Dataset Information

The Role of Olfactomedin 2 in the Adipose Tissue-Liver Axis and Its Implication in Obesity-Associated Nonalcoholic Fatty Liver Disease.

ABSTRACT: This study's objective was to assess the involvement of olfactomedin 2 (OLFM2), a secreted glycoprotein related to lipid metabolism regulation, in nonalcoholic fatty liver disease (NAFLD) mediated by the adipose-tissue-liver axis. OLFM2 mRNA expression was analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue by RT-qPCR. The cohort included women with normal weight (n = 16) or morbid obesity (MO, n = 60) who were subclassified into normal liver (n = 20), simple steatosis (n = 21), and nonalcoholic steatohepatitis (NASH, n = 19) groups. The results showed that OLFM2 expression in SAT was enhanced in MO individuals and in the presence of NAFLD. Specifically, OLFM2 expression in SAT was increased in mild and moderate degrees of steatosis in comparison to the absence of it. Moreover, OLFM2 expression in SAT was negatively correlated with interleukin-6 levels. On the other hand, OLFM2 expression in VAT decreased in the presence of NASH and exhibited a positive correlation with adiponectin levels. In conclusion, OLFM2 in SAT seems to be implicated in hepatic lipid accumulation. Additionally, since we previously suggested the possible implication of hepatic OLFM2 in NAFLD progression, now we propose a possible interaction between the liver and SAT, reinforcing the potential implication of this tissue in NAFLD development.

SUBMITTER: Barrientos-Riosalido A

PROVIDER: S-EPMC10049551 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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The Role of Olfactomedin 2 in the Adipose Tissue-Liver Axis and Its Implication in Obesity-Associated Nonalcoholic Fatty Liver Disease.

Barrientos-Riosalido Andrea A Bertran Laia L Vilaró-Blay Mercè M Aguilar Carmen C Martínez Salomé S Paris Marta M Sabench Fàtima F Riesco David D Binetti Jessica J Castillo Daniel Del DD Richart Cristóbal C Auguet Teresa T

International journal of molecular sciences 20230309 6

This study's objective was to assess the involvement of olfactomedin 2 (OLFM2), a secreted glycoprotein related to lipid metabolism regulation, in nonalcoholic fatty liver disease (NAFLD) mediated by the adipose-tissue-liver axis. OLFM2 mRNA expression was analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue by RT-qPCR. The cohort included women with normal weight (n = 16) or morbid obesity (MO, n = 60) who were subclassified into normal liver (n = 20), simple steatosis (n = 21), and ...[more]

PMID: 36982296

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Project description:Background and aimsInsulin resistance is a key factor in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We evaluated the importance of subcutaneous abdominal adipose tissue (SAAT) inflammation and both plasma and SAAT-derived exosomes in regulating insulin sensitivity in people with obesity and NAFLD.MethodsAdipose tissue inflammation (macrophage and T-cell content and expression of proinflammatory cytokines), liver and whole-body insulin sensitivity (assessed using a hyperinsulinemic-euglycemic clamp and glucose tracer infusion), and 24-hour serial plasma cytokine concentrations were evaluated in 3 groups stratified by adiposity and intrahepatic triglyceride (IHTG) content: (1) lean with normal IHTG content (LEAN; N = 14); (2) obese with normal IHTG content (OB-NL; N = 28); and (3) obese with NAFLD (OB-NAFLD; N = 28). The effect of plasma and SAAT-derived exosomes on insulin-stimulated Akt phosphorylation in human skeletal muscle myotubes and mouse primary hepatocytes was assessed in a subset of participants.ResultsProinflammatory macrophages, proinflammatory CD4 and CD8 T-cell populations, and gene expression of several cytokines in SAAT were greater in the OB-NAFLD than the OB-NL and LEAN groups. However, with the exception of PAI-1, which was greater in the OB-NAFLD than the LEAN and OB-NL groups, 24-hour plasma cytokine concentration areas-under-the-curve were not different between groups. The percentage of proinflammatory macrophages and plasma PAI-1 concentration areas-under-the-curve were inversely correlated with both hepatic and whole-body insulin sensitivity. Compared with exosomes from OB-NL participants, plasma and SAAT-derived exosomes from the OB-NAFLD group decreased insulin signaling in myotubes and hepatocytes.ConclusionsSystemic insulin resistance in people with obesity and NAFLD is associated with increased plasma PAI-1 concentrations and both plasma and SAAT-derived exosomes. ClinicalTrials.gov number: NCT02706262 (https://clinicaltrials.gov/ct2/show/NCT02706262).

Project description:Background and aimsEpicardial adipose tissue (EAT) has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD). Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1) the association between EAT, the other metabolic parameters and the severity of steatosis 2) the relationship between cardiovascular (cIMT, cplaques, E/A), liver (presence of NASH and significant fibrosis) damage and metabolic risk factors including EAT 3) the relationship between EAT and genetic factors strongly influencing liver steatosis.MethodsIn a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100). EAT, severity of steatosis, carotid intima-media thickness (cIMT) and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm) were female gender (p = 0.003), age (p = 0.001), BMI (p = 0.01), diastolic blood pressure (p = 0.009), steatosis grade 2 (p = 0.01) and 3 (p = 0.04), fatty liver index (p = 0.001) and statin use (p = 0.03). Variables independently associated with carotid IMT were age (p = 0.0001), hypertension (p = 0.009), diabetes (p = 0.04), smoking habits (p = 0.04) and fatty liver index (p = 0.02), with carotid plaques age (p = 0.0001), BMI (p = 0.03), EAT (p = 0.02),) and hypertension (p = 0.02), and with E/A age (p = 0.0001), diabetes (p = 0.005), hypertension (p = 0.04) and fatty liver index (p = 0.004). In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH) was independently associated with EAT (p = 0.04) and diabetes (p = 0.054) while significant fibrosis with EAT (p = 0.02), diabetes (p = 0.01) and waist circumference (p = 0.05). No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found.ConclusionIn patients with NAFLD, EAT is associated with the severity of liver and vascular damage besides with the known metabolic risk factors.

Dataset Information

The Role of Olfactomedin 2 in the Adipose Tissue-Liver Axis and Its Implication in Obesity-Associated Nonalcoholic Fatty Liver Disease.

Publications

The Role of Olfactomedin 2 in the Adipose Tissue-Liver Axis and Its Implication in Obesity-Associated Nonalcoholic Fatty Liver Disease.

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