Subcutaneous Adipose Tissue Mass Research Articles

The influence of a human macronutrient-matched diet on phenotypes in old mice.

Preclinical rodent models are essential research tools for improving understanding of physiological aging processes in humans. However, the translatability of findings obtained leveraging rodent models to humans is limited, likely due in part to differences in macronutrient composition of the diets. Here, we investigated the impact of a 3-month diet intervention in old male C57BL/6JN mice in which the macronutrient composition was aligned with that of a midlife/older adult in the United States, compared to a traditional rodent diet, and assessed various phenotypes that are typically altered with aging. Following the diet period, mice fed the human macronutrient-matched diet had greater quadricep and subcutaneous adipose and visceral adipose tissue masses compared to animals fed a traditional mouse diet. Frailty, assessed using a clinical frailty index, was lower, while grip strength was higher in mice fed the human-matched diet. Circulating metabolite and inflammatory cytokine profiles were altered in mice fed the human-matched diet. Notably, mortality rate (assessed in animals who died or were euthanized per veterinary recommendation before the pre-determined end of study euthanasia), tended to be lower in mice fed the human-matched diet. The present study underscores the importance of diet in rodent studies of aging, as differences in macronutrient composition can affect various physiological processes in old mice that are relevant to aging research.

Associations of Urinary Cadmium with Body Composition and Fat Distribution in US Adults: Findings from NHANES 2011-2018.

The effects of cadmium (Cd) on metabolic physiology remain controversial. Given the varying metabolic impacts associated with different body compositions, investigating the relationship between Cd exposure and body composition may facilitate further research. Here, the associations of body composition and fat distribution with urine Cd (UCd) were evaluated. This analysis included 2979 adult participants from the 2011-2018 National Health and Demographic Survey (NHANES). UCd was measured using inductively coupled plasma mass spectrometry and adjusted for urinary creatinine. Body composition and fat distribution were estimated using dual-energy x-ray absorptiometry (DXA). The study results show that UCd was negatively associated with fat mass index (FMI) and percent fat mass (p for trend < 0.001), and the negative correlation between UCd and FMI was stronger in males and smokers (all p for interaction < 0.05). In terms of abdominal fat distribution, UCd was negatively associated with abdominal subcutaneous adipose tissue (SAT) mass (p for trend < 0.001), but with abdominal visceral adipose tissue (VAT) mass only in those with low percent fat mass (< 32.3%) (p for trend = 0.026 and p for interaction < 0.05). UCd was positively related to percent VAT (p for trend < 0.001) and visceral-to-subcutaneous (VAT/SAT) ratio (p for trend = 0.003). And there was a significant negative association between UCd and android-to-gynoid (A/G) ratio (p for trend = 0.001). Meanwhile, UCd was negatively correlated with fat-free mass index (FFMI) (p for trend < 0.001). And the negative correlation between UCd and FFMI was stronger in males, smokers, and individuals with < 32.3 percent fat mass (all p for interaction < 0.05). We found the association of UCd with body composition and fat distribution, with distinct patterns observed in different demographic groups. These findings underscore the importance of considering UCd exposure in the context of body composition and fat distribution.

Nutrition, Growth, and Age at Puberty in Heifers

Puberty onset and age at first calving have a critical impact on livestock production for good reproductive efficiency of the herd and to reduce the duration of the non-productive stage of the growing heifer. Besides genetic factors, sexual maturation is also affected by environmental factors, such as nutrition, which can account for up to 20% of the observed variability. The rate of body weight gain during growth is considered the main variable influencing the age at puberty, dependent on planes of nutrition in growing animals during the prepubertal-to-pregnancy stage. This paper reviews current knowledge concerning nutrition management and attainment of puberty in heifers, considering the relevance of some indicators such as body measurements and hormones strictly linked to the growth and puberty process. Puberty onset is dependent on the acquisition of adequate subcutaneous adipose tissue mass, as it is the main source of the hormone leptin. Until a certain level, body condition score and age at puberty are negatively correlated, but beyond that, for fatter animals, such correlation is gradually lost. Age at puberty in heifers was reported to be negatively related to IGF-1. Future research should be planned considering the need to standardize the experimental animals and conditions.

Comparable glucagon-stimulated amino acid suppression in individuals with and without hepatic steatosis or steatohepatitis.

Hepatic amino acid (AA) metabolism and glucagon secretion are linked in a feedback cycle in which circulating AAs stimulate glucagon secretion, while glucagon stimulates hepatic AA catabolism. It has been proposed that metabolic dysfunction-associated steatotic liver disease (MASLD) leads to hepatic glucagon resistance, which may result in hyperaminoacidemia and hyperglucagonemia. We tested the glucagon effect on AA metabolism in subjects with obesity; 11 with steatohepatitis (MASH), 10 with steatosis (MAS), and seven subjects (CON) without steatosis. We performed a somatostatin clamp with infusions of insulin and low-dose followed by high-dose glucagon. We measured plasma levels of 17 AAs and assessed hepatic fat content (FF%) and body fat distribution (visceral and subcutaneous adipose tissue mass) by MRI. HighGlucagon suppressed plasma total AA equally in all groups; MASH 13% (SD 9%), MAS 14% (7%), CON 11% (5%), respectively. In univariate regression analyses visceral adipose tissue mass (β = 0.471, P = 0.011) and AA concentration at LowGlucagon (β = ─0.524, P = 0.004), but not FF% (β = ─0.243, P = 0.213), were significant predictors of AA reduction. Using a stepwise backward multiple regression approach revealed similar results. Total and specific AA levels (glutamic acid, tyrosine) were higher in both MASLD groups during the study and FF% was positively correlated to a number of individual AAs. Though finding elevated AA concentrations in subjects with MASLD, we conclude that in MASLD patients that do not have elevated glucagon at baseline, glucagon suppresses circulating AA levels equally in subjects with and without MASLD. NCT04042142.

The different association between fat mass distribution and intake of three major nutrients in pre- and postmenopausal women.

Obesity, characterized by excessive body fat accumulation, is associated with various chronic health conditions. Body fat plays a crucial role in health outcomes, and nutrient intake is a contributing factor. Menopause further influences body fat, but the precise relationships between nutrients and fat mass distribution in pre- and post-menopausal women are unclear. Data from 4751 adult women aged ≥18 years old (3855 pre-menopausal, 896 post-menopausal) with completed information were obtained from the National Health and Examination Survey (NHANES) from 2011 to 2018. Multivariate linear regression models were used to examine the associations between protein, carbohydrate, fat intake and total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android to gynoid ratio (A/G), subcutaneous adipose tissue mass (SAT), visceral adipose tissue mass (VAT). Subgroup analyses, stratified by menopausal status, were also conducted. Additionally, we employed smoothing curve fitting techniques to investigate potential non-linear relationships between fat mass distribution and nutrient intake. Compared with pre-menopausal women, post-menopausal women had higher body fat, BMI, and metabolic indicators but lower nutrient intake (All p<0.05). In the overall analysis, we found significant correlations between nutrient intake and fat mass. Specifically, protein intake was negatively correlated with TPF (β = -0.017, 95% CI: -0.030, -0.005), APF (β = -0.028, 95% CI: -0.044, -0.012), GPF (β = -0.019, 95% CI: -0.030, -0.008), while fat intake showed positive correlations with these measures (SAT: β = 2.769, 95% CI: 0.860, 4.678). Carbohydrate intake exhibited mixed associations. Notably, body fat mass-nutrient intake correlations differed by menopausal status. Generally speaking, protein intake showed negative correlations with body fat distribution in pre-menopausal women but positive correlations in post-menopausal women. Carbohydrate intake revealed significant negative associations with abdominal and visceral fat in post-menopausal women, while fat intake was consistently positive across all fat distribution indices, especially impacting visceral fat in post-menopausal women. Dietary intake plays a crucial role in body fat distribution, with menopausal status significantly influencing the impact of nutrients on specific fat distribution metrics. The study emphasizes the need for dietary guidelines to consider the nutritional needs and health challenges unique to women at different life stages, particularly concerning menopausal status, to effectively manage obesity.

Caloric restriction mitigates age-associated senescence characteristics in subcutaneous adipose tissue-derived stem cells.

Adipose tissue regulates metabolic balance, but aging disrupts it, shifting fat from insulin-sensitive subcutaneous to insulin-resistant visceral depots, impacting overall metabolic health. Adipose-derived stem cells (ASCs) are crucial for tissue regeneration, but aging diminishes their stemness and regeneration potential. Our findings reveal that aging is associated with a decrease in subcutaneous adipose tissue mass and an increase in the visceral fat depots mass. Aging is associated with increase in adipose tissue fibrosis but no significant change in adipocyte size was observed with age. Long term caloric restriction failed to prevent fibrotic changes but resulted in significant decrease in adipocytes size. Aged subcutaneous ASCs displayed an increased production of ROS. Using mitochondrial membrane activity as an indicator of stem cell quiescence and senescence, we observed a significant decrease in quiescence ASCs with age exclusively in subcutaneous adipose depot. In addition, aged subcutaneous adipose tissue accumulated more senescent ASCs having defective autophagy activity. However, long-term caloric restriction leads to a reduction in mitochondrial activity in ASCs. Furthermore, caloric restriction prevents the accumulation of senescent cells and helps retain autophagy activity in aging ASCs. These results suggest that caloric restriction and caloric restriction mimetics hold promise as a potential strategy to rejuvenate the stemness of aged ASCs. Further investigations, including in vivo evaluations using controlled interventions in animals and human studies, will be necessary to validate these findings and establish the clinical potential of this well-established approach for enhancing the stemness of aged stem cells.

Adipose Tissue Quantification Improves the Prognostic Value of GLIM Criteria in Advanced Gastric Cancer Patients.

The present study investigated whether the risk of recurrence after curative surgery could be further stratified by combining the Global Leadership Initiative on Malnutrition (GLIM) criteria and changes in subcutaneous (SAT) and visceral (VAT) adipose tissue mass after surgery in patients with advanced gastric cancer (AGC). This study retrospectively analyzed 302 patients with AGC who underwent curative surgery. Based on the GLIM criteria, patients were classified into malnourished and non-malnourished groups. The cross-sectional areas of SAT and VAT were measured from preoperative and 6-month post-operative computed tomography (CT) images. Multivariate survival analyses demonstrated that GLIM-defined malnutrition (p = 0.008) and loss of VAT after surgery (p = 0.008) were independent risk factors for recurrence-free survival (RFS). Evaluation of the prognostic value of combining the two independent predictors showed that malnourished patients with a marked loss of VAT had the worst 5-year RFS rate of 35.2% (p < 0.001). Preoperative GLIM-defined malnutrition and a loss of VAT during the first 6 months after surgery were independent predictors for RFS in patients with AGC. Changes in the VAT area after surgery could further enhance the prognostic value of the GLIM criteria for predicting the risk of gastric cancer recurrence.

Impact of preoperative subcutaneous adipose, visceral adipose and skeletal muscle on the outcomes of the oldest-old colorectal cancer patients after surgery

BackgroundColorectal cancer (CRC) is one of the most common tumors worldwide, with rising numbers of elderly patients affected. Nutritional status significantly influences tumor prognosis. We aimed to investigate the association of subcutaneous and visceral adipose tissue and skeletal muscle mass with the prognosis of the oldest-old patients with CRC, after surgery. PatientsWe retrospectively reviewed 210 patients >75 years who underwent surgical treatment at the Department of Gastrointestinal Surgery, Beijing Hospital, between December 2010 and December 2020. MaterialsSubcutaneous adipose, visceral adipose, and skeletal muscle areas were measured using BMI_CT. The cut-off values of the CT measurements were then confirmed using receiver operating characteristic (ROC) curve analysis. ResultsSubcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), and total adipose tissue index (TATI) were significantly associated with sex and BMI. Notably, the oldest-old CRC patients with high SATI, VATI, and TATI scores exhibited significantly higher rates of wound complications and reduced postoperative hospitalization durations. Intriguingly, patients with high VATI and TATI demonstrated significantly better 5-year Overall survival (OS), Cancer-specific survival (CSS), and Disease-free survival (DFS) than patients in the other groups. Similar results were observed in patients with a high visceral-to-subcutaneous fat ratio (VSR) and skeletal muscle index (SMI) scores. ConclusionSignificantly improving skeletal muscle content while concurrently managing the total adipose content, especially visceral adipose tissue, may aid in extending the survival time of oldest-old patients with CRC after surgery.

Abstract 12866: Increased Left Ventricular Mass Has Greater Association With Fat Free Mass Than Fat Mass in Black and White Females

Introduction: Increased left ventricular mass (LVM) is a risk factor for adult CV disease and is associated with increased body mass including obesity. The effects of different measures of body composition on LVM in young adulthood are not well described. Goals/Aims: Utilizing an existing longitudinal data set of black and white female young adults, we aimed to determine the contribution of various types of body composition measures to increased LVM. Methods: Data from the National Growth and Health Study, a study of racial differences in the development of obesity, including dual energy X-ray absorptiometry (DEXA), MRI, and echocardiogram (collected at ages 24-27) were analyzed. Logistic regression was conducted and receiver-operator characteristic (ROC) curves compared to assess the contribution of fat mass by DEXA (FM), fat-free mass by DEXA (FFM), subcutaneous adipose tissue mass by MRI (SAT), and visceral adipose tissue mass by MRI (VAT) towards the development of LVH (defined as LVMI ≥ 38.6 g/m 2.7 ). Multiple linear regression analyses were performed to assess for contributions to LVMI. Results: 550 women were included in the analysis (52.6% Black, mean age 24.9 ± 0.7 years at baseline). Using logistic regression, FM, FFM, SAT, and VAT were significantly associated with LVH (p &lt; 0.0001 for all), adjusting for SBP, DBP, and race. The ROC for FFM is greater than FM, SAT, and VAT (0.849 vs. 0.832, 0.813, and 0.788 respectively). In linear regression, FFM and DBP were significant contributors to LVMI. Black race was a significant predictor of LVH in the visceral fat model. There were no other significant racial differences. Conclusions: FFM had the greatest association with LVM, confirming previously published data. While the contribution of FFM towards the development of LVH was greater than that of FM and BP, FM and BP are modifiable risk factors and thus targets for clinical intervention.

Limosilactobacillus reuteri BIO7251 administration improves metabolic phenotype in obese mice fed a high fat diet: an inter-organ crosstalk between gut, adipose tissue and nervous system

Gut microbiota is implicated in the control of host physiology by releasing bioactive actors that could exert a direct or indirect effect on tissue. A dysfunction of the gut microbiota to tissue axis could participate in the development of pathological states such as obesity and diabetes. The aim of this study was to identify the metabolic effect of Limosilactobacillus reuteri (known as Lactobacillus reuteri) BIO7251 (L. reuteri BIO7251) isolated from Corsican clementine orange. Body weight gain, adiposity, glucose tolerance, glucose absorption and food intake were measured in mice fed a high-fat diet in response to a preventive oral administration of L. reuteri BIO7251. This strain of bacteria exerts a beneficial effect on body weight gain by decreasing the subcutaneous adipose tissue mass. The treatment with L. reuteri BIO7251 decreases glucose absorption and food intake in obese/diabetic mice. L. reuteri BIO7251 could be tested as new probiotic strain that could manage body weight during obesity.

Alisol B blocks the development of HFD-induced obesity by triggering the LKB1-AMPK signaling in subcutaneous adipose tissue

As a global epidemic disease, obesity causes dysfunction of glucose and lipid metabolism leading to persistently high morbidity and mortality. Given the difficulty to achieve and maintain weight loss through controlling diet and physical exercise, pharmacotherapy is considered an effective treatment for obesity. This investigation revealed that alisol B, a triterpene monomer isolated from the classical Chinese medicine Alisma orientale (Sam.) Juzep, functioned in suppressing adipogenesis and reducing the mass of subcutaneous adipose tissue, resulting in the reduction of weight gain, and improvements of hyperglycemia, hyperlipidemia, and insulin resistance in HFD-induced obese mice. In consistent to the results, alisol B also significantly inhibited adipocyte differentiation and maturation in vitro. Furthermore, our data revealed that the effects of alisol B on adipogenesis were mediated by LKB1-AMPK signaling pathway. In total, alisol B could be a potential lead compound which contributes to the improvement of obesity-related metabolic disorders.

Association of a lifestyle score with cardiometabolic markers among individuals with diabetes: a cross-sectional study

IntroductionTo investigate the associations of a lifestyle score with various cardiovascular risk markers, indicators for fatty liver disease as well as MRI-determined total, subcutaneous and visceral adipose tissue mass in...

Anti-obesity effects of aerobic exercise along with Rosa canina seed extract supplementation in rats: The role of irisin and adipolin

Aerobic exercise and some bioactive compounds in medicinal plants have anti-obesity effects and can suppress body weight. The aim of this study was to determine the anti-obesity effects of 6 weeks of aerobic exercise (AE) and supplementation of the hydroalcoholic extract of Rosa canina fruit seed (RC) in obese male rats. In this experimental study, 24 high-fat diet (HFD) obese male Wistar rats were used. The animals were randomly divided into 4 groups (6 rat in group), including 1. HFD (the control group), 2. HFD + AE, 3. HFD + RC and 4. HFD + AE + RC. An obesity protocol was implemented for 12 weeks with the consumption of HFD along with the consumption of water containing 1 % fructose. Afterwards, the animals were given access only to HFD food until the end of the study in all the groups. After the obesity protocol, 6 weeks of exercise (50–70 % VO2 max) and access to the extract (1 % of the consumed food) were given. Bodyweight, subcutaneous adipose tissue mass, and some serum lipid profiles were measured in the experimental groups. The serum levels of irisin and adipolin were evaluated by the ELISA method. Expression of FNDC5 and CTRP12 in adipose tissue were determined by real-time PCR. The findings of this study showed that body weight (P = 0.001), subcutaneous adipose tissue mass (P = 0.001), and lipid profile were significantly reduced in HFD + AE and HFD + AE + RC groups compared with the HFD group. Irisin was significantly increased in the HFD + AE and HFD + AE + RC groups compared with the HFD group (P = 0.019 and P = 0.001; respectively) and in the HFD + AE + RC group compared with the HFD + RC group (P = 0.004). Moreover, adipolin, expression of FNDC5 and CTRP12 were significantly increased in the HFD + AE + RC group compared with the HFD group (P = 0.004, P = 0.023, and P = 0.001; respectively). Altogether, HFD + AE with HFD + RC diet supplementation could reduce weight and the risks of obesity, at least, through the up-regulation of irisin and adipolin.

Long-term Outcome of Body Composition, Ectopic Lipid, and Insulin Resistance Changes With Surgical Treatment of Acromegaly.

Acromegaly presents a unique pattern of lower adiposity and insulin resistance in active disease but reduction in insulin resistance despite a rise in adiposity after surgery. Depot-specific adipose tissue masses and ectopic lipid are important predictors of insulin resistance in other populations, but whether they are in acromegaly is unknown. Long-term persistence of body composition changes after surgery is unknown. To determine how depot-specific body composition and ectopic lipid relate to insulin resistance in active acromegaly and whether their changes with surgery are sustained long-term. Cross-sectional study in patients with active acromegaly and longitudinal study in newly diagnosed patients studied before and in long-term follow-up, 3 (1-8) years (median, range), after surgery. Seventy-one patients with active acromegaly studied cross-sectionally and 28 with newly diagnosed acromegaly studied longitudinally. Main outcome measures were visceral (VAT), subcutaneous (SAT), and intermuscular adipose tissue masses by whole-body magnetic resonance imaging; intrahepatic lipid (IHL) by proton magnetic resonance spectroscopy; insulin resistance measures derived from fasting; and oral glucose tolerance test insulin and glucose levels. SAT and insulin-like growth factor 1 level, but not VAT or IHL, were independent predictors of insulin resistance in active acromegaly. VAT, SAT, and IHL gains were sustained long-term after surgery. VAT mass rise with surgery correlated inversely with rise in QUICKI while SAT rise correlated with fall in the Homeostatic Model Assessment score. SAT and disease activity are important predictors of insulin resistance in active acromegaly. Adiposity gains are sustained long-term after surgical treatment and impact on the accompanying improvement in insulin resistance.

The relationship between obesity and bone mineral density in children and adolescents: analysis of the National Health and Nutrition Examination Survey.

This study observed the relationship between fat mass and distribution, and areal bone mineral density (aBMD) in children and adolescents. A retrospective study was conducted on US children and adolescents aged 8-19years. Whole body (less head) aBMD was evaluated. Height (Ht) adjusted Z-scores for aBMD were calculated. After controlling for age, gender, race, and lean body mass index (LBMI) Z-score, there were significant negative associations between fat mass index (FMI) Z-score and aBMD Ht-Z-adjusted Z-score (β = - 0.272, P < 0.001, R2 = 0.033). In the linear regression models with aBMD Ht-Z-adjusted Z-score as the dependent variable, the regression coefficients of android fat mass were - 0.241 (P < 0.05, R2 = 0.002), - 0.473 (P < 0.001, R2 = 0.036), and - 0.474 (P < 0.001, R2 = 0.038) for healthy weight, overweight, and obesity group, respectively. The regression coefficients of visceral adipose tissue (VAT) mass were - 0.218 (P > 0.05, R2 = 0.001), - 2.025 (P < 0.001, R2 = 0.044), and - 1.826 (P < 0.001, R2 = 0.039), and the regression coefficients of subcutaneous adipose tissue (SAT) mass were - 0.467 (P < 0.001, R2 = 0.004), - 0.339 (P < 0.01, R2 = 0.024), and - 0.347 (P < 0.001, R2 = 0.018) for healthy weight, overweight, and obesity group, respectively. The present study suggests that fat mass has a slightly negative association with bone development in children and adolescents. Trunk fat accumulation, especially visceral adipose tissue, was correlated with the lower level of aBMD. This association was obvious in overweight and obese children.

Risk Stratification Based on a Pattern of Immunometabolic Host Factors Is Superior to Body Mass Index-Based Prediction of COVID-19-Associated Respiratory Failure.

Overweight and obesity are associated with chronic low-grade inflammation and represent risk factors for various diseases, including COVID-19. However, most published studies on COVID-19 defined obesity by the body mass index (BMI), which does not encounter adipose tissue distribution, thus neglecting immunometabolic high-risk patterns. Therefore, we comprehensively analyzed baseline anthropometry (BMI, waist-to-height-ratio (WtHR), visceral (VAT), epicardial (EAT), subcutaneous (SAT) adipose tissue masses and liver fat, inflammation markers (CRP, ferritin, interleukin-6), and immunonutritional scores (CRP-to-albumin ratio (CAR), modified Glasgow prognostic score, neutrophile-to-lymphocyte ratio, prognostic nutritional index)) in 58 consecutive COVID-19 patients of the early pandemic phase with regard to the necessity of invasive mechanical ventilation (IMV). Here, metabolically high-risk adipose tissues represented by increased VAT, liver fat, and WtHR strongly correlated with higher levels of inflammation, pathologic immunonutritional scores, and the need for IMV. In contrast, the prognostic value of BMI was inferior and absent with regard to SAT. Multivariable logistic regression analysis identified an optimized IMV risk prediction model employing liver fat, WtHR, and CAR. In summary, we suggest an immunometabolically risk-adjusted model to predict COVID-19-induced respiratory failure better than BMI-based stratification, which warrants prospective validation.

Interscapular fat is associated with impaired glucose tolerance and insulin resistance independent of visceral fat mass.

Dysregulated body fat distribution is a major determinant of various diseases. In particular, increased visceral fat mass and ectopic lipids in the liver are linked to metabolic disorders such as insulin resistance and type 2 diabetes. Furthermore, interscapular fat is considered to be a metabolically active fat compartment. This study measured interscapular fat mass and investigated its relationship with glucose metabolism in 822 individuals with a wide range of BMI values and different glucose tolerance statuses. Magnetic resonance imaging was used to quantify body fat depots, and an oral glucose tolerance test was performed to determine glucose metabolism. Elevated interscapular fat mass was positively associated with age, BMI, and total body, visceral, and subcutaneous adipose tissue mass. High interscapular fat mass associated with elevated fasting glucose levels, glucose levels at 2 hours during the oral glucose tolerance test, glycated hemoglobin, and insulin resistance, independent of sex, age, and total body and visceral fat mass. In conclusion, interscapular fat might be a highly specific fat compartment with a potential impact on glucose metabolism and the pathogenesis of diabetes mellitus.

Discovery of a novel anti-obesity meroterpenoid agent targeted subcutaneous adipose tissue

BackgroundMeroterpenoid furanasperterpene A (T2–3) with a novel 6/6/6/6/5 pentacyclic skeleton was isolated from the Aspergillus terreus GZU-31–1. Previously, we showed that T2–3 possessed significant lipid-lowering effects in 3T3-L1 adipocytes at 5 μM concentration. However, its therapeutic effect in metabolic disease and the underlying mechanisms of action remain unclear. MethodsHigh fat diet-induced obesity (DIO) mouse model and 3T3-L1 cell model were used to assess the anti-obesity effects of T2–3. Lipids in the adipocytes were examined by Oil Red O staining. β-catenin expression was examined by immunofluorescence and Western blotting, its activity was assessed by TOPflash/FOPflash assay. ResultsT2–3 possessed potent anti-obesity effects in DIO mice, it significantly reduced body weight and subcutaneous adipose tissue (SAT) mass. Mechanistic studies showed that T2–3 significantly inhibited 3T3-L1 preadipocyte differentiation as indicated by the reduced number of mature adipocytes. The treatments also reduced the expressions of critical adipogenic transcription factors CEBP-α and PPAR-γ in both 3T3-L1 adipocytes and SAT in DIO mice. Interestingly, T2–3 increased the cytoplasmic and nuclear expressions of β-catenin and the transcriptional activity of β-catenin in 3T3-L1 adipocytes; the elevated β-catenin expression was also observed in SAT of the T2–3-treated DIO mice. Indeed, upregulation of β-catenin activity suppressed adipogenesis, while β-catenin inhibitor JW67 reversed the anti-adipogenic effect of T2–3. Taken together, our data suggest that T2–3 inhibits adipogenesis by upregulating β-catenin activity. ConclusionsOur study is the first report demonstrating meroterpenoid furanasperterpene A as a novel 6/6/6/6/5 pentacyclic skeleton (T2–3) that possesses potent anti-adipogenic effect by targeting β-catenin signaling pathway. Our findings drive new anti-obesity drug discovery and provide drug leads for chemists and pharmacologists.

Non-invasive cooling wear as an effective means of reducing subcutaneous adipose tissue mass: an in-vivo study.

ObjectiveThe increasing prevalence of obesity is a major health problem worldwide. Several non-surgical treatments are now available that reduce body and subcutaneous fat mass. We aimed to determine the efficacy of mild cold for body mass reduction.MethodsNovel cooling wear, which induces mild cooling via evaporation, was worn by 29 women with overweight for 4 weeks. Specifically, the participants wore a cooling waist belt and chaps for 1 hour per day. Non-invasive lipometry was used to determine their subcutaneous adipose tissue thicknesses, and the total weight loss, abdominal circumference, and body mass index (BMI) of the participants were measured.ResultsThe participants achieved a significant total weight loss of 0.7 kg (0.9%), and significant reductions in BMI (0.2 kg/m2) and abdominal circumference (1.9 cm, 1.7%). Furthermore, there was a trend towards a reduction in abdominal subcutaneous fat thickness and a significant reduction in thickness of the anterior thigh was noted. A questionnaire-based evaluation indicated high usability and comfort of the cooling wear.ConclusionThere is a high and growing demand for non-invasive treatment strategies for obesity. Cooling wear represents a novel and promising approach that may be of particular use for individuals who do not require bariatric surgery.

Loss of Adipocyte STAT5 Confers Increased Depot-Specific Adiposity in Male and Female Mice That Is Not Associated With Altered Adipose Tissue Lipolysis

STATs (Signal Transducers and Activators of Transcription) 5A and 5B are induced during adipocyte differentiation and are primarily activated by growth hormone (GH) and prolactin in fat cells. Previous studies in mice lacking adipocyte GH receptor or STAT5 support their roles in lipolysis-mediated reduction of adipose tissue mass. Male and female mice harboring adipocyte-specific deletion of both STAT5 genes (STAT5AKO) exhibit increased subcutaneous or inguinal adipose tissue mass, but no changes in visceral or gonadal fat mass. Both depots display substantial increases in adipocyte size with no changes in lipolysis in adipose tissue explants. RNA sequencing analysis of subcutaneous adipose tissue and indirect calorimetry experiments reveal sex-dependent differences in adipose gene expression and whole-body energy expenditure, respectively, resulting from the loss of adipocyte STAT5.