title: Differential Immunometabolic Phenotype in Th1 and Th2 Dominant Mouse Strains in Response to High-Fat Feeding.
abstract: Immune reactivity plays an important role in obesity-associated metabolic disorders. We investigated immunometabolic phenotype of C57Bl/6 and BALB/c mice, prototypical Th1 and Th2-type strains, fed chow or high-fat diet (HFD) for 24 weeks. In comparison to C57Bl/6 mice, chow-fed BALB/c mice had higher body weight and weight gain, lower glycemia, more pronounced liver steatosis, but less inflammation and collagen deposition in liver. In response to HFD C57Bl/6 mice exhibited higher weight gain, higher glycemia, HbA1c and liver glycogen content, increased amount of visceral adipose tissue (VAT) and number of VAT associated CD3+CXCR3+ T cells, CD11c+ dendritic cells (DCs) and F4/80+ macrophages than BALB/c mice. More numerous CD3+ and CD8+ T lymphocytes, myeloid DCs, proinflammatory macrophages (F4/80+CD11b+CD11+ and F4/80+IL-1β+) and CD11b+Ly6Chigh monocytes and higher levels of proinflammatory IL-6, TNF-α and IFN-γ were present in liver in HFD-fed C57Bl/6 mice compared with diet-matched BALB/c mice. As opposed to C57Bl/6 mice, HFD induced marked liver steatosis and upregulated the hepatic LXRα and PPARγ genes in BALB/c mice. C57Bl/6 mice fed HFD developed liver fibrosis and increased hepatic procollagen and TGF-β mRNA expression, and IL-33, IL-13 and TGF-β levels in liver homogenates, while BALB/c mice fed HFD had scarce collagen deposition in liver. The obtained results suggest inherent immunometabolic differences in C57Bl/6 and BALB/c mice. Moreover, HFD Th1-type mice on high fat diet regimen are more susceptible to adiposity, liver inflammation and fibrosis, while Th2-type mice to liver steatosis, which is associated with differential immune cell composition in metabolic tissues. Strain-dependent differences in immunometabolic phenotype may be relevant for studies of obesity-associated metabolic diseases in humans.
authors.affiliation: Center for Molecular Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; Institute of Histology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Jovicic
authors.affiliation: Center for Molecular Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; Institute of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Ilija
authors.initials: I
authors.lastname: Jeftic
authors.affiliation: Center for Molecular Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Jovanovic
authors.affiliation: Center for Molecular Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Radosavljevic
authors.affiliation: Center for Molecular Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Arsenijevic
authors.affiliation: Center for Molecular Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Miodrag L
authors.initials: ML
authors.lastname: Lukic
authors.affiliation: Center for Molecular Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; Institute of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Nada
authors.initials: N
authors.lastname: Pejnovic
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D016207:Cytokines; D005947:Glucose