Adipose Tissue Of Obese Women Research Articles

Evaluating the impact of polycyclic aromatic hydrocarbon bioaccumulation in adipose tissue of obese women

Polycyclic aromatic hydrocarbons (PAHs) are widespread across the environment and humans are unavoidably and constantly exposed to them. As lipophilic contaminants, these substances tend to accumulate in fatty tissues as adipose tissue and exposure to these endocrine disruptors has been associated with severe health hazards including prevalence and incidence of obesity. Previous studies have shown significantly higher concentrations of PAHs in adipose tissue compared to other human samples, such as urine and plasma, which are typically used for PAHs assessment. Therefore, conducting biomonitoring studies in adipose tissue is essential, although such studies are currently limited. In this study, the concentrations of 18 PAHs were measured in subcutaneous (scAT) and visceral adipose tissue (vAT) of 188 Portuguese obese females by high performance liquid chromatography (HPLC). The obtained results were then associated with the patient's data namely: 13 clinical, 4 social, and 42 biochemical parameters. Seventeen PAHs were present, at least, in one sample of both scAT and vAT, most of them with detection frequencies higher than 80%. Indeno [1,2,3-cd]pyrene (InP) was the only PAH never detected. Overall higher concentrations of PAHs were observed in scAT. Median concentrations of ∑PAHs were 32.2 ± 10.0 ng/g in scAT and 24.6 ± 10.0 ng/g in vAT. Thirty-six significant associations (7 with social, 18 with clinical, and 11 with biochemical parameters), including 21 Spearman's correlations were identified (12 positive and 9 negative correlations). Indicating the potential effects of PAHs on various parameters such as obesity evolution, body fat, number of adipocytes, total cholesterol, alkaline phosphatase, macrominerals, uric acid, sedimentation velocity, and luteinizing hormone. This study underscores the significance of biomonitoring PAH levels in adipose tissue and their potential effects on metabolic health. Further research is essential to fully comprehend the metabolic implications of PAHs in the human body and to develop strategies for obesity prevention and treatment.

Accumulation of organophosphorus pollutants in adipose tissue of obese women - metabolic alterations

Organophosphorus pesticides (OPPs) and organophosphate esters (OPEs) are organophosphorus compounds created as substitutes for persistent environmental pollutants, namely organochlorines pesticides and brominated flame retardants, respectively. However, there is evidence that organophosphorus compounds are also widespread across the environment and have adverse effects on biota. In humans, OPPs and OPEs were reported to be carcinogenic, neurotoxic, hepatotoxic, nephrotoxic, amongst others. As lipophilic compounds, these accumulate in fat tissues as adipose tissue. Yet biomonitoring studies and analytical methodologies to assess these compounds in the human body are scarce, particularly in adipose tissue. In this study, the presence of six OPPs and seven OPEs was determined in samples of subcutaneous adipose tissue (scAT) and visceral adipose tissue (vAT) from 188 adult obese women. OPPs and OPEs were quantified by gas chromatography (GC) flame photometric detection and confirmed in GC tandem mass spectrometry. The detection frequencies ranged between 0.5-1.6% and 48–53%, respectively for OPPs and OPEs. Organophosphorus pollutants were present in both adipose tissues and median concentrations were 0.008 ± 0.020 μg/g scAT and 0.009 ± 0.020 μg/g vAT. A total of 32 Spearman's correlations were found between organophosphorus pollutants concentrations in adipose tissue and several biochemical parameters (18 positive and 14 negative). Our results show that anthropometric and hormonal parameters, cholesterol, glycaemia, macrominerals, urea and sedimentation velocity might be influenced by the presence of these compounds. The presence of organophosphorus pollutants in the environmental and their possible effect on female metabolic processes is concerning. Particularly because presently OPEs usage is not controlled or limited by any regulation. More studies are needed to fully understand these pollutants behaviour and hazard effects on human health, biota, and the environment so control regulations can be drawn to prevent and lessen their effects.

The Relationship Between Menstrual Cycle Disorders In Obese Adolescents

Menstrual cycle disorders are the main symptom of anovulation, a phenomenon accompanied by decreased ovarian steroid secretion and production. Weight gain and an increase in adipose tissue in obese women, especially in the midsection, can disrupt the balance of steroid hormones such as androgens, estrogens, and sex hormone-binding globulins, which can affect the menstrual cycle in adolescents. The mechanism of obesity that is most often associated with menstrual cycle disorders. On that basis, this study aims to assess the relationship between insulin resistance and menstrual cycle disorders in obese adolescents. Method : This study used a cross-sectional design with comparisons where in this study the researchers compared the levels of the Homeostatic Model obese adolescent women who had normal menstrual cycles and abnormal menstrual cycles. Result : the group with abnormal menstrual cycles were found to be lower than those in the normal menstrual cycle group, but no significant difference was found. In addition, the abnormal menstrual cycle group were found to be lower but not significant. Conclusion : Obesity no significant relationship to the menstrual cycle in obese adolescent girls

Accumulation of Arachidonic Acid, Precursor of Pro-Inflammatory Eicosanoids, in Adipose Tissue of Obese Women: Association with Breast Cancer Aggressiveness Indicators.

While obesity is linked to cancer risk, no studies have explored the consequences of body mass index (BMI) on fatty acid profiles in breast adipose tissue and on breast tumor aggressiveness indicators. Because of this, 261 breast adipose tissue samples of women with invasive breast carcinoma were analyzed. Fatty acid profile was established by gas chromatography. For normal-weight women, major changes in fatty acid profile occurs after menopause, with the enrichment of long-chain polyunsaturated fatty acids (LC-PUFAs) of both n-6 and n-3 series enrichment, but a stable LC-PUFAs n-6/n-3 ratio across age. BMI impact was analyzed by age subgroups to overcome the age effect. BMI increase is associated with LC-PUFAs n-6 accumulation, including arachidonic acid. Positive correlations between BMI and several LC-PUFAs n-6 were observed, as well as a strong imbalance in the LC-PUFAs n-6/n-3 ratio. Regarding cancer, axillary lymph nodes (p = 0.02) and inflammatory breast cancer (p = 0.08) are more frequently involved in obese women. Increased BMI induces an LC-PUFAs n-6 accumulation, including arachidonic acid, in adipose tissue. This may participate in the development of low-grade inflammation in obese women and breast tumor progression. These results suggest the value of lifestyle and LC-PUFAs n-3 potential, in the context of obesity and breast cancer secondary/tertiary prevention.

Taurine supplementation associated with exercise increases mitochondrial activity and fatty acid oxidation gene expression in the subcutaneous white adipose tissue of obese women

To evaluate the effects of taurine supplementation associated or not with chronic exercise on body composition, mitochondrial function, and expression of genes related to mitochondrial activity and lipid oxidation in the subcutaneous white adipose tissue (scWAT) of obese women. A randomized and double-blind trial was developed with 24 obese women (BMI 33.1±2.9kg/m2, 32.9±6.3y) randomized into three groups: Taurine supplementation group (Tau, n=8); Exercise group (Ex, n=8); Taurine supplementation+exercise group (TauEx, n=8). The intervention was composed of 3g of taurine or placebo supplementation and exercise training for eight weeks. Anthropometry, body fat composition, indirect calorimetry, scWAT biopsy for mitochondrial respiration, and gene expression related to mitochondrial activity and lipid oxidation were assessed before and after the intervention. No changes were observed for the anthropometric characteristics. The Ex group presented an increased resting energy expenditure rate, and the TauEx and Ex groups presented increased lipid oxidation and a decreased respiratory quotient. Both trained groups (TauEx and Ex) demonstrated improved scWAT mitochondrial respiratory capacity. Regarding mitochondrial markers, no changes were observed for the Tau group. The TauEx group had higher expression of CIDEA, PGC1a, PRDM16, UCP1, and UCP2. The genes related to fat oxidation (ACO2 and ACOX1) were increased in the Tau and Ex groups, while only the TauEx group presented increased expression of CPT1, PPARa, PPARγ, LPL, ACO1, ACO2, HSL, ACOX1, and CD36 genes. Taurine supplementation associated with exercise improved lipid metabolism through the modulation of genes related to mitochondrial activity and fatty acid oxidation, suggesting a browning effect in the scWAT of obese women.

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

The Effects of the Dietary and Nutrient Intake on Gynecologic Cancers.

The contribution of diet to cancer risk has been considered to be higher in advanced countries than in developing countries. In this paper, I review the current issues (a review of the relevant literature), and the effects of the dietary and nutrient intake on three types of gynecologic cancer (cervical, endometrial and ovarian cancers). In cervical cancer, the most important roles of diet/nutrition in relation to cancer are prophylaxis and countermeasures against human papillomavirus (HPV) infection. The main preventive and reductive factors of cervical cancer are antioxidants, such as vitamin A, C, D and E, carotenoids, vegetables and fruits. These antioxidants may have different abilities to intervene in the natural history of diseases associated with HPV infection. For endometrial cancer, the increase in peripheral estrogens as a result of the aromatization of androgens to estrogens in adipose tissue in obese women and insulin resistance are risk factors. Thus, we must mainly take care to avoid the continuous intake of fat energy and sugar. In ovarian cancer, the etiology has not been fully understood. To the best of our knowledge, the long-term consumption of pro-inflammatory foods, including saturated fat, carbohydrates and animal proteins is a risk factor. The intake of acrylamide is also a risk factor for both endometrial and ovarian cancer. Most papers have been epidemiological studies. Thus, further research using in vitro and in vivo approaches is needed to clarify the effects of the dietary and nutrient intake in detail.

Heat Therapy Decreases Adipose Tissue Inflammation and Improves Insulin Signaling in Polycystic Ovary Syndrome

Passive hot water immersion promotes improvements in glucose control in humans, potentially by enhancing insulin sensitivity. In animal models, this improvement is mediated by increased heat shock protein (HSP) abundance, which inhibits production of inflammatory compounds that interfere with intracellular insulin signaling. The impact of repeated passive hot water immersion (termed ‘heat therapy’) on inflammation, HSP abundance, and insulin signaling in human adipose tissue have not been explored in an insulin‐resistant population such as obese women with Polycystic Ovary Syndrome (PCOS). While exercise training can improve insulin sensitivity in PCOS, novel treatments such as heat therapy are warranted as many individuals are unable to fully benefit from a traditional exercise program due to poor exercise tolerance or capacity. Therefore, the objective of this study was to examine changes in insulin signaling, inflammatory proteins, and HSPs in subcutaneous adipose tissue of obese women with PCOS undergoing an 8–10 week heat therapy intervention. Six obese women with PCOS (Age: 26±3y, BMI 42±2 kg·m2) underwent heat therapy, consisting of 30 × 1‐hr hot tub sessions over 8–10 weeks (3–4 per week) in 40.5°C water. Subcutaneous adipose tissue biopsies were collected from the periumbilical region at the start (Pre) and end (Post) of the chronic heat intervention. Tissue samples were analyzed using immunoblotting for HSP27, HSP70, and inflammatory proteins known to be impacted by HSPs and interfere with insulin signaling, including c‐Jun‐NH2‐terminal Kinase (JNK; inhibited by HSP70) and Inhibitor of Kappa B Kinase β (IKKβ; inhibited by HSP27). Additionally, a sub‐set of primary adipocytes in n=4 subjects were serum starved for 2 hours, then exposed to 1.2 nM insulin for 5 minutes for insulin signaling (p‐AKT) analysis using immunoblotting. All targets were quantified relative to loading control and expressed as a fold change from Pre to Post. Following heat therapy, insulin signaling (p‐AKT) increased in all subjects (4.1±2.0‐fold increase, p=0.19) despite no change in BMI (p=0.42). IKKβ significantly decreased (0.50 ± 0.06‐fold decrease, p=0.02) and JNK tended to decrease (0.48 ± 0.17‐fold decrease, p=0.09) after heat therapy. Abundance of HSP27 increased in all subjects (1.27 ± 0.14‐fold increase, p=0.18), while, conversely, HSP70 abundance significantly decreased (0.42±0.12‐fold decrease; p=0.03). In these preliminary data, heat therapy appears to promote improved insulin signaling in obese women with PCOS. This improvement is likely due to observed decreases in adipose tissue inflammation, potentially mediated in part by increased HSP27 abundance. Regular heat exposure has promise as a novel treatment in insulin‐resistant individuals to improve metabolic function. Heat can potentially be implemented as a complement or as a transition to exercise training to improve metabolic health, particularly in patient populations with severe metabolic dysfunction, mobility limitations, or low exercise tolerance.Support or Funding InformationSupported by American Heart Association Predoctoral Fellowship 16PRE27780085, Eugene & Clarissa Evonuk Memorial Fellowship, and the Ken and Kenda Singer Endowment Fund.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Green tea supplementation upregulates uncoupling protein 3 expression in severe obese women adipose tissue but does not promote weight loss

This study aims (i) to verify expression of the UCPs, PLIN1, PPARG2, and ADRB3 genes in the abdominal subcutaneous adipose tissue of obese women at baseline and after 8 weeks of supplementation with decaffeinated green tea extract, and (ii) to associate findings with clinical parameters. This is a longitudinal study during which 11 women with obesity grade III were submitted to supplementation with 450 mg of (–)-epigallocatechin gallate (EGCG) (intervention group); the control group consisted of 10 eutrophic women. Anthropometric parameters [weight, height, and body mass index (BMI)], resting metabolic rate (RMR, measured by indirect calorimetry), and gene expression (measured by real-time PCR, RT-qPCR) were determined before and after supplementation. After 8 weeks, clinical parameters and UCP1, PLIN1, PPARG2, and ADRB3 expression remained unaltered in the intervention group (p > .05). Genetic analysis also showed that the UCP3 gene was upregulated (p = .026), but its upregulation did not promote weight loss.

The adipokine tartrate-resistant acid phosphatase 5a in serum correlates to adipose tissue expansion in obesity

Purpose: Tartrate-resistant acid phosphatase (TRAP) exists as two isoforms, 5a and 5b. TRAP 5a is elevated in adipose tissue of obese women, interacts with pre-adipocytes and is linked to insulin-sensitive hyperplastic obesity when overexpressed in mice. The aim of this study was to investigate the relation between serum TRAP 5a, adiposity indices and metabolic syndrome risk markers in lean and obese women, using a newly developed TRAP 5a-specific ELISA.Materials and methods: A TRAP 5a sandwich ELISA was optimized using TRAP 5a-specific monoclonal antibodies and tested in sera of healthy males. TRAP 5a levels were quantitated in sera from healthy males and lean and obese women.Results: Serum TRAP 5a protein levels were lower in obese women in comparison with lean. In obese, but not in lean women, serum TRAP 5a correlated positively to % fat mass, BMI, waist- and hip circumference, waist-to-hip ratio and PAI, while no correlations to serum leptin, HOMA, glucose, insulin, FFA, HDL, TG, APO-A1 and APO-B were observed.Conclusions: TRAP 5a serum levels correlated positively to anthropometric obesity parameters but not to metabolic syndrome risk factors, indicating that serum TRAP 5a is associated with pathological adipose tissue expansion.

Depot-specific differences in fatty acid composition and distinct associations with lipogenic gene expression in abdominal adipose tissue of obese women

Cardiometabolic diseases are primarily linked to enlarged visceral adipose tissue (VAT). However, some data suggest heterogeneity within the subcutaneous adipose tissue (SAT) depot with potential metabolic differences between the superficial SAT (sSAT) and deep SAT (dSAT) compartments. We aimed to investigate the heterogeneity of these three depots with regard to fatty acid (FA) composition and gene expression. Adipose tissue biopsies were collected from 75 obese women undergoing laparoscopic gastric bypass surgery. FA composition and gene expression were determined with gas chromatography and quantitative real-time-PCR, respectively. Stearoyl CoA desaturase-1 (SCD-1) activity was estimated by product-to-precursor FA ratios. All polyunsaturated FAs (PUFA) with 20 carbons were consistently lower in VAT than either SAT depots, whereas essential PUFA (linoleic acid, 18:2n-6 and α-linolenic acid, 18:3n-3) were similar between all three depots. Lauric and palmitic acid were higher and lower in VAT, respectively. The SCD-1 product palmitoleic acid as well as estimated SCD-1 activity was higher in VAT than SAT. Overall, there was a distinct association pattern between lipid metabolizing genes and individual FAs in VAT. In conclusion, SAT and VAT are two distinct depots with regard to FA composition and expression of key lipogenic genes. However, the small differences between sSAT and dSAT suggest that FA metabolism of SAT is rather homogenous.

Transcriptomic Profiling of Adipose Tissue in Obese Women in Response to Acupuncture Catgut Embedding Therapy with Moxibustion.

Complementary and alternative medicine, such as Traditional Chinese Medicine, represents an efficient therapeutic option for obesity control. It was previously reported that acupuncture catgut embedding therapy (ACET) with moxibustion reduces body weight and reverts insulin resistance in obese women. This study aimed to evidence changes in adipokines and gene expression in adipose tissue that could explain the effects of ACET with moxibustion. Overweight/obese women were treated with ACET with moxibustion or sham acupuncture as control. Peripheral blood samples and fat biopsies were taken before and after intervention. Circulating adipokines (leptin, adiponectin, tumor necrosis factor alpha, and resistin) were quantified by enzyme-linked immunosorbent assay. Gene expression in adipose tissue was determined by cDNA microarray assays and assessed by quantitative reverse transcription real-time polymerase chain reaction. ACET with moxibustion did not modify circulating adipokines levels. However, correlations with anthropometric and biochemical parameters were affected. Interestingly, transcriptional changes in adipose tissue revealed the modulation of genes participating in homeostasis control, lipid metabolism, olfactory transduction, and gamma-aminobutyric acid signaling pathway. The effects of ACET with moxibustion on body weight and insulin resistance were associated with the regulation of biochemical events that are altered in obesity.

Expression of FBN1 during adipogenesis: Relevance to the lipodystrophy phenotype in Marfan syndrome and related conditions.

Fibrillin-1 is a large glycoprotein encoded by the FBN1 gene in humans. It provides strength and elasticity to connective tissues and is involved in regulating the bioavailability of the growth factor TGFβ. Mutations in FBN1 may be associated with depleted or abnormal adipose tissue, seen in some patients with Marfan syndrome and lipodystrophies. As this lack of adipose tissue does not result in high morbidity or mortality, it is generally under-appreciated, but is a cause of psychosocial problems particularly to young patients. We examined the role of fibrillin-1 in adipogenesis. In inbred mouse strains we found significant variation in the level of expression in the Fbn1 gene that correlated with variation in several measures of body fat, suggesting that mouse fibrillin-1 is associated with the level of fat tissue. Furthermore, we found that FBN1 mRNA was up-regulated in the adipose tissue of obese women compared to non-obese, and associated with an increase in adipocyte size. We used human mesenchymal stem cells differentiated in culture to adipocytes to show that fibrillin-1 declines after the initiation of differentiation. Gene expression results from a similar experiment (available through the FANTOM5 project) revealed that the decline in fibrillin-1 protein was paralleled by a decline in FBN1 mRNA. Examination of the FBN1 gene showed that the region commonly affected in FBN1-associated lipodystrophy is highly conserved both across the three human fibrillin genes and across genes encoding fibrillin-1 in vertebrates. These results suggest that fibrillin-1 is involved as the undifferentiated mesenchymal stem cells transition to adipogenesis but then declines as the developing adipocytes take on their final phenotype. Since the C-terminal peptide of fibrillin-1 is a glucogenic hormone, individuals with low fibrillin-1 (for example with FBN1 mutations associated with lipodystrophy) may fail to differentiate adipocytes and/or to accumulate adipocyte lipids, although this still needs to be shown experimentally.

Acute hyperlipidemia initiates proinflammatory and proatherogenic changes in circulation and adipose tissue in obese women

BackgroundObesity represents a high risk factor for the development of atherosclerosis and is associated with a low-grade inflammation and activation of immune cells. AimsThe aim of our study was to investigate the effect of a short-term lipid infusion on immune cells in blood and subcutaneous abdominal adipose tissue (SAAT) in obese women. MethodsSeven-hour intravenous lipid/control infusions were performed in two groups of women (n = 15, n = 10, respectively). Before and at the end of the infusion, SAAT and blood samples were obtained and relative content and phenotype of immune cells were analyzed using flow cytometry. Analysis of immune cell markers, inflammation and angiogenesis markers was performed in SAAT by RT-PCR and in plasma by immunoassays. ResultsRelative content of CD45+/14+ and CD45+/14+/16+ populations of monocytes was reduced in circulation by 21% (p = 0.004) and by 46% (p = 0.0002), respectively, in response to hyperlipidemia, which suggested the increased adhesion of these cells to endothelium. In line with this, the levels of sICAM and sVCAM in plasma were increased by 9.4% (p = 0.016), 11.8% (p = 0.008), respectively. In SAAT, the relative content of M2 monocyte/macrophages subpopulation CD45+/14+/206+/16+ decreased by 27% (p = 0.012) and subpopulations CD14+/CD206− and CD14/+TLR4+ cells increased (p = 0.026; p = 0.049, respectively). Intralipid infusion promoted an increase of mRNA levels in SAAT: RORC (marker of proinflammatory Th17 lymphocytes) by 43% (p = 0.048), MCP-1 (78%, p = 0.028) and VEGF (68.5%, p = 0.0001). ConclusionsAcute hyperlipidemia induces a proinflammatory and proatherogenic response associated with altered relative content of immune cells in blood and SAAT in obese women.

Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders.

We recently reported the presence of various cyclopropane fatty acids—among them, cyclopropaneoctanoic acid 2-hexyl—in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2-hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2-hexyl was determined by gas chromatography–mass spectrometry (GC–MS) in non-obese controls, obese patients, obese patients after a 3-month low-calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2-hexyl than controls. Switching obese individuals to a low-calorie (low-lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2-hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2-hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia-related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2-hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI.

GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women.

The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. Subcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, lipid and gene profiling were performed. In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, phosphatidylethanolamine methyl transferase (PEMT), decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum. The relevance of these findings to insulin resistance in humans is supported by published mouse studies, in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action and PEMT was required for adipocyte lipid storage. Thus in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.

Effect of lipid infusion on monocytes/macrophages in circulation and adipose tissue of obese women

Effect of lipid infusion on monocytes/macrophages in circulation and adipose tissue of obese women

Downregulation of complement C3 and C3aR expression in subcutaneous adipose tissue in obese women.

BackgroundThe central component of the complement system, C3, is associated with obesity, metabolic syndrome and cardiovascular disease however the underlying reasons are unknown. In the present study we evaluated gene expression of C3, the cleavage product C3a/C3adesArg and its cognate receptor C3aR in subcutaneous and omental adipose tissue in women.MethodsWomen (n = 140, 21–69 years, BMI 19.5–79 kg/m2) were evaluated for anthropometric and blood parameters, and adipose tissue gene expression.ResultsSubjects were separated into groups (n = 34–36) according to obesity: normal/overweight (≤30 kg/m2), obese I (≤45 kg/m2), obese II (≤51 kg/m2), and obese III (≤80 kg/m2). Overall, while omental expression remained unchanged, subcutaneous C3 and C3aR gene expression decreased with increasing adiposity (2-way ANOVA, p<0.01), with a concomitant decrease in SC/OM ratio (p<0.001). In subcutaneous adipose, both C3 and C3aR expression correlated with apoB, and apoA1 and inversely with waist circumference and blood pressure, while C3aR also correlated with glucose (p<0.05–0.0001). While omental C3aR expression did not correlate with any factor, omental C3 correlated with waist circumference, glucose and apoB (all p<0.05). Further, while plasma C3a/C3adesArg increased and adiponectin decreased with increasing BMI, both correlated (C3a negatively and adiponectin positively) with subcutaneous C3 and C3aR expression (p<0.05–0.001) or less).ConclusionsThe obesity-induced down-regulation of complement C3 and C3aR which is specific to subcutaneous adipose tissue, coupled to the strong correlations with multiple anthropometric, plasma and adipokine variables support a potential role for complement in immunometabolism.

Regional adipose tissue hormone/cytokine production before and after weight loss in abdominally obese women

ObjectiveTo compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss.Design and MethodsForty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: ~2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention.ResultsAdipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined. The intervention resulted in significant weight loss (−10.1 ±0.7 kg, P<0.001). At baseline, gene expression of adiponectin were higher (P<0.01), and gene expression and release of IL-6 were lower (both P<0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P<0.05 to P<0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P<0.05).ConclusionA 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity.

17β-Estradiol and Estradiol Fatty Acyl Esters and Estrogen-Converting Enzyme Expression in Adipose Tissue in Obese Men and Women

Obesity is associated with increased circulating 17β-estradiol (E₂), but less is known about E₂ concentrations in adipose tissue. In addition to E₂, adipose tissue synthesizes E₂ fatty acyl esters (E₂-FAE). The aim was to compare estrogen concentrations and expression of estrogen-converting enzymes in adipose tissue between severely obese men and women. Tissue samples were obtained during elective surgery in University Central Hospital in the years 2008 through 2011. We studied 14 men and 22 premenopausal women undergoing bariatric surgery and 10 control women operated for nonmalignant reasons. Paired samples were taken from abdominal sc and visceral adipose tissue and serum and analyzed for E₂ and E₂-FAE by fluoroimmunoassay and liquid chromatography-tandem mass spectrometry. mRNA expression of genes was analyzed by quantitative PCR. Compared with men, E₂ levels in sc adipose tissue in obese women were higher, along with higher relative mRNA expression of steroid sulfatase and 17β-hydroxysteroid dehydrogenases 1, 7, and 12. In men, E₂-FAE concentrations in adipose tissue were similar to E₂ but in women significantly lower compared with E₂. Adipose tissue E₂-FAE and serum E₂-FAE levels correlated positively in obese subjects. Serum E₂ did not significantly correlate with E₂ concentration or mRNA expression of genes in adipose tissue in obese men or women. The production of E₂ by the large adipose mass was not reflected by increased circulating E₂ concentrations in severely obese men or women. However, adipose tissue may contribute to concentrations of serum E₂-FAE.