Omental Fat Tissue Research Articles

Identifying Key Genes and Functionally Enriched Pathways of Diverse Adipose Tissue Types in Cattle.

Background: Fat is a tissue that not just stores energy and plays a protective role; it is also a vital endocrine organ that generates and integrates signals to influence metabolism. Meanwhile, the excessive accumulation of lipids in adipose tissue can lead to metabolic disturbance and diseases. To date, the complicated molecular mechanisms of bovine adipose tissue are still unknown. This study aimed to identify key genes and functionally enriched pathways in various adipose tissue types. Results: The RNAseq data of 264 samples were downloaded from Gene Expression Omnibus (GEO) and analyzed by weighted gene co-expression network analysis (WGCNA). We identified 19 modules that significantly associated with at least one adipose tissue type. The brown module from GSE39618 was most closely associated with intramuscular fat tissue, which contained 550 genes. These genes were significantly enriched in pathways that related to inflammation and disease, such as TNF signaling pathway, IL-17 signaling pathway, and NF-kappa B signaling pathway. The pink module (GSE39618) that contained 58 genes was most closely associated with omental fat tissue. The turquoise (GSE39618), blue (GSE116775), and yellow (GSE65125) module were most closely associated with subcutaneous fat tissue. Genes in these modules were significantly enriched in pathways related to fat metabolism, such as the PPAR signaling pathway, fatty acid metabolism and PI3K-Akt signaling pathway. At last, key genes for intramuscular fat (PTGS2 and IL6), omental fat (ARHGEF5 and WT1), and subcutaneous fat (KIT, QR6Q1, PKD2L1, etc.) were obtained and verified. In addition, it was found that IL10 and VCAM1 might be potential genes to distinguish adipose and muscle. Conclusion: The study applied WGCNA to generate a landscape of adipose tissue and provide a basis for identifying potential pathways and hub genes of different adipose tissue types.

Gastrointestinal dysbiosis caused by a lack of Paneth cells promotes diet-induced obesity and trafficking of inflammatory immune cells into adipose tissues.

Abstract Paneth cells regulate many aspects of gastrointestinal health through the antimicrobial products and cytokines they produce. Loss or defective Paneth cell function leads to dysbiosis and is one of the causes of Inflammatory Bowel Disease (IBD). The prevalence of obesity is growing in the general population and among recently diagnosed IBD patients, leading to the speculation that obesity increases IBD incidence, but the underlying mechanisms remain to be elucidated. We address whether gastrointestinal dysbiosis caused by a lack of Paneth cells influences obesity. Analysis of their fecal bacterial composition showed that Sox9ΔIEC mice, which lack Paneth cells due to a Sox9 gene deletion within the intestinal epithelium, have more Firmicutes bacteria (p<0.001) in their feces. These mice were then fed a high fat diet for 13 weeks. When Sox9ΔIEC mice were fed a high-fat diet, they exhibited increased bacterial dysbiosis. Furthermore, intestinal permeability measured by FITC-dextran absorption in vivo was increased (p<0.05) in Sox9ΔIEC mice. Finally, Sox9ΔIEC mice gained weight faster and ultimately became more obese than the wild-type mice and displayed impaired glucose tolerance (p<0.0001) indicating the presence of a metabolic disorder. The Sox9ΔIEC mice developed larger abdominal fats, which included increased numbers of inflammatory immune cells such as macrophages (p<0.05), neutrophils (p<0.05), and T cells (p<0.05). Interestingly, B cells were the most increased (p<0.0001) immune cell population in abdominal fat tissues. These results suggest a new role for Paneth cells as regulators of diet-induced obesity via their effect on gastrointestinal dysbiosis and immune cell infiltration of omental fat tissues.

Flaxseed Oil and Heated Flaxseed Supplements Have Different Effects on Lipid Deposition and Ileal Microbiota in Albas Cashmere Goats.

Simple SummaryWith the grassland desertification intensified, pasture carrying capacity decreased, and grass seasonal changed, stall-feeding fattening has become an effective means to protect the natural environment. The stall-feeding fattening increased the cashmere goats’ weight but reduced the meat quality and increased the saturated fatty acids content in muscle and fat tissue of cashmere goats. Supplementing flaxseed and flaxseed oil rich-in linolenic acid (ALA) to diet to improve meat quality is an effective nutritional regulation means. Previous research results of our team showed that compared to diet supplemented with flaxseed oil, added flaxseed increased linoleic acid biohydrogenation by reducing the Ruminobacter relative abundance and increasing the relative abundance of Prevotellaceae_UCG-001 and Fretibacterium in rumen, protected ALA away from biohydrogenation, and more n-3 polyunsaturated fatty acids entered the post-intestinal tract. Based on the previous research, this study explored whether the ALA flowing into the posterior intestine can reduce fat deposition and blood lipid by affecting intestinal microbiota. The results showed that adding flaxseed grain to diet decreased the growth performance, lipid deposition, and blood lipid content of goats by regulating the blood lipid-related enzyme activity, which positively associated with [Eubacterium]_coprostanoligenes_group, but negatively associated with unclassified_f_Peptostreptococcaceae, Intestinibacter, and Ruminococcus_2.The present study investigated the effect of flaxseed grain or flaxseed oil on ileal microbiota and lipid deposition of cashmere goats. Sixty kid goats (average body weight 18.6 ± 0.1 kg) were allocated to three treatments, fed for 90 days, with control treatment: basal diet (CON, total-mixed ration), experimental treatment: basal diet with added flaxseed oil (LNO), experimental treatment: basal diet with added heated flaxseed grain (HLS). The final body weight, body weight gain, the weight of kidney fat, omental fat, tail fat, and fat tissue, the activity of fatty acid synthetase, acetyl-coa carboxylase, and malic dehydrogenase, and the relative abundance (RA) of unclassified_f_Peptostreptococcaceae and Intestinibacter were remarkably higher in the LNO treatment than in the HLS treatment, but the [Eubacterium]_coprostanoligenes_group RA showed the opposite result. The content of triglyceride, cholesterol, and low-density lipoprotein cholesterol were significantly higher in the CON and LNO treatments than in the HLS treatment, while the hormone-sensitive lipase activity and the non-esterified fatty acid content showed the opposite result. In conclusion, the flaxseed grain is more efficient than flaxseed oil in ameliorating the blood lipid profiles and it is a potential product for decreasing the lipid deposition of cashmere goats.

The Value of Morphometric Measurements in Risk Assessment for Donor-Site Complications after Microsurgical Breast Reconstruction.

Microsurgical abdominally-based reconstruction is considered the gold standard in autologous breast reconstruction. Despite refined surgical procedures, donor-site complications still occur, reducing patient satisfaction and quality of life. Recent work has outlined the potential of morphometric measurements in risk assessment for postoperative hernia development. With rising demand for personalised treatment, the goal of this study was to investigate their potential in risk assessment for any donor site complication. In this retrospective cohort study, 90 patients were included who each received microsurgical breast reconstruction at the hands of one surgeon between January 2015 and May 2017. Donor-site complications formed the primary outcome and were classified according to Clavien–Dindo. Morphometric measurements were taken on a routinely performed computed tomographic angiogram. Complications occurred in 13 of the 90 (14.4%) cases studied. All patients who developed any type of postoperative donor site complication had a history of abdominal surgery. The risk of postoperative complications increased by 3% with every square centimetre of omental fat tissue (OR 1.03, 95% CI 1.00–1.06, and p-value = 0.022). Morphometric measurements provide valuable information in risk assessment for donor-site complications in abdominally-based breast reconstruction. They may help identify personalised reconstructive options for maximal postoperative patient satisfaction and quality of life.

Paneth cells regulate diet-induced obesity and trafficking of inflammatory immune cells into adipose tissues

Abstract Paneth cells regulate many key aspects of gastrointestinal health through the antimicrobial products and cytokines they produce. Loss or defective Paneth cell functions leads to dysbiosis and is one of the causes of Inflammatory Bowel Disease (IBD). The prevalence of obesity is growing in the general population and among recently diagnosed IBD patients, leading to the speculation that obesity increases IBD incidence, but the underlying mechanisms remain to be elucidated. We addressed whether Paneth cells of the small intestine play a role in the development of obesity. For this purpose, control wild-type C57BL/6 and Sox9ΔIEC mice, which lack Paneth cells due to Sox9 gene deletion within the intestinal epithelium (Sox9ΔIEC mice), were fed a high fat diet for 13 weeks. Though the consumption of food was similar between the 2 groups, weekly measurement of body weight showed that Sox9ΔIEC mice gained weight much faster and ultimately became more obese than the wild-type mice. The Sox9ΔIEC mice also developed larger abdominal fats, which included increased numbers of inflammatory macrophages (p<0.05) and neutrophils (p<0.05). Interestingly, B cells were the most increased (p<0.01) immune cells population in white fat tissues of Sox9ΔIEC mice. When compared to control mice, the Sox9ΔIEC mice displayed impaired glucose tolerance (p<0.0001) indicating that these mice also developed a metabolic disorder. Finally, the in vivo FITC-dextran permeability assay showed that Sox9ΔIEC mice on high-fat diet have increased intestinal permeability (p<0.05). These results suggest a new role for Paneth cells as regulators of diet-induced obesity via their impact on gut immune homeostasis and recruitment of immune cells into omental fat tissues.

P4406New hypothesis of the insulin resistance development: role of adipose-derived stem cell proliferation and adipogenesis

Abstract Background Obesity, remaining a topical issue of modern medicine, leads to development of latent inflammation and insulin resistance in adipose tissue with subsequent development of type 2 diabetes mellitus (T2DM). Among patients with obesity, patients with obesity and normal glucose tolerance (NGT) are often encountered. In our study we have tested the hypothesis that low proliferative potential of adipose derived stromal cells (ADSC) associates with reduced formation of new fat depots, excess accumulation of fat in the functional adipocytes and their hypertrophy, resulting in fat inflammation and insulin resistance. Methods We screened two groups of obese patients with or without T2DM, matched for BMI, age, and duration of obesity to test the hypothesis that hypertrophy and decreased renewal of adipocytes may underlie transition from obesity to T2DM. All patients were matched for carbohydrate metabolism (fasting blood glucose level, glycated hemoglobin, HOMA-IR index and M-index). The subcutaneous and omental fat tissue biopsies were obtained during bariatric surgery from obese individuals with or without T2DM. The morphology and immunophenotype of subcutaneous and omental fat was assessed in frozen tissue sections. ADSC were isolated from both types of fat tissue biopsies and screened for morphology, proliferative potential and inflammatory status. Results The non-diabetic patients had normal carbohydratemetabolism andmoderate insulin resistancemeasured byHOMA-IR and hyperinsulinemic clamp (M-index),while T2DM patientswere extremely insulin resistant by both indexes. The average size of diabetic adipocytes was higher than that of non-diabetic in both subcutaneous and omental fat tissues, indicating adipocyte hypertrophy in T2DM. We have shown that ADSC from T2DM patients had significantly higher level of inflammation. According to measurement of p62 expression and LC3 modification we can say that ADSC from T2DM patients have less autophagy level compare with ADSC from NGT patients. Immunohistochemistry have shown that patients with T2DM have much more infiltration of CD68+-cells in subcutaneous and omental adipose tissue and immunophenotype (balance of M1-M2 macrophages) of adipose tissue at this patients shift toward inflammatory state. Conclusion These results suggest that decreased proliferation and increased hypertrophy of diabetic ADSC may lead to reduced insulin sensitivity via increased inflammation mediated by M1-macrophages and JNK1/2 pathway. Acknowledgement/Funding This work was supported by RSF grant #17-15-01435

Differential circulating and visceral fat microRNA expression of non-obese and obese subjects

Altered microRNA (miRNA) expression is associated with the pathophysiology of obesity; however, little is known about the miRNAs commonly dysregulated in the blood and visceral fat tissue of obese patients. This study compared the circulating and visceral fat miRNA expression in subjects with and without obesity. For the circulating miRNA study, 20 healthy control and 30 obese subjects were recruited. For the tissue miRNA expression study, omental fat tissue was collected in ten female subjects each in the control and obese groups. MiRNA expression was measured by TaqMan low-density arrays. Metabolic risk factors were measured. Target genes for selected miRNAs were analyzed using informatics tools and a functional network map was constructed. 11 miRNAs were down-regulated (miR-133a, -139-5p, -15b, -26a, -301, -30b, -30c, -374, -451, -570, and -636), and one was up-regulated (miR-155) in both depots in obese subjects. These miRNAs had significant associations with BMI, waist circumference, and fat mass. Among them, miR-15b, miR-26a, miR-301, miR-30b, and miR-30c had more predicted obesity-related target genes than other miRNAs. In particular, miR-15b had numerous target genes associated with adipogenesis, mammalian target of rapamycin (mTOR) signaling, diabetes and insulin resistance, and mitochondrial function. It is suggested that the miRNA alteration in the serum and visceral fat has pathophysiological implications for obesity. Our study identified dysregulated miRNAs that may be novel therapeutic targets to combat obesity.

Low proliferative potential of adipose-derived stromal cells associates with hypertrophy and inflammation in subcutaneous and omental adipose tissue of patients with type 2 diabetes mellitus

BackgroundObesity and type 2 diabetes mellitus (T2DM) are among the most important morbidity factors. In this study we tested the hypothesis that low proliferative potential of adipose derived stromal cells (ADSC) associates with reduced formation of new fat depots, excess accumulation of fat in the functional adipocytes and their hypertrophy, resulting in fat inflammation and insulin resistance. MethodsWe screened two groups of obese patients with or without T2DM, matched for BMI, age, and duration of obesity to test the hypothesis that hypertrophy and decreased renewal of adipocytes may underlie transition from obesity to T2DM. All patients were matched for carbohydrate metabolism (fasting blood glucose level, glycated hemoglobin, HOMA-IR index and M-index). The subcutaneous and omental fat tissue biopsies were obtained during bariatric surgery from obese individuals with or without T2DM. The morphology and immunophenotype of subcutaneous and omental fat was assessed in frozen tissue sections. ADSC were isolated from both types of fat tissue biopsies and screened for morphology, proliferative potential and inflammatory status. ResultsThe non-diabetic patients had normal carbohydrate metabolism and moderate insulin resistance measured by HOMA-IR and hyperinsulinemic clamp (M-index), while T2DM patients were extremely insulin resistant by both indexes. The average size of diabetic adipocytes was higher than that of non-diabetic in both subcutaneous and omental fat tissues, indicating adipocyte hypertrophy in T2DM. Both these tissues contained higher level of macrophage infiltration and increased M1-like to M2-like ratio of macrophage subpopulations, suggesting increased fat inflammation in T2DM. This was confirmed by increased activatory phosphorylation of stress-induced JNK1/2 in diabetic ADSC. ConclusionThese results suggest that blunted proliferation and increased hypertrophy of diabetic ADSC may lead to reduced insulin sensitivity via increased inflammation mediated by M1 macrophages and JNK1/2 pathway.

The micromass formation potential of human adipose-derived stromal cells isolated from different various origins

BackgroundAdult stem cells appear to be a promising subject for tissue engineering, representing an individual material for regeneration of aged and damaged cells. Especially adipose derived stromal cells (ADSC), which are easily to achieve, allow an encouraging perspective due to their capability of differentiating into miscellaneous cell types. Here we describe the in vitro formation of human subcutaneous, visceral and omental ADSC micromasses and compare their histological attributes while being cultivated on collagen membranes.MethodsSubcutaneous, visceral and omental fat tissue derived cells were isolated and processed according to standard protocols. Positively stained cells for CD13, CD44 and CD90 were cultivated on agarose in order to study micromass formation using a special method of cell tracking. Stained paraffin-embedded micromasses were analysed morphologically before and after being plated on collagen membranes.ResultsThe micromass formation process was similar in all three tissue types. Subcutaneous fat tissue derived micromasses turned out to develop a more homogeneous and compact shape than visceral and omental tissue. Nevertheless all micromasses adhered to collagen membranes with visible spreading of cells. The immune histochemical (IHC) staining of subcutaneous, visceral and omental ADSC micromasses shows a constant expression of CD13 and a decrease of CD44 and CD 90 expression within 28 days. After that period, omental fat cells don’t show any expression of CD44.ConclusionIn conclusion micromass formation and cultivation of all analysed fat tissues can be achieved, subcutaneous cells appearing to be the best material for regenerative concepts.

A huge Morgagni hernia with compression of the right ventricle

A 21 year old male with no relevant medical history presented to our Institution for further assessments of a right paracardiac mass founded on a chest X-ray. Chest computed tomography revealed a wide median defect of the diaphragm at the level of xiphoid process of the sternum, with the herniation of omental fat tissue in the mediastinum. Cardiac magnetic resonance confirmed the presence of a huge hernia originating from the foramen of Morgagni (sterno-costal hiatus), displacing the heart leftwards and posteriorly and compressing the right ventricle (RV), giving to it a tubular shape.The signal characteristics were typical of fat tissue, with hyperintense signal in T1 and T2 weighted black blood images and homogeneus signal suppression on STIR T2 black blood images. Short axis real time cine images, performed during deep inspiration, showed an early diastolic ventricular septal bounce, with flattening of the interventricular septum during mid-late diastole: they represented signs of diastolic dysfunction of the right ventricle, resembling a sort of “pseudo-constrictive” pathophysiological model. The patient was thus referred to surgical repair of the diaphragmatic defect.

Testosterone increases CCL-2 expression in visceral adipose tissue from obese women of reproductive age

ContextHyperandrogenic states and obesity in women are associated with insulin-resistance. Androgens reduce glucose uptake in adipose cells and increase TNFα production in peripheral monocytes. Inflammatory cytokines have a known detrimental effect on insulin resistance. The aim of the present study was to explore the role of testosterone in local cytokine production in visceral adipose tissue from women of reproductive age. DesignTwenty-four women 18–40 years old, undergoing elective abdominal surgery for benign and non-inflammatory conditions, were recruited for the study. Women with clinical hyperandrogenism, diabetes, hepatic or renal dysfunction, hypothyroidism, BMI> 40 or drugs known to interfere with hormonal levels or fat metabolism were excluded. Women were classified into two groups according to BMI, non-obese (NO; BMI < 30) and obese (O; BMI 30–40). A basal blood sample was drawn at the time of surgery for the measurement of glucose, insulin, total testosterone, lipid profile and circulating CCL-2, IL-6 and total adiponectin. Omental fat tissue (10 g) was obtained in all women. Samples of 300 mg of minced adipose tissue were incubated with vehicle (CTL) or testosterone (T) 10−9 M to 10−6 M for 24, 48 or 72 h. CCL-2, IL-6, TNFα, androgen Receptor (AR) mRNA levels were measured by Real Time quantitative polymerase chain reaction (qPCR) and normalized to GAPDH expression. Secretion of CCL-2 and IL-6 was measured in conditioned media by ELISA. ResultsExpression of CCL-2 and IL-6 at 24 h in CTLs was significantly higher in the obese group compared to the non-obese group (2.81 ± 0.43 fold for CCL-2; p = 0.005 and 3.26 ± 0.73 fold for IL-6; p = 0.03). At 48 and 72 h there were no differences between both groups in any of the markers. In the total group without T stimulation (CTL) there were significant correlations between: TNFα expression at 24 h and BMI (r = 0.708; p = 0.005), TGC levels (r = 0.904; p = 0.004), total Cholesterol (r = 0.904; p = 0.0046) and IL-6 expression at 24 h (r = 0.642; p = 0.015). CCL-2 expression at 24 h was correlated with BMI (r = 0.637; p = 0.007) and TGC levels (r = 0.700; p = 0.02). Stimulation with T 10−6 M for 72 h produced an increase in CCL-2 expression, which was significantly larger in the obese group compared to the non-obese group (2.04 ± 0.44 in obese vs 0.82 ± 0.11 in non-obese; p = 0.015). Moreover, in the whole group there was a positive correlation between CCL-2 expression in T-treated tissues (10−6 M 72 h) and BMI (r = 0.514; p = 0.017). Cytokine determinations followed the same pattern as mRNA but without significant differences. ConclusionsTestosterone increases CCL-2 expression in visceral adipose tissue from obese women of reproductive age. This response is associated to BMI. These results show new possible mechanisms connecting androgens to insulin resistance and chronic inflammation.

Radiographic and Ultrasonographic Findings in Three Surgically Confirmed Cases of Small Intestinal Ischemia Related to Mesenteric Volvulus or Intestinal Torsion in Dogs

This case report describes the radiographic and ultrasonographic findings of three surgically confirmed cases of mesenteric volvulus or intestinal torsion in dogs. In all three cases, ultrasonographic findings included segmental ileus and absent or markedly reduced peristalsis of the affected small intestine, and partial loss of wall layering with increased overall echogenicity of the intestinal wall, but with normal to mildly increased wall thickening. No blood flow was detected in the affected small intestinal wall when assessed with colour Doppler. A moderate amount of peritoneal effusion was also detected with hyperechoic omental and mesenteric fat tissue throughout the peritoneal cavity. Few reports describe ultrasonographic findings of small intestinal ischemia in small animals. In all three cases presented here, ultrasound was helpful in demonstrating typical intestinal wall changes and helped to obtain the correct diagnosis of ischemic disease of the small intestine.

Features of omental adipose tissue in endometrial cancer patients with 'standard' or 'metabolically healthy' obesity: associations with tumor process characteristics.

PurposeAdipose tissue products may contribute to endometrial cancer (EC) initiation and further growth that encourages the analysis of this issue in patients with different obesity phenotypes.Methods/patientsOmental fat depot characteristics were studied in EC patients (n = 57) with “standard” (SO) or “metabolically healthy” (MHO) obesity. Collected omental samples were evaluated by immunohistochemistry /IHC/ for brown fat marker UCP1, CYP19 (aromatase) and macrophage infiltration markers (CD68, CD163, crown-like structures/CLS) expression. Total RNA extracted from the same samples was investigated for UCP1, CYP19, PTEN and adipokine omentin mRNA.ResultsImmunohistochemistry data revealed a statistically significant increase in aromatase and CD68 expression and tendency to increase of UCP1 expression in SO patients’ omental fat compared to samples obtained from MHO patients. Additionally, positive correlation of EC clinical stage with UCP1 protein and its mRNA content in omental fat was pronounced in MHO as well as SO group, while with omentin mRNA it was discovered only in patients with SO. An inclination to the correlation with better tumor differentiation was seen for UCP1 and CD68 protein expression in patients with MHO and with worse (high grade) differentiation—for CD68 expression in the group with SO.ConclusionsIn aggregate, this suggests that obesity phenotype has significant impact on omental fat tissue characteristics which is related to the clinical course of EC and may have practical consequences.

Hyperglycemia-induced changes in resistin gene expression in white adipose tissue in piglets

Abstract Previous data strongly indicated that resistin, an adipocyte-derived signalling peptide, plays an important role in metabolism and glucose homeostasis. Thus, the aim of the present study was to examine changes in synthesis and concentration of resistin in white adipose tissue in response to hyperglycemia in piglets. In order to develop hyperglycemia, piglets (10-week-old, Polish Landrace fatteners, female) received intraperitoneal (ip) injection of 150 mg streptozotocin (HI, n=6) or 60 mg synthetic glucocorticoid (HII, n=6). An injection of NaCl physiological saline was used as a control (n=6). Plasma resistin level was significantly higher in HII group compared with the control, while no difference was observed in HI. In epicardial adipose tissue (EAT ) the resistin mRNA level significantly increased whereas the opposite effect was observed for omental fat tissue (OAT ) in both experimental groups. Additionally, the resistin concentration did not change in EAT ; however, it was decreased in omental adipose tissue in response to hyperglycemia. The results obtained indicate that activity of resistin strongly depends on glycemic status as well as adipose tissue localization.

Primary Omental Pregnancy: Successful Laparoendoscopic Single-site Partial Omentectomy After Diagnosis by Diffusion-weighted Magnetic Resonance Imaging

A 34-year-old, gravida 2, para 0 woman was referred after 8 weeks of amenorrhea. Serum b-human chorionic gonadotropin value was 828 mIU/mL. Diffusion-weighted magnetic resonance imaging (MRI) [1] showed a hematoma-like mass with heterogeneous signal intensities, adjacent to the omental fat, in the retrovesical space, along with corpus lutein cyst of left ovary (Fig. 1, A and B). Emergency laparoendoscopic single-site (LESS) [1] partial omentectomy was performed because of difficult dissection of the firmly attached gestational mass from the omental tissue (Fig. 1C). Histopathologic examination of the excised specimen confirmed primary omental pregnancy by showing the chorionic villi with direct invasion of trophoblast to the omental fat tissue (Fig. 1D). Primary omental pregnancy, in which the fertilized ovum directly implants into the omental tissue [2], is a less common form of abdominal pregnancy [3]. Precise preoperative evaluation by diffusion-weighted MRI accelerates the successful minimally invasive management by LESS surgery.

Differential aromatase (CYP19A1) expression in omental and subcutaneous fat tissue in women with or without metabolic syndrome

Differential aromatase (CYP19A1) expression in omental and subcutaneous fat tissue in women with or without metabolic syndrome

Adiponectin Expression in Liver, Omental Fat, and Peripheral Circulation in Morbidly Obese Patients Undergoing Roux‐en‐Y Gastric Bypass

Adiponectin, a peptide hormone, promotes anti‐inflammatory and anti‐atherogenic pathways in the human body, and enhances insulin sensitivity. Hypoadiponectinemia is associated with obesity and other metabolic disorders. The degree of adiponectin dysregulation in patients with obesity appears to be linked to NAFLD (non‐alcoholic fatty liver disease) the hepatic manifestation of the metabolic syndrome. In NAFLD hyperinsulinemia could be a consequence of hypoadiponectinemia. Consequently, it is necessary to determine the level and source of hepatic adiponectin expression. This research is part of the IRB approved clinical trial GHS # 1207–27. Observations and analysis will be conducted on fifty morbidly obese patients that are undergoing Roux‐en‐Y gastric bypass. Immunohistochemistry using a specific anti‐adiponectin antibody shows distribution of adiponectin in liver and omental fat tissue. Adiponectin transcript abundance is assayed using qPCR following the MIQE guidelines. Additionally, circulating levels of total adiponectin are assayed at baseline and 12 weeks post‐surgery. An attempt to use the body‐on‐a‐chip (BOAC) to mimic modulations in adiponectin expression is underway. The BOAC combines computer models of the human body (physiologically based‐pharmacokinetic‐pharmacodinamic PBPK‐PD model) with microfabricated models based on the PBPK and living cells in each compartment. This research is funded by a pilot outreach grant from the Center on Microenvironment and Metastasis (CMM) at Cornell University and a physician's grant from the Guthrie Foundation Investigator‐Initiated Research Grant.

Efeito de dietas hiperlipídicas com extrato de baru e chocolate sobre a área de adipócitos de ratos submetidos ao exercício físico

INTRODUÇÃO: O acúmulo de tecido adiposo provoca uma série de distúrbios metabólicos, os quais poderiam ser atenuados pela modulação dietética e prática de exercícios físicos. OBJETIVO: Avaliar os efeitos de dietas hipercalóricas/hiperlipídicas com extrato de baru e chocolate associadas ao exercício aeróbio sobre a área de adipócitos e triglicérides hepáticos (TGLhep) de ratos. MÉTODOS: Após o desmame, ratos da linhagem Wistar, com exceção dos controles (dieta Nuvilab®; 3,48kcal/g), foram alimentados com dieta à base de chocolate (4,17kcal/g), por dois meses, para indução da obesidade. Feito isso, os animais foram distribuídos em seis grupos: controle sedentários (CS), controle exercitados (CE), baru sedentários (BS), baru exercitados (BE), chocolate sedentários (CHOS), chocolate exercitados (CHOE), de acordo com a introdução da dieta com extrato de baru e treinamento de natação (2% do peso corporal., 8 sem., 5x/semana, 1h/sessão). Após a morte dos animais, o conteúdo de TGLhep foi determinado e os tecidos adiposos retroperitoneal, inguinal e omental foram removidos, pesados e submetidos à avaliação da área de adipócitos. RESULTADOS: As dietas hipercalóricas aumentaram o peso e a área de células do tecido retroperitoneal em relação à dieta controle (p &lt; 0,05). O exercício reduziu a área de células do tecido omental (CHOE: 6.370,91 ± 7.776,13 &lt; CHOS: 7.341,28 ± 5.862,24µm²) e inguinal (CHOE: 5.147,49 ± 5.712,71 &lt; CHOS: 7.083,11 ± 7.682,40µm²) do grupo chocolate e inguinal do controle (CE: 2.212,87 ± 1.920,34 &lt; CS: 3.386,11 ± 3.973,09µm²). O conteúdo de TGLhep dos animais sedentários apresentou-se mais elevado em relação aos animais exercitados e alimentados com as dietas hipercalóricas (BS: 1,36 ± 0,50 &gt; BE: 0,88 ± 0,43mg.100mg-1; CHOS: 1,77 ± 0,64 &gt; CHOE: 0,86 ± 0,41mg.100mg-1). CONCLUSÃO: O treinamento físico em intensidade leve à moderada reduziu significativamente os depósitos adiposos omental (visceral) e inguinal dos animais alimentados com dieta controle e chocolate. Esse mesmo comportamento não foi reproduzido com a dieta à base de extrato de baru. Os animais exercitados apresentaram menor conteúdo de TGLhep, mesmo na persistência das dietas hiperlipídicas/hipercalóricas.

Human Dedifferentiated Adipocytes Show Similar Properties to Bone Marrow‐Derived Mesenchymal Stem Cells

Mature adipocytes are generally considered terminally differentiated because they have lost their proliferative abilities. Here, we studied the gene expression and functional properties of mature adipocytes isolated from human omental and subcutaneous fat tissues. We also focused on dedifferentiated adipocytes in culture and their morphologies and functional changes with respect to mature adipocytes, stromal-vascular fraction (SVF)-derived mesenchymal stem cells (MSCs) and bone marrow (BM)-derived MSCs. Isolated mature adipocytes expressed stem cell and reprogramming genes. They replicated in culture after assuming a fibroblast-like shape and expanded similarly to SVF- and BM-derived MSCs. During the dedifferentiation process, mature adipocytes lost their lineage gene expression profile, assumed the typical mesenchymal morphology and immunophenotype, expressed stem cell genes and differentiated into multilineage cells. Moreover, during the dedifferentiation process, we showed changes in the epigenetic status of mature adipocytes, which led dedifferentiated adipocytes to display a similar DNA methylation condition to BM-derived MSCs. Like SVF- and BM-derived MSCs, dedifferentiated adipocytes were able to inhibit the proliferation of stimulated lymphocytes in coculture while mature adipocytes stimulated their growth. Furthermore, dedifferentiated adipocytes maintained the survival and complete differentiation characteristic of hematopoietic stem cells. This is the first study that in addition to characterizing isolated and dedifferentiated adipocytes also reports on the immunoregulatory and hematopoietic supporting functions of these cells. This structural and functional characterization might have clinical applications of both mature and dedifferentiated adipocytes in such fields, as regenerative medicine.

Adipose tissue-derived PAI-1: A molecular link for thrombo-inflammatory disease states?

Adipose tissue (particularly the visceral adipose tissue of the omentum) was long thought to be a passive, fat-storing cell clump; however, many years ago this view became out-dated. Numerous studies made us aware of the actual character of this contour-determining part of our body: Adipose tissue is considered to be a true organ capable of producing multiple types of hormones, proand anti-inflammatory mediators such as adipokines and other components that are relevant for metabolic control and vascular homeostasis. No wonder that fat tissue-derived factors are dynamically involved in obesity-associated diseases, play an important part in insulin resistance or metabolic syndrome, and are relevant control elements of the cardiovascular system (1). Adipokines constitute a heterogenous group of macromolecules and are divided into those produced by fat cells (such as leptin or adiponectin) and those released by non-fat cells, including several interleukins, tumour necrosis factor (TNF)-α as well as plasminogen activator inhibitor-1 (PAI-1) (2, 3). Moreover, the repertoire of adipokines, particularly when released under stimulatory/inflammatory conditions, may differ considerably between omental and subcutaneous fat tissue. Thus, adipose tissuederived factors may act in a paracrine fashion at the interface with other organs or tissues, as was proposed for the fat–bone relationship (4). Against this background, in this issue of Thrombosis and Haemostasis, Ekstrom et al. (5) provide experimental evidence in humans for a potential cross-talk between an acute inflammatory situation (such as open heart surgery in a small group of patients) and fat. This situation lead to a significant stimulation of PAI-1 gene expression in omental adipose tissue, accompanied by increased plasma levels of PAI-1 antigen over several hours during the post-operative period (5). Consequently, the authors propose that such inflammation-provoked elevated PAI-1 levels would diminish the t-PAmediated fibrinolytic potential in these patients, resulting in an increased risk of myocardial infarction. As the origin of chronically elevated PAI-1 levels in situations of spontaneous arterial thrombosis or early vein graft rejection is largely unknown, this first study in human subjects offers a promising approach to define mechanistic relations between adipose tissue and other disturbed organs with regard to the thrombo-inflammatory axis. Yet, one should be careful to over-interpret these findings (as already indicated by the authors), since several aspects may limit the conclusions of this small study. Further experimental work is required to clarify the following issues: (a) Although the elevation in PAI-1 antigen may also imply increased PAI-1 activity and enhanced inhibition of t-PA (with an increase in t-PA-PAI-1 complexes), these parameters were not determined, indicating that an impact on fibrinolysis may be assumed but was not experimentally demonstrated; (b) in addition to omental tissue being a major origin of the protease inhibitor, elevated plasma PAI-1 levels could be derived from activated platelets as well, which would fit with the known inflammatory role of platelets in different vascular diseases (6); (c) although quantitatively less pronounced when compared to omental fat tissue, epicardial adipose tissue may very well be responsive to acute inflammatory situations during open heart surgery, particularly due to its close proximity to the organ under operation. Here, further analysis to clarify mechanisms of a paracrine crosstalk provoked by adipokines may be worth considering. And finally, (d) the authors did not mention any PAI-1 targeting approaches that may add to an anti-inflammatory regimen with antagonists towards interleukins or TNF-α; here, PAI-1 inhibitors may very well be suitable to limit the risk of vascular diseases, including myocardial infarction, in the post-operative period and beyond (7). Together with their first study in human patients the authors provide some clues for a thrombo-inflammatory connection between open heart surgery and increased PAI-1 production in adipose tissue. These initial findings may stimulate further translational investigations as to the potential role of adipokines and their direct or indirect contribution in thrombosis and haemostasis.