Adipose Tissue Sites Research Articles

RNA editing landscape of adipose tissue in polycystic ovary syndrome provides insight into the obesity-related immune responses.

Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder with wide-ranging metabolic implications, including obesity. RNA editing, a post-transcriptional modification, can fine-tune protein function and introduce heterogeneity. However, the role of RNA editing and its impact on adipose tissue function in PCOS remain poorly understood. This study aimed to comprehensively analyze RNA-editing events in abdominal and subcutaneous adipose tissue of PCOS patients and healthy controls using high-throughput whole-genome sequencing (WGS) and RNA sequencing. Our results revealed that PCOS patients exhibited more RNA-editing sites, with adenosine-to-inosine (A-to-I) editing being prevalent. The expression of ADAR genes, responsible for A-to-I editing, was also higher in PCOS. Aberrant RNA-editing sites in PCOS adipose tissue was enriched in immune responses, and interleukin-12 biosynthetic process. Tumor necrosis factor (TNF) signaling, nuclear factor kappa B (NF-κB) signaling, Notch signaling, terminal uridylyl transferase 4 (TUT4), hook microtubule tethering protein 3 (HOOK3), and forkhead box O1 (FOXO1) were identified to be of significant differences. Differentially expressed genes (DEGs) in PCOS adipose tissue were enriched in immune responses compared with controls, and the DEGs between subcutaneous and abdominal adipose tissue were also enriched in immune responses suggesting the important role of subcutaneous adipose tissue. Furthermore, we identified the correlations between RNA editing levels and RNA expression levels of specific genes, such as ataxia-telangiectasia mutated (ATM) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) in inflammation pathways and ATM, TUT4, and YTH N6-methyladenosine RNA-binding protein C2 (YTHDC2) in oocyte development pathway. These findings suggest that RNA-editing dysregulation in PCOS adipose tissue may contribute to inflammatory dysregulations. Understanding the interplay between RNA editing and adipose tissue function may unveil potential therapeutic targets for PCOS management. However, further research and validation are required to fully elucidate the molecular mechanisms underlying these associations.

Impact of supplementation with native cerrado fruit oil on the composition of breast milk of lactating Wistar rats

The study aimed to evaluate the effect of baru oil (Dipteryx alata Vog) supplementation on maternal milk and offspring of female Wistar rats. Animals were divided into three groups (n = 12), supplemented with baru oil, soybean oil, or olive oil, at a daily dose of 1,000 mg/kg during pregnancy and lactation. The body weights and food intake of rats were measured weekly and analyzed. Milk collection was performed manually from the 12th to the 21st day of lactation. After weaning, rats and pups were euthanized after a 6-h fast. Blood was collected from the animals, five sites of adipose tissue were removed from each mother rat, and the mesenteric site was removed from the pups. It was observed that breast milk from the group supplemented with baru oil had higher concentrations of polyunsaturated and monounsaturated fatty acids, such as linoleic and oleic acids. However, there was no statistical difference between the group supplemented with Baru and soybean oil or olive oil group. Supplementation of the three types of oils did not interfere with body weight gain, animal consumption, serum parameters, liver weight, and adipose tissue sites. However, it showed antiatherogenic activity.

Dietary "Beigeing" Fat Contains More Phosphatidylserine and Enhances Mitochondrial Function while Counteracting Obesity.

Activation of mitochondrial function and heat production in adipose tissue by the modification of dietary fat is a promising strategy against obesity. However, as an important source of lipids for ketogenic and daily diets, the function of fats extracted from different adipose tissue sites was largely unknown. In this study, we illustrated the function of fats extracted from adipose tissues with different "beigeing" properties in the ketogenic diet and identified lipid profiles of fats that facilitate energy expenditure. We found that the anti-obesity effect of ketogenic diets was potentiated by using "beigeing" fat [porcine subcutaneous adipose tissue (SAT)] as a major energy-providing ingredient. Through lipidomic analyses, phosphatidylserine (PS) was identified as a functional lipid activating thermogenesis in adipose tissue. Moreover, invivo studies showed that PS induces adipose tissue thermogenesis and alleviates diet-induced obesity in mice. Invitro studies showed that PS promotes UCP1 expression and lipolysis of adipocytes. Mechanistically, PS promoted mitochondrial function in adipocytes via the ADCY3-cAMP-PKA-PGC1α pathway. In addition, PS-PGC1a binding may affect the stability of the PGC1α protein, which further augments PS-induced thermogenesis. These results demonstrated the efficacy of dietary SAT fats in diminishing lipid accumulation and the underlying molecular mechanism of PS in enhancing UCP1 expression and mitochondrial function. Thus, our findings suggest that as dietary fat, "beigeing" fat provides more beneficial lipids that contribute to the improvement of mitochondrial function, including PS, which may become a novel, nonpharmacological therapy to increase energy expenditure and counteract obesity and its related diseases.

Establishment of a Nomogram Based on Inflammatory Response-Related Methylation Sites in Intraoperative Visceral Adipose Tissue to Predict EWL% at One Year After LSG.

Laparoscopic sleeve gastrectomy (LSG) is considered as an effective bariatric and metabolic surgery for patients with severe obesity. Chronic low-grade inflammation of adipose tissue is associated with obesity and obesity-related complications. This study intends to establish a nomogram based on inflammatoryresponse-related methylation sites in intraoperative visceral adipose tissue (VAT) to predict excess weight loss (EWL)% at one-year after LSG. Based on EWL% at one-year after LSG, patients were divided into two groups: the satisfied group (group-A, EWL%≥50%) and the unsatisfied group (group-B, EWL%<50%). Next, we defined genes corresponding to the methylation sites in the 850 K methylation microarray as methylation-related genes (MRGs). We then took the intersection of MRGs and inflammatoryresponse-related genes. After that, inflammatoryresponse-related methylation sites were identified based on overlapping genes. Moreover, difference analysis was carried out to obtain inflammatoryresponse-related differentially methylated sites (IRRDMSs) between group-A and group-B. LASSO analysis was used to identify the hub methylation sites. Finally, we developed a nomogram based on the hub methylation sites. There were 26 patients in the study, with 13 in group-A and 13 in group-B. After data filtering and difference analysis, 200 IRRDMSs were identified (143 hypermethylated sites and 57 hypomethylated sites). Then, we identified three hub methylation sites (cg03610073, cg03208951, and cg18746357) by LASSO analysis and built a predictive nomogram (Area under the curve=0.953). The predictive nomogram based on three inflammatory-related methylation sites (cg03610073, cg03208951, and cg18746357) in intraoperative visceral adipose tissue can predict one-year EWL% after LSG effectively.

Parallel Study of Medodhara Kala and Abdominal Adipose Tissue with Special Reference to Sthoulya (Obesity)

Obesity which is neuroendocrine disorder seems to be common predisposing factor for almost all non-communicable diseases. This neuroendocrine disturbance causes multiple systemic disorders and finally Ayurhasa (reduction in longevity of life) by various means. Ayurveda mentioned eight pathophysiological conditions considered as Nindya (worse conditions). Atisthool (excessive weight) is one of these conditions due to improper Aahara (dietary habits), Vihar (sedentary life style) and changed sleep pattern. Apachita meda (improperly metabolized fat) deposited in Udara (abdomen). Medodharakala according to Ayurveda and abdominal linings bear several similar characteristics related to fat and Medodhatu deposition. Deterioration of functioning of Medodhara kala leads to deposition of Apachita meda leading to Sthoulya. In obesity, abdominal wall, space between organs stores much amount of adipose tissue (site of Meda deposition). So this article reveals with parallel study of Medodhara kala and abdominal adipose tissue to find out similarity.

Body Composition and Immunonutritional Status Impact Survival Outcomes after CD19 CAR T-Cell Therapy

Introduction: While CD19 chimeric antigen receptor T-cell therapy (CD19.CART) has altered the treatment landscape for multiple relapsed/refractory (r/r) B-cell malignancies, over 50% of patients ultimately relapse. To elucidate relapse mechanisms, previous studies have predominantly focused on disease- and treatment-related risk factors, while few studies have looked at systemic, host-intrinsic features. In this context, we recently demonstrated that an increase of metabolically high-risk adipose tissue sites, particularly visceral fat, impacts cytokine release syndrome onset and severity via IL-6 (Dos Santos & Rejeski et al, Haematologica 2022). We therefore hypothesized that body composition and nutritional status may also affect post-CAR-T survival outcomes. Methods: In this single-center, retrospective observational analysis, we studied patients receiving CD19.CAR-T for r/r B-cell malignancies between 01/2019 and 03/2022 in a real-world setting. We comprehensively analyzed the impact of immunometabolic host features including body composition (BC) measurements on clinical outcomes. We extracted psoas and skeletal muscle indices (PMI/SMI) as well as subcutaneous, visceral and epicardial adipose tissue (SAT/VAT/EAT) distributions from pre-lymphodepletion CT images. We further assessed the laboratory-based immuno-nutritional scores Glasgow Prognostic Score (GPS), CRP/Albumin Ratio and the Prognostic Nutritional Index (PNI). Efficacy outcomes were assessed according to Lugano criteria for B-NHL (LBCL, MCL) and according to MRD status for BCP-ALL. Durable responders were defined as reaching at least a partial remission (PR) or better by day 90, while non-responders had stable disease (SD), progressive disease (PD), or died due to treatment-related causes. Results: 66 consecutively treated patients were included in this analysis (53 LBCL, 9 MCL, 4 BCP-ALL). The following CD19.CART products were applied: axi-cel in 22 patients, tisa-cel in 25 patients and brexu-cel in 9 patients. Patients received a median of four prior treatment lines, which included a stem cell transplantation in 24 patients. The best 90-day overall response rate was 51.5%, with a complete remission rate of 40.9%. At a median follow-up time of 19 months, median PFS was 3.2 months and median OS 14 months. Based on the BC analysis, we found that CAR-responders displayed increased visceral adipose tissue deposits compared to CAR-non-responders (VAT: 120 vs. 67 cm2, p=0.01). Furthermore, immuno-nutritional scores (GPS, CRP/Albumin-Ratio, PNI) were significantly altered in non-responding patients. Next, we defined cut-off values for further analyses based on receiver operating characteristics for adipose tissue parameters and immunonutritional scores, and on optimal log-rank test separation for sarcopenia parameters. On univariate cox regression analysis, patients with VAT > 61.8 cm² exhibited a significantly lower risk of poor OS (Hazard Ratio [HR] = 0.35, 95% CI 0.18-0.70). Concomitantly, median PFS (5.1 vs. 1.9 months, p=0.04) and median OS (not-reached vs. 2.9 months, Fig. 1A) were significantly extended in patients with excess visceral adipose tissue. On the other hand, a SMI < 34.5 cm²/m², an indicator for sarcopenia, was associated with inferior OS (median 2.4 vs. 16.8 months, Fig. 1B). In a multivariate analysis adjusting for baseline CRP, LDH and ECOG performance status, increased VAT > 61.8 cm² was associated with improved clinical outcomes (high VAT: adjusted HROS: 0.28, 95% CI 0.13-0.59, p=<0.001). Conversely, sarcopenia significantly increased the risk of poor survival (low SMI: aHROS: 3.63, 95% CI 1.47-8.99, p=0.005). Moreover, malnutrition, defined by a PNI < 39.7, was associated with worse PFS and OS (low PNI: aHROS: 3.27, 95% CI 1.38-7.77, p=0.007). Conclusions: These findings highlight that body composition and nutritional status play a role as host-intrinsic prognostic factors in the context of CD19.CART. The link between visceral adipose tissue and improved survival suggests that the obesity paradox may extend to patients receiving T-cell based immunotherapies. If validated in future prospective studies, data on body composition and nutritional status may complement existing risk-stratification tools for patients receiving CD19-CART, and may lead to exercise- and diet-based interventional strategies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Retinoic acid induces the osteogenic differentiation of catadipose tissue-derived stromal cells from distinct anatomical sites.

Mesenchymal stromal cells-based regenerative orthopedic therapies have been used in cats as a promising and innovative therapeutic approach to enhance the repair of bone defects. Adipose tissue-derived stromal cells (ADSCs) can be obtained from two main sites-subcutaneous and visceral-with established differences regarding structure, composition, cell content, and functionality. However, in cats, to the best of the authors' knowledge, no studies have been conducted to compare the functional activity of the ADSCs isolated from the two sites, and the impact of these differences on the induced osteogenic potential. Additionally, retinoic acid has been recently regarded as a new osteogenic inducer within cells of distinct species, with undisclosed functionality on cat-derived cell populations. Thus, the present study aimed to evaluate the functional activity of ADSCs isolated from the subcutaneous and visceral adipose sites (SCAT and VAT, respectively) of the cat, as well as the effects of two osteogenic-inducing conditions-the classic dexamethasone, β-glycerophosphate and ascorbic acid-supplemented media (Dex +β+ AAM), and Retinoic Acid-supplemented media (RAM). The adipose tissue of subcutaneous and visceral origin was isolated, characterized, and ADSCs were isolated and grown in the presence of the two osteogenic-inducing conditions, and characterized in terms of proliferation, metabolic activity, morphology, and osteogenic activity. Our results demonstrated a distinct biological profile of the two adipose tissue sites regarding cell size, vascularization, and morphology. Further, osteogenic-induced ADSCs from both sites presented an increased expression of alkaline phosphatase activity (ALP) and cytochemical staining, as compared with control. Overall, RAM induced higher levels of ALP activity than Dex +β+ AAM, supporting an increased osteogenic activation. Additionally, VAT was the tissue with the best osteogenic potential, showing higher levels of ALP expression, particularly with RAM. In conclusion, different characteristics were found between the two adipose tissue sites-SCAT and VAT, which probably reflect the differences found in the functionality of isolated ADSCs from both tissues. Furthermore, for cat, VAT shows a greater osteogenic-inductive capacity than SCAT, particularly with RAM, which can be of therapeutic relevance for regenerative medicine applications.

C1QTNF3 is Upregulated During Subcutaneous Adipose Tissue Remodeling and Stimulates Macrophage Chemotaxis and M1-Like Polarization.

The adipose tissue undergoes substantial tissue remodeling during weight gain-induced expansion as well as in response to the mechanical and immunological stresses from a growing tumor. We identified the C1q/TNF-related protein family member C1qtnf3 as one of the most upregulated genes that encode secreted proteins in tumor-associated inguinal adipose tissue - especially in high fat diet-induced obese mice that displayed 3-fold larger tumors than their lean controls. Interestingly, inguinal adipose tissue C1qtnf3 was co-regulated with several macrophage markers and chemokines and was primarily expressed in fibroblasts while only low levels were detected in adipocytes and macrophages. Administration of C1QTNF3 neutralizing antibodies inhibited macrophage accumulation in tumor-associated inguinal adipose tissue while tumor growth was unaffected. In line with this finding, C1QTNF3 exerted chemotactic actions on both M1- and M2-polarized macrophages in vitro. Moreover, C1QTNF3 treatment of M2-type macrophages stimulated the ERK and Akt pathway associated with increased M1-like polarization as judged by increased expression of M1-macrophage markers, increased production of nitric oxide, reduced oxygen consumption and increased glycolysis. Based on these results, we propose that macrophages are recruited to adipose tissue sites with increased C1QTNF3 production. However, the impact of the immunomodulatory effects of C1QTNF3 in adipose tissue remodeling warrants future investigations.

Preliminary identification and analysis of differential RNA editing between higher and lower backfat thickness pigs using DNA-seq and RNA-seq data.

RNA editing is an essential post-transcriptional regulatory mechanism. However, few studies have investigated the functional RNA edits in the economic traits of livestock on a genome-wide scale. Pigs are one of the most important livestock species and their fat is the principal organ involved in the regulation of adipose deposition. Here, we used three full-sibling pairs, with each pair comprising a pig with higher backfat (BF) thickness and lower backfat thickness, to identify RNA editing events based on whole-genome and transcriptome sequencing data. A total of 60,903 non-redundant RNA editing sites with 59,472 (97.7%) A-to-G edits were detected using a revised bioinformatics pipeline. A specific sequence context with G preference was found one base downstream of the edited site, and the editing level was associated with the distribution of nucleotides across nearly sites. Moreover, the A-to-G editing sites mostly occurred in the pig-special short interspersed nuclear elements, Pre0_SS. Comparing the difference between pigs with higher BF and lower BF, we found 211 differentially edited sites (DESites). Functional enrichment analyses revealed a significant enrichment of genes containing DESites in terms of adipose deposition. The DESites located in the six adipose-related genes (SKP1, GSK3B, COL5A3, MDM4, NT5C2, and DENND2A) were selected as candidate RNA editing sites associated with adipose deposition, and thus require further evaluation. This study mined the potentially functional RNA editing sites in pig adipose tissue and indicated that RNA editing may play an important role in adipose deposition, which provides a new insight into the post-transcriptionally mediated regulation mechanism of fat development.

Fibroblast growth factor-21 improves insulin action in nonlactating ewes.

During metabolically demanding physiological states, ruminants and other mammals coordinate nutrient use among tissues by varying the set point of insulin action. This set point is regulated in part by metabolic hormones with some antagonizing (e.g., growth hormone and TNFα) and others potentiating (e.g., adiponectin) insulin action. Fibroblast growth factor-21 (FGF21) was recently identified as a sensitizing hormone in rodent and primate models of defective insulin action. FGF21 administration, however, failed to improve insulin action in dairy cows during the naturally occurring insulin resistance of lactation, raising the possibility that ruminants as a class of animals or lactation as a physiological state are unresponsive to FGF21. To start addressing this question, we asked whether FGF21 could improve insulin action in nonlactating ewes. Gene expression studies showed that the ovine FGF21 system resembles that of other species, with liver as the major site of FGF21 expression and adipose tissue as a target tissue based on high expression of the FGF21 receptor complex and activation of p44/42 extracellular signal-regulated kinase (ERK1/2) following exogenous FGF21 administration. FGF21 treatment for 13 days reduced plasma glucose and insulin over the entire treatment period and improved glucose disposal during a glucose tolerance test. FGF21 increased plasma adiponectin by day 3 of treatment but had no effect on the plasma concentrations of total, C16:0-, or C18:0-ceramide. Overall, these data confirm that the insulin-sensitizing effects of FGF21 are conserved in ruminants and raise the possibility that lactation is an FGF21-resistant state.

NLRP3 knockout enhances immune infiltration and inflammatory responses and improves survival in a burn sepsis model.

Although sepsis in burn patients is a major contributor to mortality, treatments are not always effective and underlying mechanisms have yet to be completely elucidated. NLRP3 inflammasome orchestrates burn-induced, inflammatory-driven pathophysiologic processes. Here, we determined the mechanism of NLRP3 inflammasome activation on bacterial clearance and mortality in burn sepsis. We obtained tissue and blood from 30 wild-type and 30Nlrp3-/- mice. Mice were subjected to a two-hit model of 25-30% TBSA scald burn followed by Pseudomonas aeruginosa wound infection 72hours after injury. We also obtained tissue from 34 adult burn patients (≥18years of age) with early (0-11days post-burn) and later (≥12days post-burn) surgical time-points and ten healthy controls. Murine studies indicated that Nlrp3-/- had 30% improved survival and bacterial clearance at the site of injury and is systemically relative to burn sepsis wild type. Greater macrophage and neutrophil infiltration occurred acutely after infection (12hours) to the site of injury and adipose tissue. This was followed by increased macrophage and neutrophil infiltration to lymphoid organs and liver beyond the acute phase (24 and 72hours). Interestingly, Nlrp3 ablation increased acute systemic inflammation (IL-6, TNF-α, IL-1β). Septic burn patients had persistently increased adipose NLRP3 by-product expression beyond the acute phase that was more pronounced in late-onset sepsis. Our findings suggest that Nlrp3genetic ablation enhanced acute tissue-specific inflammatory responsiveness. Likely, this occurs by paradoxically increasing acute immune infiltration and inflammation with a non-persistent response. Clinically, persistent NLRP3-mediated inflammation occurs in septic versus normal burn patients and potentially detrimentally impacts patient outcomes.

PSIV-14 Evidence for functional G-coupled protein receptors 43 and 120 in subcutaneous and intramuscular adipose tissue of Angus crossbred steers

Abstract We conducted experiments to demonstrate functional G-coupled protein receptor 43 (GPR43) and GPR120 in bovine intramuscular (i.m.) and subcutaneous (s.c.) adipose tissues. We hypothesized that media volatile fatty acids and long-chain fatty acids would affect cAMP concentrations differently in i.m. and s.c. adipose tissue, which would be dependent on GPR receptor populations in the adipose tissue sites. Fresh s.c. and i.m. adipose tissue from the 5th-8th longissimus thoracic rib muscle section of Angus crossbred steers (approximately 20 mo of age) was transferred immediately to 6-well culture plates containing 3 mL of KHB/Hepes/5 mM glucose. Samples were pre-incubated with 0.5 mM theophylline plus 10 μM forskolin for 30 min, after which increasing concentrations of acetate or propionate (0, 10–3, 10–2.3, and 10–3 M) in the absence or presence of 100 μM oleic acid (18:1 n-9) or 100 µM palmitic acid (16:0) were added to the incubation media. Acetate had no effect on forskolin-stimulated cAMP production in s.c. adipose tissue but decreased cAMP in i.m. adipose tissue (P &amp;lt; 0.05); this indicates a functional GPR43 receptor in i.m. adipose tissue. The combination of 10–2 M acetate and oleic acid decrease cAMP production in s.c. adipose tissue, consistent with GPR120 receptor activity, but oleic acid and palmitic acid attenuated the depression of cAMP production caused by acetate in i.m. adipose tissue. Palmitic acid depressed cAMP production in s.c. adipose tissue, and increased cAMP production in i.m. adipose tissue (P &amp;lt; 0.05). Propionate had no effect on cAMP production in s.c. or i.m. adipose tissue. These results provide evidence for functional GPR43 receptors in i.m. adipose tissue and GPR120 receptors in s.c. adipose tissue, both of which would suppress lipolysis. Further research may allow producers to increase marbling with exacerbating carcass fatness through pharmacological or dietary strategies.

Effects of Harvest Sites on Cryopreserved Adipose-Derived Stem Cells and ASC-Enriched Fat Grafts.

Enrichment of adipose-derived stem cells (ASCs) with fat grafts has demonstrated benefit for graft retention and histologic appearance. There is no consensus on the optimal harvest site for adipose-derived stem cells. This study aimed to investigate the effects of harvest sites on the characteristics of cryopreserved adipose-derived stem cells and the graft retention of cell-assisted lipotransfer. Lipoaspirates were harvested from 18 healthy volunteers who underwent liposuctions for body contouring. Twenty milliliters of lipoaspirates was, respectively, obtained from four sites, including the upper limb, abdomen, waist, and thighs, by the Coleman technique. Adipose-derived stem cells were ex vivo cultured and cryopreserved for four weeks. The biological characteristics of ASCs from four harvest sites were analyzed: MSC surface markers, cell proliferation, migration ability, and multipotential differentiation. The fat grafts were co-implanted with ASCs from four harvest sites and injected subcutaneously in mice. The ASC-enriched fat grafts were analyzed three months after transplantation. Cryopreserved ASCs from the abdomen and thighs maintained more significant cell proliferation, migration ability, and differentiation potential, compared with cells from the upper limb and waist. Moreover, we achieved better graft retention of cell-assisted fat grafts with cryopreserved ASC from the abdomen and thighs. The harvest site of adipose tissue affects the cellular activity and differentiation potential of cryopreserved ASCs. Improved understanding of harvest sites for ASCs can optimize the outcomes of cell-assisted fat grafts. Fat grafts enriched with cryopreserved ASCs from the abdomen or thighs are the optimal choices. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

White, brown, and bone marrow adipose tissue behavior in DHEA-induced PCOS mice

Introduction: To investigate the behavior of white, brown, and bone marrow adipose tissue (MAT) and the insulin resistance in a PCOS mice model. Methods Thirty-one female C57BL/6J mice were divided into four groups: two were treated with subcutaneous dehydroepiandrosterone (DHEA) implants and divided into normal and hypercaloric diet (HFD). Two were control and divided into normal and HFD. Presence of insulin resistance, growth, and adipocyte markers expression of white and brown adipose tissues and growth and inflammatory cytokines expression of bone marrow adipose tissue were evaluated. Results Hypercaloric diet groups presented higher total weight gain and huge growth in all fat sites, except bone marrow. They also demonstrated greater expression of adipocyte markers in sites of white adipose tissue. DHEA + HFD group showed more insulin intolerance than all other groups. DHEA shows to abrogate AdipoQ expression in all fatty tissues. Conclusions DHEA alone does not influence adipose tissue growth, but contributes to increased insulin resistance and influences the expression of adipokines. Proximal MAT showed different behavior from the other fat depot.

Depicting the Landscape of Adipose Tissue-Specific Macrophages and Their Immunometabolic Signatures during Obesity

Abstract Obesity is a widespread health condition, which can lead to the development of metabolic disorders, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease and cardiovascular diseases. Obesity is marked by the excessive deposition of fat in adipose tissue sites combined with chronic low-grade inflammation. Within this clinical setting, it is well established that adipose tissue macrophages exhibit prominent roles in regulating inflammation and metabolism. However, aside from these well-established roles, the involvement of microenvironmental cues as well as underlying cellular metabolism in driving immunological fate decisions within macrophages are poorly understood. Here we aim to map the different adipose tissue-derived macrophage subsets, together with their metabolic and functional profiles. Finally, we discuss their potential contribution during homeostasis and disease progression associated with obesity.

Genome-wide association study of blood lipids in Indians confirms universality of established variants.

Lipids foster energy production and their altered levels have been coupled with metabolic ailments. Indians feature high prevalence of metabolic diseases, yet uncharacterized for genes regulating lipid homeostasis. We performed first GWAS for quantitative lipids (total cholesterol, LDL, HDL, and triglycerides) exclusively in 5271 Indians. Further to corroborate our genetic findings, we investigated DNA methylation marks in peripheral blood in Indians at the identified loci (N = 233) and retrieved gene regulatory features from public domains. Recurrent GWAS loci-CELSR2, CETP, LPL, ZNF259, and BUD13 cropped up as lead signals in Indians, reflecting their universal applicability. Besides established variants, we found certain unreported variants at sub-genome-wide level-QKI, REEP3, TMCC2, FAM129C, FAM241B, and LOC100506207. These variants though failed to attain GWAS significance in Indians, but largely turned out to be active CpG sites in human subcutaneous adipose tissue and showed robust association to two or more lipid traits. Of which, QKI variants showed significant association to all four lipid traits and their designated region was observed to be a key gene regulatory segment denoting active transcription particularly in human subcutaneous adipose tissue. Both established and novel loci were observed to be significantly associated with altered DNA methylation in Indians for specific CpGs that resided in key regulatory elements. Further, gene-based association analysis pinpointed novel GWAS loci-LINC01340 and IQCJ-SCHIP1 for TC; IFT27, IFT88, and LINC02141 for HDL; and TEX26 for TG. Present study ascertains universality of selected known genes and also identifies certain novel loci for lipids in Indians by integrating data from various levels of gene regulation.

Effect of sex on glucose handling by adipocytes isolated from rat subcutaneous, mesenteric and perigonadal adipose tissue.

BackgroundAdult rat epididymal adipocytes are able to convert large amounts of glucose to lactate and glycerol. However, fatty acid efflux is much lower than that expected from glycerol levels if they were the product of lipolysis. Use of glucose for lipogenesis is limited, in contrast with the active glycolysis-derived lactate (and other 3-carbon substrates). In this study, we analyzed whether white adipose tissue (WAT) site and sex affect these processes.MethodsMature adipocytes from perigonadal, mesenteric and subcutaneous WAT of female and male rats were isolated, and incubated with 7 or 14 mM glucose during 1 or 2 days. Glucose consumption, metabolite efflux and gene expression of glycolytic and lipogenesis-related genes were measured.ResultsThe effects of medium initial glucose concentration were minimal on most parameters studied. Sex-induced differences that were more extensive; however, the most marked, distinct, effects between WAT sites, were dependent on the time of incubation. In general, the production of lactate was maintained during the incubation, but glycerol release rates increased with time, shifting from a largely glycolytic origin to its triacylglycerol (TAG) lipolytic release. Glycerol incorporation was concurrent with increased TAG turnover: lipolytic glycerol was selectively secreted, while most fatty acids were recycled again into TAG. Fatty acid efflux increased with incubation, but was, nevertheless, minimal compared with that of glycerol. Production of lactate and glycerol from glucose were maximal in mesenteric WAT.DiscussionFemale rats showed a higher adipocyte metabolic activity than males. In mesenteric WAT, gene expression (and substrate efflux) data suggested that adipocyte oxidation of pyruvate to acetyl-CoA was higher in females than in males, with enhanced return of oxaloacetate to the cytoplasm for its final conversion to lactate. WAT site differences showed marked tissue specialization-related differences. Use of glucose for lipogenesis was seriously hampered over time, when TAG turnover-related lipolysis was activated. We postulate that these mechanisms may help decrease glycaemia and fat storage, producing, instead, a higher availability of less-regulated 3-carbon substrates, used for energy elsewhere.

Harvesting, Isolation and Differentiation of Rat Adipose-Derived Stem Cells.

Adipose tissue is one of the most attractive sources of stem cells because it can be easily harvested and yields a greater stromal cell density. The multilineage potential of adiposederived stem cells (ADSCs) demonstrates their significant impact within the field of tissue engineering, with studies successfully demonstrating the ability to produce a range of tissue types. However, although a broad spectrum of applications has already been suggested, many important scientific and medical questions remain unanswered before the clinical application of ADSCs in humans. Importantly, clarification of the biology and identification of the differences of ADSCs from various areas of the body is required. In this continuous endeavor, research in rat models plays an important role in the development of new knowledge. A literature review was done to summarize all information regarding harvesting, isolation, expansion, cryopreservation and differentiation of rat ADSCs. A Wistar rat model was also used to describe harvesting sites of adipose tissue, and to characterize the ADSCs using Fourier-transform infrared (FT-IR) spectroscopy and phase contrast microscopy. To discuss all relevant considerations for harvesting, culture, differentiation and phenotypic characterization of ADSCs, to provide a comprehensive roadmap of this process, to identify the differences between ADSCs obtained from various adipose tissues of the rat, and to provide FT-IR spectroscopy marker bands that could be used as fingerprints to differentiate the types of adipose tissues.

Ganho de peso e alterações metabólicas em camundongos submetidos à dieta hiperlipídica

Objetivo: Avaliar a eficiência da dieta hiperlipídica na indução da obesidade e nas alterações do metabolismo da glicose e dos lipídeos, em camundongos C57BL/6.Materiais e Métodos: Utilizou-se 19 camundongos C57BL/6, divididos em grupo controle (dieta comercial; n=9) e experimental (dieta hiperlipídica; n=10). Foi mensurado o consumo de ração e ganho de peso durante 12 semanas, e calculado o Coeficiente de Eficiência Alimentar (CEA) e Índice Aterogênico. Foi realizado o Teste Oral de Tolerância à Glicose (TOTG), e construída a curva glicêmica, sendo verificada a área sobre a curva (AUC). Foram dissecados o fígado e os sítios de tecido adiposo (TA), feita análise histológica do fígado e TA epididimal, calculado o Índice de Adiposidade (IA%) e mensurada a concentração do colesterol total e frações, glicose e triglicerídeos séricos.Resultados: O grupo experimental apresentou menor consumo de ração (p&lt;0,001) e maior ganho de peso total (p=0,001) e CEA (p&lt;0,001). Observou-se aumento no TA epididimal (p&lt;0,001), retroperitoneal (p&lt;0,001), mesentérico (p=0,002) e perirrenal (p=0,012), gordura total (p&lt;0,001) e IA% (p&lt;0,001) no grupo experimental. O colesterol total foi maior no grupo experimental (p=0,025) e o HDL menor no controle (p=0,005). A área dos adipócitos do grupo experimental foi maior que do controle (p=0,049). Nos demais parâmetros não houve diferença significante entre os grupos.Conclusão: Este modelo induziu a obesidade em um curto período de tempo e promoveu aumento da adiposidade visceral, com dieta de baixo custo. São necessários outros estudos visando melhorar sua eficiência e alterar de forma completa os lipídeos sanguíneos e a glicemia nos camundongos C57BL/6.

Fat depot-specific differences of macrophage infiltration and cellular senescence in obese bovine adipose tissues.

Obesity is associated with the chronic inflammation and senescence of adipose tissues. Macrophage is a key mediator of chronic inflammation that infiltrates obese adipose tissue and stimulates metabolic disorders. However, the fat depot-specific differences of macrophage infiltration and senescence, especially the influence on intramuscular adipose tissue, have remained unclear. We investigated the fat depot-specific differences of macrophage infiltration and senescence in obese bovine adipose tissue from three different anatomical sites (subcutaneous, intramuscular and visceral). Macrophage infiltrations and crown-like structures were observed in visceral adipose tissue, although there were few macrophages in subcutaneous and intramuscular adipose tissues. The positive reaction of senescence marker SA-βgal activity was observed in visceral adipose tissue. In contrast, the activity of SA-βgal in subcutaneous and intramuscular adipose tissues were low. The expression of p53 gene, the master regulator of cellular senescence, in visceral adipose tissue was higher than that of subcutaneous and intramuscular adipose tissue. At the cellular level, p53 gene expression was negatively correlated with the size of subcutaneous adipocytes. In contrast, p53 gene expressions were positively correlated with the size of intramuscular and visceral adipocytes. These results indicate that anatomical sites of obese adipose tissue affect macrophage infiltration and the senescent state in a fat depot-specific manner.