Changes In Subcutaneous Adipose Tissue Research Articles

Discordant gene expression in subcutaneous adipose and skeletal muscle tissues in response to exercise training.

Exercise has different effects on different tissues in the body, the sum of which may determine the response to exercise and the health benefits. In the present study, we aimed to investigate whether physical training regulates transcriptional network communites common to both skeletal muscle (SM) and subcutaneous adipose tissue (SAT). Eight such shared transcriptional communities were found in both tissues. Eighteen young overweight adults voluntarily participated in 7 weeks of combined strength and endurance training (five training sessions per week). Biopsies were taken from SM and SAT before and after training. Five of the network communities were regulated by training in SM but showed no change in SAT. One community involved in insulin- AMPK signaling and glucose utilization was upregulated in SM but downregulated in SAT. This diverging exercise regulation was confirmed in two independent studies and was also associated with BMI and diabetes in an independent cohort. Thus, the current finding is consistent with the differential responses of different tissues and suggests that body composition may influence the observed individual whole-body metabolic response to exercise training and help explain the observed attenuated whole-body insulin sensitivity after exercise training, even if it has significant effects on the exercising muscle.

Differences in the Impact of Various Types of Exercise on Irisin Levels: A Systematic Review and Meta-Analysis.

Irisin, a myokine that is responsive to exercise, induces significant changes in subcutaneous adipose tissue. By promoting the browning of white fat tissue, it enhances energy expenditure, thereby addressing overweight and obesity. This systematic review and meta-analysis aimed to compare the effects of different types of physical exercises on irisin levels in overweight and obese adults. Specifically, the review focused on studies involving obese or overweight individuals who participated in exercise training for a minimum of 8 weeks, with measured and reported changes in serum irisin levels compared to a control group. Data were collected from four databases (Google Scholar, ISI Web of Science Core Collection, PubMed, and Scopus). The risk of bias was assessed using the Begg and Egger tests, and the results were synthesized. Initial searches identified 560 titles, out of which only seven met the criteria for inclusion in the systematic review. Statistical analysis demonstrated a significant increase in serum irisin concentration (SMD = 0.957, P = 0.005) among obese and overweight individuals who engaged in exercise, compared to the passive control group. High-intensity interval training (HIIT) (SMD = 1.229, P < 0.001) had a more pronounced effect on increasing serum irisin levels than other exercise protocols. Furthermore, the effectiveness of exercise varied based on the participants' weight status (significant changes for overweight individuals; P < 0.001 and insignificant changes for obese individuals; P = 0.1), age (significant changes for those under 40 years old; P < 0.001 and insignificant changes for those over 40 years old; P = 0.322), and gender (significant changes for men; P < 0.001 and insignificant changes for women; P = 0.285). Consequently, exercise can elevate serum irisin levels, leading to alterations in adipose tissue phenotype and thermogenesis, ultimately contributing to weight reduction in obese and overweight individuals.

Subcutaneous adipose tissue alteration in aging process associated with thyroid hormone signaling

BackgroundFunctional changes in subcutaneous adipose tissue (SAT) occur earlier in the aging process and play an important role in the occurrence and development of age-related metabolic diseases. The mechanism of this phenomenon is still unclear, and the change in adipose tissue with age is poorly understood.MethodsWe used transcriptome sequencing (RNA seq) to screen differentially expressed genes at the mRNA level, and analyzed the functional characteristics of the differential genes through GO and KEGG analysis in human SAT of all ages. In order to clarify the specific mechanism of the functional change, we analyzed the chromatin accessibility in the promoter region in the same SAT used in the RNA seq by the assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and obtained the functional genes in SAT changed with age. To verify these changes, we enlarged our sample content of human SAT. The primary mice adipocytes were extracted and stimulated by thyroid hormone of different concentration to construct an animal model, and the expression of the genes were determined through real-time Polymerase Chain Reaction(RT-PCR). The oxygen consumption test and immunofluorescence staining were used to determine the mitochondrial function of SAT.ResultsRNA-seq showed characteristic gene expression of young and old human SAT, in which 331 genes were up-regulated and 349 genes were down-regulated. ATAC-seq, RNA-seq, combined with the mouse prediction model, determined the functional changed characteristics of seven genes. All these genes expressed differently in SAT of different ages, in which, NCF1, NLRP3, DUOX1 showed positive correlation with age; The expression of IFI30, P2RX1, P2RX6, PRODH, however, decreased with age. And all these genes showed dose dependent alternations under treatment of triiodothyroxine in mice SAT. The oxygen consumption rate revealed significant changes of the mitochondrial function and ROS accumulation in human SAT of different ages.ConclusionIn elderly individuals, the function, in addition to distribution, of SAT undergoes significant changes, primarily in mitochondria, which may be due to insensitivity to thyroid hormone signaling. These results identified seven novel genes regulated by thyroid hormone, exhibiting significant changes in SAT of different age, and are probably related to the dysfunction of the aged SAT due to the mitochondrial damage and ROS accumulation.

Tracing the Change and Contribution of Subcutaneous Adipose to Skin Expansion Using a Luciferase-Transgenic Fat Transplantation Model.

During skin expansion, subcutaneous adipose tissue undergoes the greatest change. The adipose layer appears to gradually thin or even disappear in long-term expansion. The response and contribution of adipose tissue to skin expansion remain to be elucidated. The authors established a novel expansion model by transplanting luciferase-transgenic adipose tissue into the rat dorsum, followed by integrated expansion, to trace the dynamic changes in subcutaneous adipose tissue during expansion and the migration of adipose tissue-derived cells. In vivo luminescent imaging was performed to continuously track the adipose tissue changes. Histologic analysis and immunohistochemical staining evaluated the regeneration and vascularization of the expanded skin. Growth factor expression in expanded skin with or without adipose tissue was determined to evaluate the paracrine effect of adipose tissue. Adipose tissue-derived cells were traced in vitro by anti-luciferase staining, and their fate was determined by costaining for PDGFRα, DLK1, and CD31. In vivo bioimaging showed that cells in adipose tissue were alive during expansion. After expansion, the adipose tissue exhibited fibrotic-like structures, with more DLK1 + preadipocytes. Skin expanded with adipose tissue was significantly thicker than that without adipose tissue, with more blood vessels and cell proliferation. Vascular endothelial growth factor, epidermal growth factor, and basic fibroblast growth factor expression was higher in adipose tissue than in skin, indicating paracrine support from adipose tissue. Luciferase-positive adipose tissue-derived cells were observed in expanded skin, indicating direct participation in skin regeneration. Adipose tissue transplantation can effectively promote long-term skin expansion by contributing to vascularization and cell proliferation by means of various mechanisms. The authors' findings suggest that it would be better if the expander pocket is dissected over the superficial fascia to preserve a layer of adipose tissue with skin. In addition, their findings support the treatment of fat grafting when expanded skin presents with thinning.

The lipidomic and inflammatory profiles of visceral and subcutaneous adipose tissues are distinctly regulated by the SGLT2 inhibitor empagliflozin in Zucker diabetic fatty rats

The pharmacological inhibition of sodium-glucose cotransporter 2 (SGLT2) has emerged as a treatment for patients with type 2 diabetes mellitus (T2DM), cardiovascular disease and/or other metabolic disturbances, although some of the mechanisms implicated in their beneficial effects are unknown. The SGLT2 inhibitor (SGLT2i) empagliflozin has been suggested as a regulator of adiposity, energy metabolism, and systemic inflammation in adipose tissue. The aim of our study was to evaluate the impact of a 6-week-empagliflozin treatment on the lipidome of visceral (VAT) and subcutaneous adipose tissue (SAT) from diabetic obese Zucker Diabetic Fatty (ZDF) rats using an untargeted metabolomics approach. We found that empagliflozin increases the content of diglycerides and oxidized fatty acids (FA) in VAT, while in SAT, it decreases the levels of several lysophospholipids and increases 2 phosphatidylcholines. Empagliflozin also reduces the expression of the cytokines interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNFα), monocyte-chemotactic protein-1 (MCP-1) and IL-10, and of Cd86 and Cd163 M1 and M2 macrophage markers in VAT, with no changes in SAT, except for a decrease in IL-1β. Empagliflozin treatment also shows an effect on lipolysis increasing the expression of hormone-sensitive lipase (HSL) in SAT and VAT and of adipose triglyceride lipase (ATGL) in VAT, together with a decrease in the adipose content of the FA transporter cluster of differentiation 36 (CD36). In conclusion, our data highlighted differences in the VAT and SAT lipidomes, inflammatory profiles and lipolytic function, which suggest a distinct metabolism of these two white adipose tissue depots after the empagliflozin treatment.

IDF2022-0109 MicroRNA expression in subcutaneous adipose tissue changes in response to exercise training in obese African women

IDF2022-0109 MicroRNA expression in subcutaneous adipose tissue changes in response to exercise training in obese African women

Empagliflozin treatment differentially modifies visceral and subcutaneous adipose tissue lipidomes and pro-inflammatory cytokines in zucker fatty diabetic rats

Abstract EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial) trial highlighted the relevance of pharmacological inhibition of sodium-glucose cotransporter 2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus (T2DM) and/or cardiovascular disease. Although the pathways through which SGLT2 inhibitors exert a beneficial effect on the cardiovascular system are still unknown, it has been suggested that energy metabolism regulation and a reduction of systemic inflammation could be some of the mechanisms implicated. Available data also suggests that empagliflozin treatment could be able to exert regulatory effects on adipose tissue (AT) depots. The aim of our study was to evaluate the impact of empagliflozin treatment on the lipidome of visceral (VAT) and subcutaneous adipose tissue (SAT) depots in a rat model of obesity and T2DM. Diabetic obese Zucker Fatty (ZDF) rats were treated with 30 mg/kg/day of empagliflozin p.o for 6 weeks. The lipidomes of VAT and SAT depots were analyzed using ultra-high performance liquid chromatography coupled to mass spectrometry. Empagliflozin's effect on pro-inflammatory markers in AT was analyzed by RT-PCR. In VAT, 18 metabolites were significantly altered in empagliflozin-treated rats vs. controls. Nearly all diglycerides tested (13 of 14) were significantly increased in treated rats, as the most notable altered chemical class. Furthermore, 3 oxidized fatty acids (FA) and FA like gadoleic acid and linoleic acid were also significantly increased. In SAT, a total of 14 metabolites were significantly altered. Most of them (13 of 14) were glycerophospholipids. Significantly lower levels of 4 lysophosphatidylethanolamines, 4 lysophosphatidylcholines, and 3 lysophosphatidylinositols and higher levels of 2 phosphatidylcholines were shown. In contrast to VAT, a significant decrease in most of these metabolites was observed in empagliflozin-treated samples. Several ratios of metabolites were also calculated to infer the potential enzyme activities related to lipid metabolism in both VAT and SAT. However, the ratios studied were only statistically significant in VAT of empagliflozin-treated rats vs. control, where the main potential enzyme activities altered were desaturases and elongases. Empagliflozin treatment also reduces the expression of the pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα) and monocyte-chemotactic protein-1 (MCP-1) in VAT, with no changes in SAT, except for interleukin-13 (IL-13), which also decreases compared to untreated diabetic ZDF rats. In conclusion, empagliflozin increased oxidized FA and diglycerides in VAT and decreased glycerophospholipid levels in SAT. The anti-inflammatory effect of empagliflozin in VAT is not observed in SAT. The effect of empagliflozin on the regulation of the adipose tissue lipidome and inflammatory profile is different depending on the localization of the depots. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim Pharma GmbH and Co

Effects of age on subcutaneous adipose tissue proteins in Chinese indigenous Ningxiang pig by TMT-labeled quantitative proteomics

Adipose tissue not only affects meat quality and animal productivity, but also participates in inflammation and immunity. Ningxiang pig is famous for their excellent meat quality, disease resistance and tolerance of roughage. It is not yet well known how proteins in adipose tissue is dynamically regulated during the growth of Ningxiang pig. This report studies the proteomic changes in subcutaneous adipose tissue in Ningxiang pigs to gain a better understanding of the molecular mechanism of fat development during the growth period. By TMT-labeled quantitative proteomic analysis of subcutaneous adipose tissue of 9 purebred Ningxiang pigs of different ages, we identified 2533 unique proteins and 716 differentially abundant proteins (DAPs), of which more than half of the DAPs were concentrated in the 90d-210d period. Retrograde endocannabinoid signaling was only significantly enriched in DAPs of N90d vs N30d, Alcoholism and Graft-versus-host disease were only significantly enriched in DAPs of N210d vs N90d. Proteins related to dilated cardiomyopathy was found to be an important pathway in fat development and lipid metabolism. A variety of novel DAPs involved in maintaining mitochondrial function and cell viability, such as NDUFS6, SDHB, COX5A, ATP5D and TNNT1, which play a role in controlling the prediction networks, may indirectly regulate the development and functional maintenance of adipocytes. SignificanceThese age-dependent DAPs discovered in this study may help expand the understanding of the molecular mechanisms of the development, function maintenance and transformation of adipose tissue in Ningxiang pig for developing new strategies for improving meat quality and pig breeding in the future.

240-LB: Adipogenesis in Weight Regain Does Not Accelerate Adiposity in Mice

Weight loss and regain are associated with profound cytoskeleton changes in collapsing and re-expanding adipocytes. These drastic changes in the adipose tissue may drive proinflammatory signalling and fibrotic processes during weight regain. It remains unclear how adipose tissue re-expansion affects adipose tissue function and thereby the comorbidities related to obesity. The aim of this study was to characterize structural and metabolic changes in subcutaneous adipose tissue after weight loss and regain in diet-induced obesity (DIO) mice. DIO mice underwent calorie restriction to achieve a 25% weight loss and then returned to ad libitum high fat diet feeding to regain weight. Inguinal adipose tissue was collected and analysed from five groups of mice during the experiment: before high fat diet feeding (Lean) , before weight loss (DIO 1) , after weight loss (WL) , after 3 weeks of weight regain (WR) and age-matched ad libitum DIO mice (DIO 2) . We found that WR group had lower weight and fat mass compared to DIO2 group (31.9±1.6 vs. 23.9±1.9 %) and lower basal lipolysis measured ex-vivo. We detected a larger population of small adipocytes in WR mice compared to DIO2 group, resulting in smaller average adipocyte size (81.6±1.4 vs. 52.5±0.9 µm) and increased expression of cell renewal markers Cidea, Antrx1 and Prkaa in adipose tissue, indicating activation of adipogenesis. Expression of cytokines Il2, Ccl19, Cdc3 in adipose tissue in WR compared to DIO was reduced as well as plasma levels of cytokines Il2, KC/GRO and Inf-γ. In conclusion, our study does not support that increased adipogenesis in weight regain results in accelerated fat accumulation in mice. Weight regain is accompanied by reduced systemic and adipose inflammation. This suggests in general a beneficial effect of regain-induced adipogenesis resulting in potentially healthier adipose tissue in mice. Weather these findings represent the human situation with weight loss and regain is unknown and is currently under investigation. Disclosure M. K. Gerstenberg: Employee; Novo Nordisk. R. E. Kuhre: Employee; Novo Nordisk. N. Petersen: Employee; Novo Nordisk A/S. A. Bookout: Employee; Novo Nordisk. C. M. Castorena: Employee; Novo Nordisk. L. Torz: Other Relationship; Novo Nordisk A/S. T. H. Dovmark: None. S. Lundh: Employee; Novo Nordisk A/S. S. H. Madsen: None. B. S. Andersen: Employee; Novo Nordisk A/S. T. A. Pedersen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S.

Can Point Shear Wave Elastography be Used as an Indicator of Metabolic Complications in Overweight Children and Adolescents? Evaluation of Subcutaneous Adipose Tissue

This study aims to search the association of obesity, metabolic parameters, and abdominal subcutaneous white adipose tissue (scWAT) stiffness in children and adolescents using ultrasound point shear wave elastography (p-SWE). One hundred and forty overweight or obese children referred to as overweight were included in the study group. Thirty-two lean children, referred to as leans, were included in the control group. In all individuals, scWAT shear wave speed (SWS) was measured with p-SWE. ScWAT stiffness was compared between the two groups. The association of anthropometric, metabolic factors and scWAT stiffness is determined. Weight, body mass index, body mass index-standard deviation score, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, fasting insulin were significantly higher in the overweight group (p&lt;0,05). ScWAT SWS was significantly different between the groups (p=0.006) The median value of scWAT SWS was 1,5 m/s (range; 0.9-3.8), 1.23 m/s (range; 0.7-3.1) for leans and overweight, respectively. In leans, no significant difference was found between boys and girls for scWAT SWS (p=0.094). In overweight, a significant difference was found for scWAT SWS between boys and girls (p=0.022). The scWAT stiffness is lower in overweight than leans. Gender has a pivotal role in scWAT stiffness. If supported with future long-time follow-up studies, p-SWE may be compatible with assessing subcutaneous adipose tissue changes related to obesity and metabolic complications in childhood and adolescence.

Gluteal subcutaneous adipose tissue in women of different ages and body mass index observed by magnetic resonance imaging.

Magnetic resonance imaging (MRI) is a recognized method to assess the morphological characteristics of subcutaneous adipose tissue (SAT). This study aimed to assess objectively different characteristics of SAT of women with different ages and body mass index (BMI) using MRI. Retrospective, observational study. Pelvic-MRI exams of 133 women aged between 15 and 80years, with BMI 16-30kg/m2 were assessed. There was a moderate positive correlation between the total fat thickness and the BMI (r=0.64; p<0.0001) considering the entire sample. Within the different age groups, strong positive correlation was observed for age groups 15 to 30years (r=0.76; p<0.0001) and 46 to 60years (r=0.75; p<0.0001), and moderate positive correlation in the others (r=0.61; p<0.0001 [31-45years] and r=0.53; p<0.0001 [>61years-old]). There was no correlation between age and fat layer thickness. Correlation between deep fat layer thickness and BMI showed similar pattern to that of the total fat layer. Within the different BMI groups, SAT thickness tends to decrease with aging in patients with low BMI. Inside each age group, the average thickness of the total fat layer increases according to BMI. The results suggest that BMI influences the thickness of SAT throughout life and how SAT changes with age in patients with different BMI. In patients with moderate BMI, the thickness of SAT remains stable.

Short communication: effect of dietary supplementation with a mixture of fish and sunflower oils on the expression of key lipogenic and cholesterologenic genes in adipose tissues with different metabolic functions.

The present study investigated the effects of dietary fish and sunflower oils as sources of n-3, n-6 polyunsaturated fatty acids (PUFA) on the expression of key lipogenic and cholesterologenic genes in subcutaneous adipose tissue (SAT) and tail adipose tissue (TAT) of fat-tailed sheep. Twenty-six male Afshari lambs were divided into 4 groups. Three groups were fed a high concentrate basal diet plus 100g/lamb/day oil supplement (OS; 60g sunflower oil and 40g fish oil) beyond a 21-day adaptation period for 10, 20, and 30days (groups OS10, OS20, and OS30; n = 6, each) until slaughter. A control group was slaughtered at the last day of adaptation (OS0; n = 4). Expression of PPARγ, SREBP-1c, and SREBP-2 were determined in TAT and SAT. All transcription factors had lower expression in SAT than TAT. Feeding OS induced a similar pattern of SREBP-1c expression in both TAT and SAT with highest values in OS20. SREBP-2 mRNA decreased by > 50% in TAT of OS30 compared to OS0, whereas the expression ofSREBP-2 mRNA did not changein SAT in the same period. PPARγ expression was not affected over time either in SAT or TAT.Plasma concentrations of cholesterol and blood urea nitrogen increased in OS20. The comparison of gene expression responses to OS in TAT vs. SAT suggest that PUFA-mediated effects on lipid metabolism differ between SAT and TAT, which may be linked to the specific role of TAT in energy and water balance under arid conditions.

Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass

Menopause is associated with a redistribution of adipose tissue towards central adiposity, known to cause insulin resistance. In this cross-sectional study of 33 women between 45 and 60 years, we assessed adipose tissue inflammation and morphology in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) across menopause and related this to menopausal differences in adipose tissue distribution and insulin resistance. We collected paired SAT and VAT biopsies from all women and combined this with anthropometric measurements and estimated whole-body insulin sensitivity. We found that menopause was associated with changes in adipose tissue phenotype related to metabolic dysfunction. In SAT, postmenopausal women showed adipocyte hypertrophy, increased inflammation, hypoxia and fibrosis. The postmenopausal changes in SAT was associated with increased visceral fat accumulation. In VAT, menopause was associated with adipocyte hypertrophy, immune cell infiltration and fibrosis. The postmenopausal changes in VAT phenotype was associated with decreased insulin sensitivity. Based on these findings we suggest, that menopause is associated with changes in adipose tissue phenotype related to metabolic dysfunction in both SAT and VAT. Whereas increased SAT inflammation in the context of menopause is associated with VAT accumulation, VAT morphology is related to insulin resistance.

Longitudinal Changes in Body Composition Following Hematopoietic Cell Transplantation

Sarcopenia, the loss of skeletal muscle tissue, has been identified as a potential risk factor for adverse outcomes in hematopoietic cell transplantation (HCT) recipients. However, much remains unknown about longitudinal changes in body composition following HCT. We retrospectively evaluated computed tomography (CT) imaging from 315 lymphoma patients undergoing HCT at our institution between 2000 and 2014. Two HCT cohorts were established: auto-HCT (did not receive allo-HCT, n=218) and allo-HCT (may have received previous auto-HCT, n=97). Cross-sectional area of lean muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were measured at the level of the third lumbar vertebral body (L3) on an axial CT image prior to HCT, 1 year post-HCT, and 2.5 years post-HCT. Lean muscle was normalized for height and reported as L3 skeletal muscle index (L3SMI). Sarcopenia was defined as L3SMI ≤39 cm2/m2 for women and ≤55 cm2/m2for men.Sarcopenia prior to HCT was observed in 50% of HCT recipients, 47% in the auto-HCT cohort and 57% in the allo-HCT cohort. The number of lines of therapy prior to HCT was predictive of sarcopenia prior to HCT (OR=1.29, p=.01). There was a significant decline in skeletal muscle mass over time for patients in the allo-HCT cohort when compared to the trend in the auto-HCT cohort (-6.52 cm2/imaging interval, p=<0.01) (Figure 1). In the allo-HCT cohort, the association between the change in muscle mass (per cm2) from prior to HCT to 2.5 years post-HCT and moderate-severe chronic GVHD did meet statistical significance (OR 1.04, p=0.03). The incidence of sarcopenia increased over time in all patients receiving HCT (OR=1.55; p=0.02), particularly driven by patients undergoing allo-HCT who experienced an increased rate of sarcopenia over time compared to auto-HCT (OR=1.66, p=0.02). The incidence of sarcopenia reached 66% at 2.5 years post-HCT in the allo-HCT cohort (Figure 2). In the allo-HCT cohort, the association between sarcopenia at 2.5 years post-HCT and moderate-severe chronic GVHD did not meet statistical significance (OR 3.32, p=0.07). Adipose tissue analysis showed allo-HCT recipients had lower measurements of SAT at all time point when compared to patients in the auto-HCT cohort. There was a significant increase in both VAT and SAT experienced by recipients of auto-HCT and allo-HCT when comparing CT images from 1 year post-HCT and 2.5 years post-HCT (p<0.05). However, there was no significant difference in change in SAT or VAT over time when comparing auto-HCT and allo-HCT cohorts.In conclusion, retrospective analysis of CT imaging revealed significant loss of muscle mass and an increased incidence of sarcopenia following HCT, especially in patients undergoing allo-HCT. Future studies are needed to further characterize changes in body composition in HCT recipients and investigate its impact on HCT outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

254-OR: Bariatric Surgery Influences Insulin Sensitivity through Changes in Subcutaneous Adipose Tissue (SAT) Characteristics

Although literature describes the influence of bariatric surgery on insulin sensitivity (IS) showing improvement in metabolic parameters, including sustained remission of type 2 diabetes and reduction in cardiovascular disease, the underlying mechanisms remain unclear. Changes in SAT following bariatric surgery make it a key site for investigating mechanisms of glucose control. To test whether changes in SAT are related to improved IS following bariatric surgery, we quantified adipose cell size distribution in SAT harvests, in addition to quantifying insulin resistance (IR) using the steady-state plasma glucose (SSPG) test in 57 obese subjects undergoing bariatric surgery at baseline and one year post surgery. We compared IR and SAT size variables in the post-surgical subjects to those of BMI-matched non-surgical controls. Surgery subjects (n=57) were healthy, morbidly obese men and women without diabetes, ages 23-70, with BMI &amp;gt; 35 kg/m^2, who underwent bariatric surgery, while controls (n=43) were healthy, men and women without diabetes ages 23-70 years with BMIs 22-38.3kg/m^2. Of the surgery subjects, 14 were available at 1 year post-surgery for comparison with controls. Compared to pre-surgery, post-surgery results demonstrated a decrease in average BMI, weight, SSPG, peak diameter, nadir, and percent small cells (p&amp;lt;.05). Compared to the controls (BMI 30.9 +- 4.0 kg/m^2), the post-surgical subjects (BMI 30.5 +/- 3.8 kg/m^2) demonstrated reduced IR, percent small cells, and adipose cell peak diameters, p&amp;lt;0.001. After surgery, SAT exhibits features of healthier fat cells compared to controls, which may account for their lower IR. Independent of weight loss, adipocyte cell qualities may play a role in the improvement in IS due to bariatric surgery. These observations have implications in treatments targeting type 2 diabetes and cardiovascular disease because manipulating fat cell size and percent of small cells may provide a path to improving IS. Disclosure A. Lenz: None. T. Mclaughlin: Board Member; Self; January, Inc. E. J. Zanley: None. Funding American Heart Association; National Institutes of Health

Castration induced circRNA expressional changes in subcutaneous adipose tissue of male pigs.

Circular RNAs (circRNAs) participated in regulation of lipid metabolism; however, its functional role on castration-induced lipid deposition has not been deeply researched. So in this research, we firstly compared circRNAs expressional differences in subcutaneous adipose tissue between intact and castrated male Huainan pigs. A total of 6116 differentially expressed circRNAs (DECs) were detected between these two groups (|log2 foldchange| ≥ 1 and padj ≤ 0.05); GO and KEGG analysis showed that their parent genes were mainly enriched in metabolism-related pathway. And TGF-beta, insulin, AMPK, and MAPK pathways might play vital role in castration-induced lipid deposition. The miRNAs enriched in the constructed circRNA-miRNA network were mainly participated in adipogenesis and lipid metabolism, such as miR-143a-3p, miR-378, and miR-195. And it was verified that testosterone upregulated miR-181a but downregulated circ_0005912 expression in a dose-dependent manner in porcine intramuscular adipocytes, and overexpression of miR-181a inhibited circ_0005912. Taken together, these DECs may participate in the regulation of lipid metabolism after castration by reaction with miRNAs, which indicated the novel role of circRNAs in castration-induced lipid deposition.

Effects of CPAP therapy on subcutaneous adipose tissue in patients with obstructive sleep apnea: a meta-analysis.

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA). However, studies provide conflicting results on the effects of CPAP on subcutaneous adipose tissue (SAT) in patients with OSA. We therefore performed a meta-analysis to evaluate whether or not CPAP has an effect on SAT in patients with OSA. Studies were retrieved by searching the Cochrane Library, Web of Science, Embase, and Pubmed. Information on study and patient characteristics, study design, and SAT pre- and post-CPAP treatment was extracted for analysis. Different methods for measurement of SAT were also notated. Standardized mean difference (SMD) and 95% confidence interval (CI) were measured to estimate the change in SAT before and after CPAP treatment. Meta-analysis was performed using the RevMan v.5.3 and Stata 14.0. A total of 10 studies met inclusion criteria encompassing 309 patients in the final analysis. The pooled estimate showed that CPAP treatment resulted in no significant change in SAT (SMD = - 0.014, 95% CI = - 0.161 to 0.133, p = 0.896). Meta-regression analyses revealed no predictor, including methods of measuring SAT, that influenced the CPAP effect on SAT. Our meta-analysis demonstrated that after CPAP therapy, there was no significant change in SAT in patients with OSA.

Lipid Profiling Reveals Browning Heterogeneity of White Adipose Tissue by Β3-Adrenergic Stimulation.

Background: White adipose tissue (WAT) browning confers beneficial effects on metabolic diseases. However, visceral adipose tissue (VAT) is not as susceptible to browning as subcutaneous adipose tissue (SAT). Aim: Interpreting the heterogeneity of VAT and SAT in brown remodeling and provide promising lipid targets to promote WAT browning. Methods: We first investigated the effects of β3-adrenergic stimulation by CL316,243 on systemic metabolism. Then, high-coverage targeted lipidomics approach with multiple reaction monitoring (MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT. Results: CL316,243 notably ameliorated the systemic metabolism and induced brown remodeling of SAT but browning resistance of VAT. Comprehensive lipidomics analysis revealed browning heterogeneity of VAT and SAT with more dramatic alteration of lipid classes and species in VAT rather than SAT, though VAT is resistant to browning. Adrenergic stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. Conclusions: We demonstrated the browning heterogeneity of WAT and identified potential lipid biomarkers which may provide lipid targets for overcoming VAT browning resistance.

Review article: The Effect of Exercise On Fat Browning through Plasma Irisin Level Modulation to Overcome Obesity

Overweight and obesity incidence continues to increase and becomes a global problem in recent decades. One of the pathophysiology is a low energy output, therefore energy homeostasis shifts positively. Exercise is considered as an effective method to increase energy output. Irisin is one of myokine type that is secreted to the bloodstream while exercising and causes changes in subcutaneous adipose tissue. In adipose cells, irisin will stimulate the browning process in White Adipose Tissue to increase thermogenesis and lipolysis.

Change in Inflammatory Biomarkers and Adipose Tissue in BRCA1/2+ Breast Cancer Survivors Following a Yearlong Lifestyle Modification Program.

Breast cancer survivors who carry a genetic mutation for one of the BRCA genes often undergo surgically induced menopause a decade or more before the usual age of natural menopause. These women are at elevated risk for multiple negative health outcomes, including metabolic diseases, heart disease, and cancer recurrence. Effects of a 12-month commercially available web-based lifestyle program (Precision Nutrition) were tested on body composition and markers of inflammation in a randomized controlled trial. Participants (N = 35) were BRCA1/2+, breast cancer survivors, and had completed surgically induced menopause at age <45 years. Dual-energy X-ray absorptiometry was used to quantify body composition. Fasting blood samples were used to assay insulin, IL1β, IL6, IL8, and TNFα. At baseline, we observed relationships between insulin, TNFα, and IL6, and between biomarkers and adiposity. Insulin and subcutaneous adipose tissue levels significantly decreased following the intervention compared with the change in the control group. Compared with baseline, TNFα and total adipose tissue levels decreased significantly in the intervention group. The percent change in insulin levels was moderately correlated with the percent change in subcutaneous adipose tissue (r = 0.33). Change in adiposity was not related to change in TNFα or IL6. Women in the intervention group decreased levels of subcutaneous, but not visceral, adipose tissue. The change in subcutaneous adipose tissue was the main driver of change in insulin levels for the women in the intervention group. However, the change in body composition achieved by the Precision Nutrition program was not sufficient to alter biomarker levels of inflammation. Cancer Prev Res; 11(9); 545-50. ©2018 AACR.