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Endocrine Abstracts (2013) 32 OC6.5 | DOI: 10.1530/endoabs.32.OC6.5

1Department of Internal Medicine III, Dresden University of Technology, Dresden, Germany; 2Institute of Physiology, Dresden University of Technology, Dresden, Germany; 3Developmental Biology Section, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.


Introduction: Macrophages and lymphocytes are considered as major players in adipose tissue (AT) inflammation and liver steatosis, contributing to metabolic dysregulation during obesity. The costimulatory molecules B7.1 and B7.2 are important regulators of T-cell activation and inflammatory reactions, however, their contribution in obesity-related AT and liver low-grade inflammation is poorly characterized.

Methods: Mice sufficient or deficient in B7.1 and B7.2 (double knockouts, Dko) were fed a low or high-fat diet (HFD) for 18 weeks. Body weight was measured weekly and metabolic functions were assessed by measuring blood glucose, cholesterol, triglycerides, insulin, leptin, adiponectin and performing glucose and insulin tolerance tests. Subcutaneous and gonadal AT were excised and the stromal vascular fraction (SVF) was analyzed by FACS. Liver steatosis was evaluated by measuring intratissular triglycerides and confirmed by H&E and Oil-Red stainings. Liver non-parenchymal cells were isolated and analysed by FACS. The levels of inflammation, thermogenesis and fat deposition genes were measured by qPCR in white and brown adipose tissue and liver respectively.

Results: B7.1 and B7.2 expression was upregulated in gonadal AT and SVF upon HFD. Dko mice displayed higher glucose, cholesterol and leptin levels and worse GTT when fed a HFD compared to the B7.1/B7.2 sufficient mice. This was accompanied by downregulation of Tregs, CD4 and CD8 lymphocytes and a parallel upregulation of proinflammatory M1 macrophages (defined as F4/80+CD11b+CD11c+ or F4/80+CD11c+CD206-cells) in both subcutaneous and gonadal AT. Dko mice showed also increased liver steatosis, linked with increased levels of inflammatory M1-like macrophages and reduced levels of Tregs in the liver. In accordance, Dko mice had higher levels of inflammation and fat accumulation genes in AT and liver respectively and lower levels of UCP-1 in the brown AT.

Conclusion: The B7.1-B7.2 signalling pathways are significant regulators of the obesity-related adipose tissue inflammation and liver steatosis pathophysiology.

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