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Published on: April 3, 2017
Obesity-associated Inflammation Induces microRNA-155 Expression in Adipocytes and Adipose Tissue: Outcome on
Esma Karkeni1, Julien Astier1, Franck Tourniaire1
1Institut National de Recherche Agronomique (INRA) (E.K., J.A., F.T., M.E.A., B.R., E.G., P.B., J.-F.L.), UMR 1260, F-13385, Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 1062 (E.K., J.A., F.T., M.E.A., B.R., E.G., P.B., J.F.L.), Nutrition, Obésité et Risque Thrombotique F-13385, Marseille, France; Faculté de Médecine (E.K., J.A., F.T., M.E.A., B.R., E.G., P.B., J.-F.L.), Aix-Marseille Université, F-13385, Marseille, France; Pennington Biomedical Research Center (L.W., J.Y.), Louisiana State University System, Baton Rouge, LA 70808; Laboratory of Transplant Immunology, Regeneration Medicine Research Center, Sichuan University, Sichuan Province, 610041 China; and UMR INRA 1019 Unité de Nutrition Humaine (J.S., S.W.), Centre de Recherches INRA de Clermont-Ferrand/Theix, 63122 St-Genès-Champanelle, France.
Context:
Obesity alters adipose tissue's metabolic and endocrine functions and causes a chronic local and systemic low-grade inflammatory state to develop, generating obesity-associated complications. In the last decade, many entities contributing to and regulating this inflammatory state have been identified, among which are microRNAs.
Objective:
This study aimed to identify microRNA regulated in inflamed adipocytes and adipose tissue, and its effect on adipocyte biology.
Design And Results:
We screened the expression profile of TNFα-treated adipocytes (a major pro-inflammatory protein expressed in obese adipose tissue), and identified miR-155 as the most responsive microRNA. The involvement of TNFα on the basal miR-155 expression was confirmed in the adipose tissue of Tnfa−/− mice where miR-155 was significantly reduced. Also, mice overexpressing p65 or invalidated for p65 in adipose tissue respectively increased and decreased miR-155 expression, in line with the involvement of the nuclear factor κB (NF-κB) pathway in miR-155 induction. miR-155 expression was higher in obese subjects' adipose tissue than in that of normal-weight subjects, and correlated with TNFα expression and body mass index. Gain and loss of function of miR-155 showed its effect on adipocyte function, probably via its ability to target PPARγ mRNA 3′UTR. Interestingly, miR-155 overexpression also resulted in an increased inflammatory state in adipocytes.
Conclusion:
Altogether, these data are evidence of a proinflammatory loop mediated by NF-κB and miR-155 that could participate in the amplification of inflammatory status in adipocytes.
Insights
Obesity promotes inflammation in fat tissue, involving microRNAs (miRNAs). This study identifies miR-155 as a key player, regulated by tumor necrosis factor-alpha (TNFα) and nuclear factor-kappa B (NF-κB), contributing to obesity-associated inflammation.
Area of Science:
- Adipose tissue biology
- Molecular mechanisms of inflammation
- MicroRNA regulation
Background:
- Obesity disrupts adipose tissue function, leading to chronic inflammation and complications.
- MicroRNAs (miRNAs) are increasingly recognized as regulators of inflammatory states.
Purpose of the Study:
- To identify specific microRNAs involved in inflamed adipocytes and adipose tissue.
- To investigate the role of these microRNAs in adipocyte biology and inflammatory processes.
Main Methods:
- Screening microRNA expression in TNFα-treated adipocytes.
- Analyzing miR-155 expression in genetically modified mice (TNFα knockout, NF-κB pathway manipulation).
- Comparing miR-155 levels in adipose tissue from obese versus normal-weight individuals.
- Investigating miR-155 function via gain and loss-of-function studies in adipocytes.
Main Results:
- miR-155 was identified as the most responsive microRNA to TNFα treatment.
- miR-155 expression is regulated by TNFα and the NF-κB pathway.
- Elevated miR-155 levels were observed in obese subjects' adipose tissue, correlating with TNFα and BMI.
- miR-155 influences adipocyte function, potentially by targeting PPARγ mRNA, and promotes adipocyte inflammation.
Conclusions:
- A pro-inflammatory loop involving NF-κB and miR-155 contributes to amplifying inflammation in adipocytes.
- miR-155 is a key mediator in obesity-associated adipose tissue inflammation.
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