ± 0.28%, respectively) at the last assessment. The main adverse reactions were defecation-related symptoms including oily spotting and flatus with discharge, resulting from the pharmacological effects of orlistat. Most adverse reactions were mild, and none were serious or severe.ConclusionOrlistat administration reduced visceral fat area, waist circumference, and body weight in Japanese participants with excessive visceral fat and without metabolic diseases. In addition, safety was confirmed with a tolerable profile. Orlistat may be useful to reduce excessive visceral fat accumulation when used in combination with diet and exercise.Trial RegistrationJapan Pharmaceutical Information Center identifier, JapicCTI-184005.FundingTaisho Pharmaceutical Co., Ltd.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-018-0835-5) contains supplementary material, which is available to authorized users.

Circadian rhythms of hormone secretion and obesity.

The adipose tissue homeostasis is profoundly affected by circadian rhythms of corticosteroid secretion and chronic loss of hormonal oscillations is associated with obesity. How adipose tissue differentially responds to pulsatile vs continuous presence of glucocorticoids is poorly defined. To address this question, Bahrami-Nejad et al studied differentiation of pre-adipocytes, containing endogenously tagged CCAAT/enhancer binding protein and peroxisome proliferator-activated receptor (PPAR) γ (key regulators of adipocyte differentiation), in response to corticosteroids that were delivered either in an oscillatory fashion or continuously. The authors show that the bi-stable state of differentiation of pre-adipocytes and adipocytes was regulated by a combination of fast and slow positive feedback networks, that determined unique threshold of PPARγ in these cells. Evidently, pre-adipocytes used the fast feedback loop to reject differentiation cues of oscillating pulses of glucocorticoids and failed to differentiate into fat cells. In contrast, when glucocorticoids were delivered continuously, precursor cells exploited the slow feedback loop to embark on a path of maximal differentiation. This differential differentiation response of pre-adipocytes to pulsatile vs continuous exposure to glucocorticoids was corroborated in vivo. Thus, mice receiving non-oscillating doses of exogenous glucocorticoids, for 21 d, elicited excessive accumulation of visceral and subcutaneous fat. These data shed new light on the mechanisms of obesity caused by putative misalignment of circadian secretion of glucocorticoids or their persistently high levels due to chronic stress or Cushing’s disease.

Potential adverse effects of botanical supplementation in high-fat-fed female mice

BackgroundInsulin resistance underlies metabolic syndrome and is associated with excess adiposity and visceral fat accumulation, which is more frequently observed in males than females. However, in young females, the prevalence of metabolic syndrome is rising, mainly driven by accumulation of abdominal visceral fat. The degree to which sex-related differences could influence the development of insulin resistance remains unclear, and studies of potential therapeutic strategies to combat metabolic syndrome using rodent models have focused predominantly on males. We therefore evaluated the effects of two nutritional supplements derived from botanical sources, an extract of Artemisia dracunculus L. (termed PMI5011) and Momordica charantia (commonly known as bitter melon), on female mice challenged with a high-fat diet in order to determine if dietary intake of these supplements could ameliorate obesity-induced insulin resistance and metabolic inflexibility in skeletal muscle.MethodsBody composition, physical activity and energy expenditure, fatty acid oxidation, insulin signaling, and gene and protein expression of factors controlling lipid metabolism and ectopic lipid accumulation were evaluated in female mice fed a high-fat diet supplemented with either PMI5011 or bitter melon. Statistical significance was assessed by unpaired two-tailed t test and repeated measures ANOVA.ResultsPMI5011 supplementation resulted in increased body weight and adiposity, while bitter melon did not induce changes in these parameters. Pyruvate tolerance testing indicated that both supplements increased hepatic glucose production. Both supplements induced a significant suppression in fatty acid oxidation in skeletal muscle homogenates treated with pyruvate, indicating enhanced metabolic flexibility. PMI5011 reduced lipid accumulation in skeletal muscle, while bitter melon induced a downward trend in lipid accumulation in the skeletal muscle and liver. This was accompanied by transcriptional regulation of autophagic genes by bitter melon in the liver.ConclusionsData from the current study indicates that dietary supplementation with PMI5011 and bitter melon evokes a divergent, and generally less favorable, set of metabolic responses in female mice compared to effects previously observed in males. Our findings underscore the importance of considering sex-related variations in responses to dietary supplementation aimed at combating metabolic syndrome.