Adipose Tissue Distribution and Quantification of PPARβ/δ and PPARγ1-3 mRNAs: Discordant Gene Expression in Subcutaneous, Retroperitoneal and Visceral Adipose Tissue of Morbidly Obese Patients

Objective Obesity is a negative prognostic factor for various clinical conditions. In this observational cohort study, we evaluated a CT-based assessment of the adipose tissue distribution as a potential non-invasive prognostic parameter in critical illness. Methods Routine CT-scans upon admission to the intensive care unit (ICU) were used to analyze the visceral and subcutaneous adipose tissue areas at the 3rd lumbar vertebra in 155 patients. Results were correlated with various prognostic markers and both short-term- and overall survival. Multiple statistical tools were used for data analysis. Results We observed a significantly larger visceral adipose tissue area in septic patients compared to non-sepsis patients. Interestingly, patients requiring mechanical ventilation had a significantly higher amount of visceral adipose tissue correlating with the duration of mechanical ventilation. Moreover, both visceral and subcutaneous adipose tissue area significantly correlated with several laboratory markers. While neither the visceral nor the subcutaneous adipose tissue area was predictive for short-term ICU survival, patients with a visceral adipose tissue area above the optimal cut-off (241.4 cm2) had a significantly impaired overall survival compared to patients with a lower visceral adipose tissue area. Conclusions Our study supports a prognostic role of the individual adipose tissue distribution in critically ill patients. However, additional investigations need to confirm our suggestion that routine CT-based assessment of adipose tissue distribution can be used to yield further information on the patients’ clinical course. Moreover, future studies should address functional and metabolic analysis of different adipose tissue compartments in critical illness.

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Effect of surgically induced weight loss on serum adiponectin levels and its association with the gene expression in visceral adipose tissue of morbidly obese individuals

Clinica Chimica Acta ◽

10.1016/j.cca.2019.03.631 ◽

2019 ◽

Vol 493 ◽

pp. S306

Author(s):

R. Yadav ◽

S. Aggarwal ◽

A. Singh ◽

R. Mir

Keyword(s):

Gene Expression ◽

Weight Loss ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Serum Adiponectin ◽

Morbidly Obese ◽

Visceral Adipose ◽

Surgically Induced

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Overexpression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Hepatic and Visceral Adipose Tissue is Associated with Metabolic Disorders in Morbidly Obese Patients

Obesity Surgery ◽

10.1007/s11695-009-9937-0 ◽

2009 ◽

Vol 20 (1) ◽

pp. 77-83 ◽

Cited By ~ 38

Author(s):

René Baudrand ◽

Cristian A. Carvajal ◽

Arnoldo Riquelme ◽

Mauricio Morales ◽

Nancy Solis ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Metabolic Disorders ◽

Hydroxysteroid Dehydrogenase ◽

Morbidly Obese ◽

Obese Patients ◽

Visceral Adipose

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LMO3 reprograms visceral adipocyte metabolism during obesity

Journal of Molecular Medicine ◽

10.1007/s00109-021-02089-9 ◽

2021 ◽

Author(s):

Gabriel Wagner ◽

Anna Fenzl ◽

Josefine Lindroos-Christensen ◽

Elisa Einwallner ◽

Julia Husa ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Glucose Uptake ◽

Visceral Adipose Tissue ◽

Tissue Expansion ◽

Oxidative Capacity ◽

Glut4 Translocation ◽

Mitochondrial Oxidative Capacity ◽

Visceral Adipose

Abstract Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high-fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics, as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain or loss of LMO3 expression, respectively. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. LMO3 expression in eWAT significantly improved insulin sensitivity and healthy visceral adipose tissue expansion in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, LMO3 expression in 3T3-L1 adipocytes increased PPARγ transcriptional activity, insulin-stimulated GLUT4 translocation and glucose uptake, as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. Mechanistically, LMO3 induced the PPARγ coregulator Ncoa1, which was required for LMO3 to enhance glucose uptake and mitochondrial oxidative gene expression. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose metabolism, insulin sensitivity, mitochondrial function, and adiponectin secretion. Together with increased PPARγ activity and Ncoa1 expression, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity. Key messages LMO3 increases beneficial visceral adipose tissue expansion and insulin sensitivity in vivo. LMO3 increases glucose uptake and oxidative mitochondrial activity in adipocytes. LMO3 increases nuclear coactivator 1 (Ncoa1). LMO3-enhanced glucose uptake and mitochondrial gene expression requires Ncoa1.

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A214 BARIATRIC SURGERY PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE HAVE DIFFERENT VISCERAL ADIPOSE TISSUE GENE EXPRESSION COMPARED TO THOSE WITH NORMAL LIVER

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.212 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 245-247

Author(s):

S Keshavjee ◽

J Yadav ◽

K Schwenger ◽

S Fischer ◽

T D Jackson ◽

...

Keyword(s):

Gene Expression ◽

Bariatric Surgery ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Inflammatory Markers ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Visceral Adipose ◽

Healthy Liver ◽

Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis (SS) and nonalcoholic steatohepatitis (NASH). It affects 74–98% of individuals with morbid obesity undergoing bariatric surgery (BSX). Among several factors contributing to NAFLD pathogenesis, adipokines secreted by visceral adipose tissue (VAT) can play a role by regulating glucose/lipid metabolism and inflammation. Aims This study aims to determine if visceral adipose tissue adipokine and cytokine gene expression are associated with NAFLD (SS and NASH) at the time of BSX. Methods Patients were recruited from the Toronto Western Hospital Bariatric Clinic. Demographic data was recorded. The VAT and liver biopsies were collected at the time of bariatric surgery. VAT adipokines and other mediators were assessed by RT-PCR and included markers of thermogenic capacity, inflammation, fibrosis, adipokines, and others. Liver histology was assessed by a pathologist using the Brunt system and individuals were diagnosed as either SS, NASH, or having a healthy liver (HL). Blood samples were collected pre-BSX to measure liver and metabolic syndrome related parameters, including HOMA-IR, HbA1c, liver enzymes, and lipid profile. Anthropometry was also assessed. Groups were compared using Kruskal-Wallis test followed by Wilcoxon ranked sum, or chi-square and Fisher’s exact test as necessary. Data was considered to be statistically significant with a p-value less than 0.05. Results We are presenting data on 126 patients, 80.2% females with a median age of 49 and a body mass index (BMI) of 46.9. Fifty-seven patients had SS, 34 had NASH and 35 had a healthy liver (HL). BMI, age, and sex did not differ between the three groups. First, we found that those with NASH had significantly higher VAT expression of fibrosis (Loxl2), inflammation (CCL4 and TGFb1) and proliferation markers (E2F1) and significantly lower expression of adipokines (TNFa and resistin) compared to HL. Also, we found that SS had significantly higher fibrosis (Col3a1, Col6a1, Loxl2, CD9 and Acta2), inflammation (Nox2, TGFb1, IFNg and Clec10a), browning (PPARa, PPARg and Glut1) and proliferation (E2F1) marker expression compared to HL. Conclusions Results show that there is a significant difference in the expression pattern of VAT fibrotic and inflammatory markers between HL, SS and NASH patients. The observed increase of inflammatory markers in NAFLD is in line with prior research outlining the ability of inflammatory mediators from VAT to contribute to liver pathology via portal circulation. The relationship between VAT characteristics and NAFLD are important in understanding the widespread metabolic effects of obesity. Funding Agencies CIHRCanadian Liver foundation

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