Differential Immunometabolic Phenotype in Th1 and Th2 Dominant Mouse Strains in Response to High-Fat Feeding

• Published in: PloS one 2015-07, Vol.10 (7), p.e0134089
• Main Authors: Jovicic, Nemanja, Jeftic, Ilija, Jovanovic, Ivan, Radosavljevic, Gordana, Arsenijevic, Nebojsa, Lukic, Miodrag L, Pejnovic, Nada
• Format: Article
• Language: English
• Subjects: Adipose tissue; Animal tissues; Animals; Blood glucose; Body weight; Body weight gain; CD11b antigen; CD11c antigen; CD3 antigen; CD8 antigen; Collagen; CXCR3 protein; Cytokines; Cytokines - metabolism; Dendritic cells; Deposition; Diabetes; Diet; Diet, High-Fat - adverse effects; Enzyme-Linked Immunosorbent Assay; Fatty liver; Fatty Liver - etiology; Fatty Liver - metabolism; Fatty Liver - pathology; Fibrosis; Flow Cytometry; Gene expression; Genetic aspects; Genetic engineering; Glucose; Glucose - metabolism; Glycogen; High fat diet; House mouse; Immunoenzyme Techniques; Inflammation; Inflammation - etiology; Inflammation - metabolism; Inflammation - pathology; Insulin resistance; Interferon; Interleukin 13; Interleukin 6; Intra-Abdominal Fat - immunology; Intra-Abdominal Fat - metabolism; Intra-Abdominal Fat - pathology; Lipids; Liver; Liver Cirrhosis - etiology; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver diseases; Lymphocytes; Lymphocytes T; Macrophages; Male; Medical research; Medicine; Metabolic disorders; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Monocytes; Obesity; Phenotype; Procollagen; Rodents; Species Specificity; Sterols; Studies; T cells; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - pathology; Th2 Cells - immunology; Th2 Cells - metabolism; Th2 Cells - pathology; Transforming growth factors; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0134089

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.