scholarly journals Adenovirus 36 DNA in Adipose Tissue of Patient with Unusual Visceral Obesity

2010 ◽  
Vol 16 (5) ◽  
pp. 850-852 ◽  
Author(s):  
Behrouz Salehian ◽  
Stephen J. Forman ◽  
Fouad R. Kandeel ◽  
Denise E. Bruner ◽  
Jia He ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Obesity ◽  
Adenovirus 36

scholarly journals Adenovirus 36 DNA in human adipose tissue

2015 ◽  
Vol 39 (12) ◽  
pp. 1761-1764 ◽  
Author(s):  
E Ponterio ◽  
R Cangemi ◽  
S Mariani ◽  
G Casella ◽  
A De Cesare ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Adenovirus 36

scholarly journals Lack of adipose-specific hexose-6-phosphate dehydrogenase causes inactivation of adipose glucocorticoids and improves metabolic phenotype in mice

2019 ◽  
Vol 133 (21) ◽  
pp. 2189-2202
Author(s):  
Jian Wang ◽  
Ying Wang ◽  
Limei Liu ◽  
Kabirullah Lutfy ◽  
Theodore C. Friedman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fasting Blood Glucose ◽  
Visceral Obesity ◽  
Conditional Knockout ◽  
Hormone Sensitive Lipase ◽  
Metabolic Phenotype ◽  
Mrna Levels ◽  
Obesity And Diabetes ◽  
Factor C

Abstract Excessive glucocorticoid (GC) production in adipose tissue promotes the development of visceral obesity and metabolic syndrome (MS). 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is critical for controlling intracellular GC production, and this process is tightly regulated by hexose-6-phosphate dehydrogenase (H6PDH). To better understand the integrated molecular physiological effects of adipose H6PDH, we created a tissue-specific knockout of the H6PDH gene mouse model in adipocytes (adipocyte-specific conditional knockout of H6PDH (H6PDHAcKO) mice). H6PDHAcKO mice exhibited almost complete absence of H6PDH expression and decreased intra-adipose corticosterone production with a reduction in 11β-HSD1 activity in adipose tissue. These mice also had decreased abdominal fat mass, which was paralleled by decreased adipose lipogenic acetyl-CoA carboxylase (ACC) and ATP-citrate lyase (ACL) gene expression and reduction in their transcription factor C/EBPα mRNA levels. Moreover, H6PDHAcKO mice also had reduced fasting blood glucose levels, increased glucose tolerance, and increased insulin sensitivity. In addition, plasma free fatty acid (FFA) levels were decreased with a concomitant decrease in the expression of lipase adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in adipose tissue. These results indicate that inactivation of adipocyte H6PDH expression is sufficient to cause intra-adipose GC inactivation that leads to a favorable pattern of metabolic phenotypes. These data suggest that H6PDHAcKO mice may provide a good model for studying the potential contributions of fat-specific H6PDH inhibition to improve the metabolic phenotype in vivo. Our study suggests that suppression or inactivation of H6PDH expression in adipocytes could be an effective intervention for treating obesity and diabetes.

scholarly journals Elevated serum uric acid is a facilitating mechanism for insulin resistance mediated accumulation of visceral adipose tissue

2020 ◽  
Author(s):  
Luisa Fernández-Chirino ◽  
Neftali Eduardo Antonio-Villa ◽  
Arsenio Vargas-Vázquez ◽  
Paloma Almeda-Valdés ◽  
Donají Gómez-Velasco ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Visceral Adipose Tissue ◽  
Visceral Obesity ◽  
Causal Mechanism ◽  
Mediation Analyses ◽  
Bidirectional Relationship ◽  
Visceral Adipose

BACKGROUND: Serum uric acid (SUA) has a relationship with cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation. Here, we aimed to clarify the nature of this relationship and the underlying causality mechanism. METHODS: We conducted a population-based cross-sectional study comprising 8,504 subjects joining both NHANES 2003-2004 and 2011-2012 cycles and ENSANUT Medio Camino 2016. We performed mixed effects linear regression models using HOMA2-IR, adipoIR, and METS-VF as indicators of IR and VAT accumulation. Furthermore, we performed mediation analyses to assess a potential causal mechanism and ROC curves to establish cut-off points for identification of IR and visceral obesity using SUA. Finally, with an additional dataset comprised of 226 subjects with both euglycemic hyperinsulinemic clamp (EHC) and dual X-ray absorptiometry (DXA) measurements for IR and VAT accumulation, we performed a network of confirmatory mediation analyses. RESULTS:We found that SUA has a mediating role inside the bidirectional relationship between IR and visceral obesity, and it is part of an underlying causality mechanism which includes adiponectin. The proportion of the mechanism mediated by SUA is greater when stated that IR (in either peripheral or adipose tissue) leads to VAT accumulation (14.90%[13.20%-17.00%] and 15.54%[13.61% - 18.00%] to 4.88%[3.06%-7.00%] and 8.13%[5.91% - 10.00%]) instead of the opposite direction. This result was confirmed by mediation analyses using gold-standard measurements. CONCLUSIONS:Elevated SUA acts as mediator inside the bidirectional relationship between IR andVAT accumulation. Its role appears to be larger when considering adipose tissue IR as the promoter for VAT accumulation.

scholarly journals Genetic and Pharmacological Inhibition of PAPP-A Protects Against Visceral Obesity in Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (10) ◽  
Author(s):  
Akhila Ramakrishna ◽  
Laurie K Bale ◽  
Sally A West ◽  
Cheryl A Conover
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Liver Lipid ◽  
Protein A ◽  
Visceral Obesity ◽  
Cell Number ◽  
Metabolic Effects ◽  
Adipocyte Size ◽  
Fat Depots ◽  
Mesenteric Fat

Abstract Pathogenicity of visceral adipose tissue (VAT) has been linked to the metabolic stress of enlarging mature adipocytes and a limited ability to recruit new adipocytes. One of the major distinguishing features of VAT preadipocytes is the high expression of the zinc metalloprotease, pregnancy-associated plasma protein-A (PAPP-A), when compared to subcutaneous adipose tissue (SAT). In this study we used 2 different approaches to investigate the effect of PAPP-A inhibition on different fat depots in mice on a high-fat diet (HFD) for 15 weeks. Conditional knockdown of PAPP-A gene expression in female adult mice resulted in significant decreases of 30% to 40% in adipocyte size in VAT (mesenteric and pericardial depots) compared to control mice. There was no effect on SAT (inguinal) or intra-abdominal perigonadal fat. Liver lipid was also significantly decreased without any effect on heart and skeletal muscle lipid. We found similar effects when using a pharmacological approach. Weekly injections of a specific immunoneutralizing monoclonal antibody (mAb-PA 1/41) or isotype control were given to male and female wild-type mice on HFD for 15 weeks. Adipocyte size was significantly decreased (30%-50%) only in VAT with mAb-PA 1/41 treatment. In this model, cell number was significantly increased in mesenteric fat in mice treated with mAb-PA 1/41, suggesting hyperplasia along with reduced hypertrophy in this VAT depot. Gene expression data indicated a significant decrease in F4/80 (macrophage marker) and interleukin-6 (proinflammatory cytokine) and a significant increase in adiponectin (anti-inflammatory adipokine with beneficial metabolic effects) in mesenteric fat compared to inguinal fat in mice treated with mAb-PA 1/41. Furthermore, there was significantly decreased liver lipid content with mAb-PA 1/41 treatment. Thus, using 2 different models systems we provide proof of principle that PAPP-A inhibition is a potential therapeutic target to prevent visceral obesity and its metabolic sequelae, such as fatty liver.

scholarly journals Iron Deficiency Anemia (IDA) Promotes Visceral Obesity Due to Defective Adipose Tissue Browning (OR09-07-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jin-Seon Yook ◽  
Mi Zhou ◽  
Lee Jaekwon ◽  
Soonkyu Chung
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Iron Deficiency ◽  
Heat Release ◽  
Iron Deficiency Anemia ◽  
Mitochondrial Biogenesis ◽  
Iron Content ◽  
Visceral Obesity ◽  
Deficiency Anemia ◽  
Tissue Browning

Abstract Objectives Iron deficiency anemia (IDA) is a common disease related to malnutrition. Epidemiological studies revealed a positive correlation between IDA and obesity, but the underlying mechanism is uncertain. Emerging evidence suggests that adipose browning significantly contributes to weight loss by dissipating extra energy into heat. Adipose tissue browning is concurrent with mitochondrial biogenesis, an iron-demanding process. We aimed to investigate whether iron deficiency downregulat adipose tissue browning. Methods To simulate the IDA, C57BL/6 mice were fed a high-fat diet in an iron-deficient (3 ppm) setting for 14 weeks compared with an isocaloric iron-sufficient (50 ppm) diet. Iron status was evaluated by measuring serum levels of ferritin, hemoglobin (Hb) and hematocrit (HCt). Iron content of tissue levels was measured by ICP-Mass spectrometer. For assessment of capability to keep the temperature homeostasis, core body temperature and heat release by the infrared camera were determined upon acute cold exposure (4°C). Adipose browning was induced by administrating β3-adrenoceptor agonist, CL316243 (CL) for 5 days. The significance of iron on adipocyte browning was validated in vitro by silencing of the transferrin receptor (TfR), or by iron chelator (DFO, deferoxamine) treatment during beige adipogenesis. Results The chronic iron-deficiency significantly reduced serum ferritin concentration (P < 0.01) with marginal impact on Hb or HCt. Despite no apparent difference in body weight, fat mass was higher in IDA mice (P < 0.001). Consistently, total iron content in the inguinal fat, where adipose browning occurs, was markedly lower in IDA mice. IDA mice were more susceptible to cold treatment, maintaining the body temperature lower than control and defective in heat release. Upon CL stimulation, IDA mice showed reduced expression of uncoupling protein 1 (UCP1) and Cytc, and beige-like morphology in the inguinal fat. Supporting these in vivo results, inhibition of iron import by depleting TfR or reducing liable iron dampened the beige adipogenesis by attenuating brown-specific markers and mitochondrial biogenesis. Conclusions IDA is an independent risk factor for visceral obesity by decreasing thermogenic energy expenditure. Funding Sources National Institutes of Health Grant 1R21HD094273.

scholarly journals Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance

2016 ◽  
Vol 2 (3) ◽  
pp. e1501332 ◽  
Author(s):  
Sachiko Nishimoto ◽  
Daiju Fukuda ◽  
Yasutomi Higashikuni ◽  
Kimie Tanaka ◽  
Yoichiro Hirata ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Visceral Obesity ◽  
Sterile Inflammation ◽  
Model Assessment ◽  
Wild Type ◽  
Exogenous Dna ◽  
Monocyte Chemoattractant Protein 1 ◽  
Macrophage Accumulation

Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9−/−) macrophages. Fat-fed Tlr9−/− mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9−/− mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography–determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.

Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action

2006 ◽  
Vol 290 (6) ◽  
pp. E1253-E1261 ◽  
Author(s):  
Rong-Ze Yang ◽  
Mi-Jeong Lee ◽  
Hong Hu ◽  
Jessica Pray ◽  
Hai-Bin Wu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cdna Library ◽  
Insulin Action ◽  
Signal Sequence ◽  
Visceral Obesity ◽  
Northern Analysis ◽  
Protein Sequence Analysis ◽  
Omental Adipose Tissue ◽  
Fat Depots

Central (visceral) obesity is more closely associated with insulin resistance, type 2 diabetes, and cardiovascular disease than is peripheral [subcutaneous (sc)] obesity, but the underlying mechanism for this pathophysiological difference is largely unknown. To understand the molecular basis of this difference, we sequenced 10,437 expressed sequence tags (ESTs) from a human omental fat cDNA library and discovered a novel visceral fat depot-specific secretory protein, which we have named omentin. Omentin ESTs were more abundant than many known adipose genes, such as perilipin, adiponectin, and leptin in the cDNA library. Protein sequence analysis indicated that omentin mRNA encodes a peptide of 313 amino acids, containing a secretory signal sequence and a fibrinogen-related domain. Northern analysis demonstrated that omentin mRNA was predominantly expressed in visceral adipose tissue and was barely detectable in sc fat depots in humans and rhesus monkeys. Quantative real-time PCR showed that omentin mRNA was expressed in stromal vascular cells, but not fat cells, isolated from omental adipose tissue, with >150-fold less in sc cell fractions. Accordingly, omentin protein was secreted into the culture medium of omental, but not sc, fat explants. Omentin was detectable in human serum by Western blot analysis. Addition of recombinant omentin in vitro did not affect basal but enhanced insulin-stimulated glucose uptake in both sc (47%, n = 9, P = 0.003) and omental (∼30%, n = 3, P < 0.05) human adipocytes. Omentin increased Akt phosphorylation in the absence and presence of insulin. In conclusion, omentin is a new adipokine that is expressed in omental adipose tissue in humans and may regulate insulin action.

scholarly journals Transgenic overexpression of hexose-6-phosphate dehydrogenase in adipose tissue causes local glucocorticoid amplification and lipolysis in male mice

2014 ◽  
Vol 306 (5) ◽  
pp. E543-E551 ◽  
Author(s):  
Ying Wang ◽  
Limei Liu ◽  
Hanze Du ◽  
Yoshiko Nagaoka ◽  
Winnie Fan ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Visceral Obesity ◽  
Abdominal Fat ◽  
Fatty Acid Binding ◽  
Metabolic Phenotypes ◽  
Lipolytic Action ◽  
Glucocorticoid Production

The prereceptor activation of glucocorticoid production in adipose tissue by NADPH-dependent 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has emerged as a potential mechanism in the pathogenesis of visceral obesity and metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) is an endoplasmic reticulum lumen-resident enzyme that generates cofactor NADPH and thus mediates 11β-HSD1 activity. To determine the role of adipose H6PDH in the prereceptor modulation of 11β-HSD1 and metabolic phenotypes, we generated a transgenic (Tg) mouse model overexpressing H6PDH under the control of the enhancer-promoter region of the adipocyte fatty acid-binding protein (aP2) gene (aP2/H6PDH Tg mice). Transgenic aP2/H6PDH mice exhibited relatively high expression of H6PDH and elevated corticosterone production with induction of 11β-HSD1 activity in adipose tissue. This increase in corticosterone production in aP2-H6PDH Tg mice resulted in mild abdominal fat accumulation with induction of C/EBP mRNA expression and slight weight gain. Transgenic aP2/H6PDH mice also exhibited fasting hyperglycemia and glucose intolerance with insulin resistance. In addition, the aP2/H6PDH Tg mice have elevated circulating free fatty acid levels with a concomitant increased adipose lipolytic action associated with elevated HSL mRNA and Ser660 HSL phosphorylation within abdominal fat. These results suggest that increased H6PDH expression specifically in adipose tissue is sufficient to cause intra-adipose glucocorticoid production and adverse metabolic phenotypes. These findings suggest that the aP2/H6PDH Tg mice may provide a favorable model for studying the potential impact of H6PDH in the pathogenesis of human metabolic syndrome.

scholarly journals Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Akinobu Maeda ◽  
Kouichi Tamura ◽  
Hiromichi Wakui ◽  
Masato Ohsawa ◽  
Kengo Azushima ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Visceral Obesity ◽  
Pleiotropic Effects ◽  
Stress Axis ◽  
Therapeutic Effects ◽  
Kkay Mice ◽  
Adipocyte Hypertrophy

In the present study, we examined the therapeutic effects of olmesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders with visceral obesity, with a focus on an olmesartan effect on the adipose tissue. Olmesartan treatment (3 mg/kg per day) for 4 weeks significantly lowered systolic blood pressure but did not affect body weight during the study period in KKAy mice. However, there were three interesting findings possibly related to the pleiotropic effects of olmesartan on adipose tissue in KKAy mice: (1) an inhibitory effect on adipocyte hypertrophy, (2) a suppressive effect on IL-6 gene expression, and (3) an ameliorating effect on oxidative stress. On the other hand, olmesartan exerted no evident influence on the adipose tissue expression of AT1R-associated protein (ATRAP), which is a molecule interacting with AT1R so as to inhibit pathological AT1R activation and is suggested to be an emerging molecular target in metabolic disorders with visceral obesity. Collectively, these results suggest that the blood pressure lowering effect of olmesartan in KKAy mice is associated with an improvement in adipocyte, including suppression of adipocyte hypertrophy and inhibition of the adipose IL-6-oxidative stress axis. Further study is needed to clarify the functional role of adipose ATRAP in the pleiotropic effects of olmesartan.

scholarly journals Adipokine-cytokine profile of adipocytes of epicardial adipose tissue in ischemic heart disease complicated by visceral obesity

2017 ◽  
Vol 14 (4) ◽  
pp. 38-45 ◽  
Author(s):  
Olga V. Gruzdeva ◽  
Daria A. Borodkina ◽  
Olga E. Akbasheva ◽  
Julia A. Dileva ◽  
Larisa V. Antonova ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Blood Serum ◽  
Epicardial Adipose Tissue ◽  
Visceral Obesity ◽  
Cytokine Profile ◽  
Ischemic Heart ◽  
Atherogenic Dyslipidemia ◽  
Soluble Receptor

Introduction. To date, cardiovascular diseases (CVD) remain the main cause of disability and mortality in population. The majority of ectopic fat deposits demonstrated a reliable association with cardiometabolic risks and clinical manifestations of most CVD. The elucidation of the metabolic features of adipocytes of epicardial adipose tissue localized in the immediate vicinity of the lesion in ischemic heart disease (IHD) can have both theoretical and practical significance for pathophysiology and cardiology. Aim. To study the adipokine-cytokine profile of epicardial adipocytes (EA) and subcutaneous adipose tissue (SCAT), blood serum in relation to the area of visceral adipose tissue (AVAT), biochemical and rhelinic characteristics of IHD patients. Methods. 84 patients (70 men and 14 women) with IHD were examined. In the presence of visceral obesity (VO), patients were divided into two groups. In patients with VO, adipocyte EA and SCAT were sampled, followed by cultivation and evaluation of adipokine and proinflammatory activity. The parameters of carbohydrate and lipid metabolism, adipokine and proinflammatory status in blood serum were determined. Results. It has been established that the adipokine-cytokine profile of the adipocytes EA and SCAT differ. Adipocytes of EA in IHD on the background of VO are characterized by an increase in IL-1, TNF-, leptin-adiponectin ratio and a decrease in the protective factors: adiponectin and anti-inflammatory cytokine IL-10. While adipocytes of SCAT were characterized by a decrease in the concentration of the soluble receptor to leptin and a more pronounced leptin resistance, and the increase in inflammatory cytokines was compensated by an increase in the concentration of IL-10, the presence of VO was associated with multivessel coronary disease, multifocal atherosclerosis, insulin resistance, atherogenic dyslipidemia, adipokine imbalance, and markers of inflammation. Thus, the value of the area of VO determined higher values of leptin concentration, TNF- in adipocytes and serum, lipid and carbohydrate metabolism and a lower soluble receptor for leptin content. The conclusion. Thus, in IHD with VO the state of adipocytes, EA is characterized as "metabolic inflammation" and may indicate the direct involvement of adipocytes in the pathogenesis of IHD due to the formation of adipokine imbalance and the activation of proinflammatory reactions.

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