JAZF1 Inhibits Adipose Tissue Macrophages and Adipose Tissue Inflammation in Diet-Induced Diabetic Mice

Biomed Res Int. 2018 Mar 22:2018:4507659. doi: 10.1155/2018/4507659. eCollection 2018.

Abstract

Background: Juxtaposed with another zinc finger gene 1 (JAZF1) affects gluconeogenesis, insulin sensitivity, lipid metabolism, and inflammation, but its exact role in chronic inflammation remains unclear. This study aimed to examine JAZF1 overexpression in vivo on adipose tissue macrophages (ATMs).

Methods: Mouse models of high-fat diet- (HFD-) induced insulin resistance were induced using C57BL/6J and JAZF1-overexpressing (JAZF1-OX) mice. The mice were randomized (8-10/group) to C57BL/6J mice fed regular diet (RD) (NC group), C57BL/6J mice fed HFD (HF group), JAZF1-OX mice fed RD (NJ group), and JAZF1-OX mice fed HFD (HJ group). Adipose tissue was harvested 12 weeks later. ATMs were evaluated by flow cytometry. Inflammatory markers were evaluated by ELISA.

Results: JAZF1-OX mice had lower blood lipids, blood glucose, body weight, fat weight, and inflammatory markers compared with HF mice (all P < 0.05). JAZF1 overexpression decreased ATM number and secretion of proinflammatory cytokines. JAZF1 overexpression decreased total CD4+ T cells, active T cells, and memory T cells and increased Treg cells. JAZF1 overexpression downregulated IFN-γ and IL-17 levels and upregulated IL-4 levels. JAZF1 overexpression decreased MHCII, CD40, and CD86 in total ATM, CD11c+ ATM, and CD206+ ATM.

Conclusions: JAZF1 limits adipose tissue inflammation by limiting macrophage populations and restricting their antigen presentation function.

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Antigen Presentation
  • Blood Glucose
  • Body Weight
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Co-Repressor Proteins
  • Cytokines / metabolism
  • DNA-Binding Proteins
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / pathology
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Gene Expression
  • Inflammation / etiology*
  • Insulin Resistance / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Random Allocation

Substances

  • Blood Glucose
  • Carrier Proteins
  • Co-Repressor Proteins
  • Cytokines
  • DNA-Binding Proteins
  • JAZF1 protein, mouse
  • Nuclear Proteins