Adipose Tissue Gene Expression Research Articles

Serglycin Is Involved in Adipose Tissue Inflammation in Obesity

Abstract Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn+/+ and Srgn−/− mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn+/+ and Srgn−/− mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn−/− mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn−/− compared with Srgn+/+ mice. Further, Srgn−/− mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.

Adipose tissue plays a major role in retinoic acid-mediated metabolic homoeostasis

ABSTRACT Retinoic acid (RA), a bioactive metabolite of vitamin A, has shown therapeutic effects in liver disease, and its effect in improving non-alcoholic fatty liver disease (NAFLD) is associated with the inhibition of adipogenesis in the white adipose tissue (WAT) and fatty acid oxidation induction in the liver. However, the major target organ of RA is unknown. We performed chronic administration of RA in high-fat diet (HFD)-induced NAFLD mice. Further, hepatic and adipose cells were used to study the direct effect of RA on lipid metabolism. In addition, qRT-PCR was performed to examine differential gene expression in mouse adipose tissue. RA administration ameliorated NAFLD in HFD-induced obese mice and increased mouse energy expenditure. Although RA had therapeutic effects on liver histology and lipid accumulation, it did not directly affect lipid metabolism in HepG2 cells. In contrast, RA reduced the weight of several adipose tissues and improved lipid accumulation in OP9 cells. In addition, RA upregulated genes responsible for fatty acid oxidation and thermogenesis in three different WATs. Our work suggests that the liver may not be the main target organ of RA during NAFLD treatment. WAT browning induced by RA may be the primary contributor towards the amelioration of NAFLD in HFD-induced obese mice.

Metabolite Changes After Metabolic Surgery - Associations to Parameters Reflecting Glucose Homeostasis and Lipid Levels.

AimsTo test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery.Materials and MethodsThis observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days).ResultsTwelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels.ConclusionsOur study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement.

2021 Canadian Surgery Forum: Virtual, online Sept. 21-24, 2021.

# 01. Design and validation of a unique endoscopy simulator using a commercial video game {#article-title-2} Procedural simulation has been shown to enhance early endoscopy training. In this proof of concept study, we aimed to show that a first-person shooter (FPS) video game with a novel in-house

PPAR-γ Gene Expression in Human Adipose Tissue Is Associated with Weight Loss After Sleeve Gastrectomy

BackgroundThe peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may regulate its expression and whether obese patients have changes in adipose tissue expression of PPAR-γor potential regulators such as miR-27. Thus, our aims were to analyze PPAR-γ and miR-27 expression in adipose tissue of obese patients, and to correlate their levels with clinical variables. Subjects and Methods.We included 43 morbidly obese subjects who underwent sleeve gastrectomy (31 of them completed 1-year follow-up) and 19 non-obese subjects. mRNA expression of PPAR-γ1 and PPAR-γ2, miR-27a, and miR-27b was measured by qPCR in visceral and subcutaneous adipose tissue. Clinical variables and serum adipokine and hormone levels were correlated with PPAR-γ and miR-27 expression. In addition, a systematic review of the literature regarding PPAR-γ expression in adipose tissue of obese patients was performed. ResultsWe found no differences in the expression of PPAR-γ and miR-27 in adipose tissue of obese patients vs. controls. The literature review revealed discrepant results regarding PPAR-γ expression in adipose tissue of obese patients. Of note, we described a significant negative correlation between pre-operative PPAR-γ1 expression in adipose tissue of obese patients and post-operative weight loss, potentially linked with insulin resistance markers. ConclusionPPAR-γ1 expression in adipose tissue is associated with weight loss after sleeve gastrectomy and may be used as a biomarker for response to surgery.

Reduced Body Fat and Epididymal Adipose Apelin Expression Associated With Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Weight Gain Prevention in High-Fat-Diet Fed Mice.

Raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] is a natural aromatic compound found in raspberries and other fruits. Raspberry ketone (RK) is synthetically produced for use as a commercial flavoring agent. In the United States and other markets, it is sold as a dietary supplement for weight control. The potential of RK to reduce or prevent excessive weight gain is unclear and could be a convergence of several different actions. This study sought to determine whether acute RK can immediately delay carbohydrate hyperglycemia and reduce gastrointestinal emptying. In addition, we explored the metabolic signature of chronic RK to prevent or remedy the metabolic effects of diet-induced weight gain. In high-fat diet (HFD; 45% fat)-fed male mice, acute oral gavage of RK (200 mg/kg) reduced hyperglycemia from oral sucrose load (4 g/kg) at 15 min. In HFD-fed female mice, acute oral RK resulted in an increase in blood glucose at 30 min. Chronic daily oral gavage of RK (200 mg/kg) commencing with HFD access (HFD_RK) for 11 weeks resulted in less body weight gain and reduced fat mass compared with vehicle treated (HFD_Veh) and chronic RK starting 4 weeks after HFD access (HFD_RKw4) groups. Compared with a control group fed a low-fat diet (LFD; 10% fat) and dosed with vehicle (LFD_Veh), glucose AUC of an oral glucose tolerance test was increased with HFD_Veh, but not in HFD_RK or HFD_RKw4. Apelin (Apln) gene expression in epididymal white adipose tissue was increased in HFD_Veh, but reduced to LFD_Veh levels in the HFD_RK group. Peroxisome proliferator activated receptor alpha (Ppara) gene expression was increased in the hepatic tissue of HFD_RK and HFD_RKw4 groups. Overall, our findings suggest that long term daily use of RK prevents diet-induced weight gain, normalizes high-fat diet-induced adipose Apln, and increases hepatic Ppara expression.

Pharmacological Approaches to Attenuate Inflammation and Obesity with Natural Products Formulations by Regulating the Associated Promoting Molecular Signaling Pathways.

Obesity is a public health problem characterized by increased body weight due to abnormal adipose tissue expansion. Bioactive compound consumption from the diet or intake of dietary supplements is one of the possible ways to control obesity. Natural products with adipogenesis-regulating potential act as obesity treatments. We evaluated the synergistic antiangiogenesis, antiadipogenic and antilipogenic efficacy of standardized rebaudioside A, sativoside, and theasaponin E1 formulations (RASE1) in vitro in human umbilical vein endothelial cells (HUVECs), 3T3-L1 preadipocytes respectively, and in vivo using a high-fat and carbohydrate diet-induced obesity mouse model. Orlistat was used as a positive control, while untreated cells and animals were normal controls (NCs). Adipose tissue, liver, and blood were analyzed after dissection. Extracted stevia compounds and green tea seed saponin E1 exhibited pronounced antiobesity effects when combined. RASE1 inhibited HUVEC proliferation and tube formation by suppressing VEGFR2, NF-κB, PIK3, and-catenin beta-1 expression levels. RASE1 inhibited 3T3-L1 adipocyte differentiation and lipid accumulation by downregulating adipogenesis- and lipogenesis-promoting genes. RASE1 oral administration reduced mouse body and body fat pad weight and blood cholesterol, TG, ALT, AST, glucose, insulin, and adipokine levels. RASE1 suppressed adipogenic and lipid metabolism gene expression in mouse adipose and liver tissues and enhanced AMP-activated protein kinase levels in liver and adipose tissues and in serum adiponectin. RASE1 suppressed the NF-κB pathway and proinflammatory cytokines IL-10, IL-6, and TNF-α levels in mice which involve inflammation and progression of obesity. The overall results indicate RASE1 is a potential therapeutic formulation and functional food for treating or preventing obesity and inflammation.

Anti-obesity Effect of Mulberry Anthocyanins in C57BL/6J Mice

Background: In this study, we evaluated the anti-obesity effects of purified mulberry anthocyanins using PB-600 macroporous resin (RPA), and investigated their effects on the weight of the body, liver, and epididymal white adipose tissue, lipid profiles, and mRNA gene expression for lipid metabolism in high-fat diet (HFD)-induced obese C57BL/6J male mice.<BR>Methods and Results: Four-week-old C57BL/6J mice (n = 12/group) were fed an HFD (HFD group) with RPA (HFD + RPA group, 5,000 ㎎/㎏/day, 761.85 ㎎· cyanidin 3-glucoside equivalent/g) for 12 weeks. Mice fed HFD showed increased body weight, insulin resistance, and serum and hepatic lipid levels. In comparison, the HFD + RPA group showed significantly lower body weight and fat mass with a decreasing food efficiency ratio than the HFD control mice. Additionally, the RPA group showed significantly lower levels of total cholesterol and blood glucose, decreased homeostatic model assessment insulin resistance (HOMA-IR) score, attenuated lipid accumulation, and decreased leptin secretion. Regarding the mRNA expression of genes related to anti-obesity and anti-inflammatory properties, RPA decreased the expression levels of PPARγ, FAS, IL-6, and TNFα, compared to the HFD control, while increased the CPT 1 expression levels increased.<BR>Conclusions: These results confirm that RPA, a purified mulberry anthocyanin has anti-obesity, and anti-inflammatory effects and could be used for functional and health-promoting activities, such as reducing obesity and insulin resistance at high doses in obese animals models.

Possible Involvement of Adipose Tissue in Patients With Older Age, Obesity, and Diabetes With SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19.

Aging, obesity, and diabetes are major risk factors for the severe progression and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically interacts with cell surface GRP78, which promotes the binding to and accumulation in ACE2-expressing cells. GRP78 was highly expressed in adipose tissue and increased in humans and mice with older age, obesity, and diabetes. The overexpression of GRP78 was attributed to hyperinsulinemia in adipocytes, which was in part mediated by the stress-responsive transcription factor XBP-1s. Management of hyperinsulinemia by pharmacological approaches, including metformin, sodium–glucose cotransporter 2 inhibitor, or β3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue. Environmental interventions, including exercise, calorie restriction, fasting, or cold exposure, reduced the gene expression of GRP78 in adipose tissue. This study provides scientific evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes. The management of hyperinsulinemia and the related GRP78 expression could be a therapeutic or preventative target.

PSVI-23 Depot- specific patterns of mRNA and miRNA gene expression in adipose tissue from Texel-cross and Suffolk lambs

Abstract Excess fat deposition is costly to the producer in terms of input and final product; it also usually does not occur equally across all adipose depots. Further examination is necessary to determine a correlation between varying gene expression and fatty acid composition in different tissue depots, and further, across different breeds. Texel-Suffolk (n = 5) and Suffolk-Suffolk (n = 4) lambs were finished to 203 d of age and used to compare both mRNA and microRNA (miR) gene expression changes between breed and among tissue depots. Seven different depots were harvested and snap-frozen from all nine lambs. The liver, longissimus muscle of the rib, kidney fat, mesenteric fat, omental fat, subcutaneous fat, and intermuscular fat were all harvested. Texel-sired lambs had greater (P &amp;lt; 0.05) flank streaking, quality grade, and weight of fat depots compared to Suffolk. Texel-cross lambs had higher (P &amp;lt; 0.05) oleic-to-stearic fatty acid ratio than Suffolk lambs in this study, displaying a breed difference concerning this desaturation ratio. Tissue and breed interactions were observed for oleic-to-stearic and palmitoleic-to-palmitic ratio differences (P &amp;lt; 0.05) depending on tissue type. Tissue and breed interactions were trending in various tissues concerning the expression of the gene, stearoyl-CoA desaturase-1(SCD-1). SCD-1 seemed to be upregulated (P &amp;lt; 0.10) in a multitude of tissues while others do not appear to be differentially expressed, dependent upon breed. Data showed an association between SCD-1 and mi-199a-3p among different tissue variations. This may suggest that adipose tissue is more complex than what is currently known. Lipogenic gene expression differed between tissue and adipose depots, and could potentially broaden targets that could aid in maximizing animal efficiency.

Plasma Fatty Acid Composition Was Associated with Apelin Gene Expression in Human Adipose Tissues.

Background Apelin is an adipokine with an intermediatory role in obesity and insulin resistance, which can be modified by dietary intake. Aims In this study, we aimed to determine the association of the plasma fatty acid composition with apelin plasma concentration and gene expression in visceral (VAT) and subcutaneous (SAT) adipose tissues. Methods In this cross-sectional study, we recruited 179 patients aged 19-75 years who were candidates for elective surgery. Through the surgery, SAT and VAT were collected to measure apelin gene expression. Anthropometric measurements, fasting blood samples, and dietary intakes were collected before surgery. Free fatty acids (FFAs) in fasting whole plasma were measured using gas chromatography with flame ionization detection. Linear regression models were used to estimate standardized β (STZ β) showing the association of individual and total FFAs with apelin gene expression after adjustment for potential confounding variables. Results In multivariable analysis, we observed a significant positive association of total plasma free fatty acids (FFAs) (STZ β = 0.241, P = 0.006), saturated fatty acid (SFA) (STZ β = 0.336, P < 0.001), and monounsaturated fatty acid (MUFA) (STZ β = 0.313, P < 0.001) concentrations with apelin gene expression from VAT after controlling for age, sex, body mass index, homeostatic model assessment for insulin resistance (HOMA-IR), physical activity, and energy intake. In the SFA family, there was a direct association with plasma concentration of myristic acid (STZ β = 0.372, P < 0.001), pentadecanoic acid (STZ β = 0.252, P = 0.002), and heptadecanoic acid (STZ β = 0.407, P < 0.001) with apelin mRNA expression in VAT. There was no significant association between FFAs and apelin plasma concentration and SAT mRNA levels. Conclusions In conclusion, circulating plasma FFAs, SFA, and MUFA had a positive association with apelin gene expression in VAT. It seems that plasma fatty acid composition may regulate apelin gene expression in VAT.

Atherosclerosis Pathways are Activated in Pericoronary Adipose Tissue of Patients with Coronary Artery Disease.

PurposePerivascular release of inflammatory mediators may accelerate coronary lesion formation and contribute to plaque instability. Accordingly, we compared gene expression in pericoronary adipose tissue (PCAT) in patients with advanced coronary artery disease (CAD) and non-CAD controls.Patients and MethodsPCAT samples were collected during coronary bypass grafting from CAD patients (n = 21) and controls undergoing valve replacement surgery, with CAD excluded by coronary angiography (n = 19). Gene expression was measured by GeneChip™ Human Transcriptome Array 2.0. Obtained list of 1348 transcripts (2.0%) that passed the filter criteria was further analyzed by Ingenuity Pathway Analysis software, identifying 735 unique differentially expressed genes (DEGs).ResultsAmong the CAD patients, 416 (30.9%) transcripts were upregulated, and 932 (69.1%) were downregulated, compared to controls. The top upregulated genes were involved in inflammation and atherosclerosis (chemokines, interleukin-6, selectin E and low-density lipoprotein cholesterol (LDL-C) receptor), whereas the downregulated genes were involved in cardiac ischaemia and remodelling, platelet function and mitochondrial function (miR-3671, miR-4524a, multimerin, biglycan, tissue factor pathway inhibitor (TFPI), glucuronidases, miR-548, collagen type I, III, IV). Among the top upstream regulators, we identified molecules that have proinflammatory and atherosclerotic features (High Mobility Group Box 2 (HMGB2), platelet-derived growth platelet (PDGF) and evolutionarily conserved signaling intermediate in Toll pathways (ESCIT)). The activated pathway related to DEGs consisted of molecules with well-established role in the pathogenesis of atherosclerosis (TFPI, plasminogen activator, plasminogen activator, urokinase receptor (PLAUR), thrombomodulin). Moreover, we showed that 22 of the altered genes form a pro-atherogenic network.ConclusionAltered gene expression in PCAT of CAD patients, with genes upregulation and activation of pathway involved in inflammation and atherosclerosis, may be involved in CAD development and progression.

The Same Metabolic Response to FGF21 Administration in Male and Female Obese Mice Is Accompanied by Sex-Specific Changes in Adipose Tissue Gene Expression.

The preference for high-calorie foods depends on sex and contributes to obesity development. Fibroblast growth factor 21 (FGF21) beneficially affects taste preferences and obesity, but its action has mainly been studied in males. The aim of this study was to compare the effects of FGF21 on food preferences and glucose and lipid metabolism in C57Bl/6J male and female mice with diet-induced obesity. Mice were injected with FGF21 or vehicle for 7 days. Body weight, choice between standard (SD) and high-fat (HFD) diets, blood parameters, and gene expression in white (WAT) and brown (BAT) adipose tissues, liver, muscles, and the hypothalamus were assessed. Compared to males, females had a greater preference for HFD; less WAT; lower levels of cholesterol, glucose, and insulin; and higher expression of Fgf21, Insr, Ppara, Pgc1, Acca and Accb in the liver and Dio2 in BAT. FGF21 administration decreased adiposity; blood levels of cholesterol, glucose, and insulin; hypothalamic Agrp expression, increased SD intake, decreased HFD intake independently of sex, and increased WAT expression of Pparg, Lpl and Lipe only in females. Thus, FGF21 administration beneficially affected mice of both sexes despite obesity-associated sex differences in metabolic characteristics, and it induced female-specific activation of gene expression in WAT.

Lower miR‐26a levels in breastmilk affect gene expression in adipose tissue of offspring

Breastmilk miRNAs may act as epigenetic regulators of metabolism and energy homeostasis in offspring. Here, we aimed to investigate the regulatory effects of miR-26a on adipose tissue development. First, the 3T3-L1 cell model was used to identify putative target genes for miR-26a. Then, target genes were analysed in adipose tissue of offspring from dams that supplied lower levels of breastmilk miR-26a to determine whether miR-26a milk concentration might have a long-lasting impact on adipose tissue in the progeny. In the in vitro model, both over- and under-expression of miR-26a were induced by transfecting into 3T3-L1 with miR-26a mimic and inhibitor. Array analysis was performed after induction of miR-26a to ascertain the impact on mRNA target genes and influence of differentiation status. Focusing on genes related to adipose tissue development, transfection with miR-26a mimic reduced the expression of Pten, Hmga1, Stk11, Rb1, and Adam17 in both pre- and mature adipocytes. Data mostly confirmed the results found in the animal model. After weaning, descendants of cafeteria-fed dams breastfed with lower levels of miR-26a displayed greater expression of Hmag1, Rb1, and Adam17 in retroperitoneal white adipose tissue in comparison with controls. Hence, alterations in the amount of miR-26a supplied through milk during lactation is able to alter the expression of target genes in the descendants and may affect adipose tissue development. Thus, milk miR-26a may act as an epigenetic regulator influencing early metabolic program in the progeny, which emerges as a relevant component of an optimal milk composition for correct development.

Spatial Regulation of Reactive Oxygen Species via G6PD in Brown Adipocytes Supports Thermogenic Function.

Reactive oxygen species (ROS) are associated with various roles of brown adipocytes. Glucose-6-phosphate dehydrogenase (G6PD) controls cellular redox potentials by producing NADPH. Although G6PD upregulates cellular ROS levels in white adipocytes, the roles of G6PD in brown adipocytes remain elusive. Here, we found that G6PD defect in brown adipocytes impaired thermogenic function through excessive cytosolic ROS accumulation. Upon cold exposure, G6PD-deficient mutant (G6PDmut) mice exhibited cold intolerance and downregulated thermogenic gene expression in brown adipose tissue (BAT). In addition, G6PD-deficient brown adipocytes had increased cytosolic ROS levels, leading to extracellular signal-regulated kinase (ERK) activation. In BAT of G6PDmut mice, administration of antioxidant restored the thermogenic activity by potentiating thermogenic gene expression and relieving ERK activation. Consistently, body temperature and thermogenic execution were rescued by ERK inhibition in cold-exposed G6PDmut mice. Taken together, these data suggest that G6PD in brown adipocytes would protect against cytosolic oxidative stress, leading to cold-induced thermogenesis.

Pioglitazone Reverses Markers of Islet Beta-Cell De-Differentiation in db/db Mice While Modulating Expression of Genes Controlling Inflammation and Browning in White Adipose Tissue from Insulin-Resistant Mice and Humans.

Obesity, insulin resistance, and type 2 diabetes contribute to increased morbidity and mortality in humans. The db/db mouse is an important mouse model that displays many key features of the human disease. Herein, we used the drug pioglitazone, a thiazolidinedione with insulin-sensitizing properties, to investigate blood glucose levels, indicators of islet β-cell health and maturity, and gene expression in adipose tissue. Oral administration of pioglitazone lowered blood glucose levels in db/db mice with a corresponding increase in respiratory quotient, which indicates improved whole-body carbohydrate utilization. In addition, white adipose tissue from db/db mice and from humans treated with pioglitazone showed increased expression of glycerol kinase. Both db/db mice and humans given pioglitazone displayed increased expression of UCP-1, a marker typically associated with brown adipose tissue. Moreover, pancreatic β-cells from db/db mice treated with pioglitazone had greater expression of insulin and Nkx6.1 as well as reduced abundance of the de-differentiation marker Aldh1a3. Collectively, these findings indicate that four weeks of pioglitazone therapy improved overall metabolic health in db/db mice. Our data are consistent with published reports of human subjects administered pioglitazone and with analysis of human adipose tissue taken from subjects treated with pioglitazone. In conclusion, the current study provides evidence that pioglitazone restores key markers of metabolic health and also showcases the utility of the db/db mouse to understand mechanisms associated with human metabolic disease and interventions that provide therapeutic benefit.

PAF signaling plays a role in obesity-induced adipose tissue remodeling.

Platelet-activating factor receptor (PAFR) activation controls adipose tissue (AT) expansion in animal models. Our objective was twofold: (i) to check whether PAFR signaling is involved in human obesity and (ii) investigate the PAF pathway role in hematopoietic or non-hematopoietic cells to control adipocyte size. Clinical parameters and adipose tissue gene expression were evaluated in subjects with obesity. Bone marrow (BM) transplantation from wild-type (WT) or PAFR-/- mice was performed to obtain chimeric PAFR-deficient mice predominantly in hematopoietic or non-hematopoietic-derived cells. A high carbohydrate diet (HC) was used to induce AT remodeling and evaluate in which cell compartment PAFR signaling modulates it. Also, 3T3-L1 cells were treated with PAF to evaluate fat accumulation and the expression of genes related to it. PAFR expression in omental AT from humans with obesity was negatively correlated to different corpulence parameters and more expressed in the stromal vascular fraction than adipocytes. Total PAFR-/- increased adiposity compared with WT independent of diet-induced obesity. Differently, WT mice receiving PAFR-/--BM exhibited similar adiposity gain as WT chimeras. PAFR-/- mice receiving WT-BM showed comparable augmentation in adiposity as total PAFR-/- mice, demonstrating that PAFR signaling modulates adipose tissue expansion through non-hematopoietic cells. Indeed, the PAF treatment in 3T3-L1 adipocytes reduced fat accumulation and expression of adipogenic genes. Therefore, decreased PAFR signaling may favor an AT accumulation in humans and animal models. Importantly, PAFR signaling, mainly in non-hematopoietic cells, especially in adipocytes, appears to play a significant role in regulating diet-induced AT expansion.

Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists.

Aldosterone exerts deleterious effects on the cardiovascular system and promotes adipose tissue expansion via mineralocorticoid receptor (MR) activation. We previously demonstrated that administration of steroidal mineralocorticoid receptor antagonists (MRA) in mice fed a moderate high-fat diet is able to reduce white adipose tissue (WAT) expansion, stimulate browning of WAT and activate interscapular brown adipose tissue (iBAT). Here, we aimed to compare the metabolic and adipose tissue-specific effects of the novel non-steroidal MRA finerenone (Fine) and spironolactone (Spiro) in a mouse model of very high-fat diet (HFD)-induced obesity. C57BL/6 J male mice were fed a 60% HFD containing or not Spiro or Fine for 12 weeks. WAT and iBAT morphology and adipose tissue gene expression analysis were assessed. After 12 weeks, both groups of mice showed similar weight gain compared to the HFD group. Histological and molecular analyses of WAT did not show significant differences among all experimental groups; differently, iBAT histological analysis revealed that Fine was able to increase recruitment of brown adipocytes in this depot, whereas mice treated with Spiro failed to elicit any iBAT response, as indicated by no changes in lipid droplets size and iBAT density, compared to HFD. Increased iBAT recruitment could explain, at least in part, the improved insulin resistance observed in mice treated with Fine, as shown by a significant reduction in homeostasis model assessment of insulin resistance (HOMA) index. These findings were confirmed by gene expression analysis of ucp-1, pgc1-α, and beta-3 adrenoreceptor (Adrb3) in iBAT, revealing significantly higher expression of these thermogenic genes in HFD + Fine group compared to HFD, whereas Spiro did not modify their expression. In summary, we demonstrated that, differently from Fine, Spiro did not induce iBAT recruitment. Our current study suggests that Fine, through its direct effects on iBAT, represents a promising pharmacologic tool to treat human metabolic diseases associated with adipose tissue dysfunctions.

Cecal Ligation and Puncture-Induced Sepsis Promotes Brown Adipose Tissue Inflammation Without Any Impact on Expression of Thermogenic-Related Genes.

Background and Aims: The negative effects of chronic low-level inflammation on adipose tissue physiology have been extensively demonstrated, whereas the effects of acute inflammation are less studied. Here, we aimed to investigate the effects of sepsis-induced acute inflammation on gene expression markers of brown and white adipose tissue functionality.Methods: Brown adipose tissue (BAT) and perirenal white adipose tissue (prWAT) gene expression markers were analyzed in cecal ligation and puncture (CLP)-induced sepsis mice model.Results: CLP-induced sepsis attenuated expression of adipogenesis-related genes, in parallel to increased Tnf, Il6, and Ltf gene expression in prWAT. In contrast, CLP-induced sepsis resulted in increased expression of pro-inflammatory genes (Il6, Ltf, and Lbp) in BAT, without affecting expression of genes encoding for thermogenic activity.Conclusion: Sepsis promotes both prWAT and BAT inflammation, associated with reduced adipogenesis-related gene expression in prWAT, without significant effects on BAT thermogenic genes.

Comparison of three aerobic exercise methods with different intensities on PPARγ2 gene expression in subcutaneous adipose tissue of male Wistar rats

Comparison of three aerobic exercise methods with different intensities on PPARγ2 gene expression in subcutaneous adipose tissue of male Wistar rats