2. Academic Validation
  3. Knockout of ICAT in Adipose Tissue Alleviates Fibro-inflammation in Obese Mice

Knockout of ICAT in Adipose Tissue Alleviates Fibro-inflammation in Obese Mice

  • Inflammation. 2022 Oct 1. doi: 10.1007/s10753-022-01742-w.
Zhuan Song 1,  Ning Liu 1 2,  Yu He 1,  Jingqing Chen 3,  Jun Li 1,  Fengchao Wang 4,  Zhenlong Wu 5 6
Affiliations

Affiliations

  • 1 Department of Animal Nutrition and Feed Science, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China.
  • 2 Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100193, China.
  • 3 Laboratory Animal Center of the Academy of Military Medical Sciences, Beijing, 100193, China.
  • 4 National Institute of Biological Sciences (NIBS), Beijing, 102206, China.
  • 5 Department of Animal Nutrition and Feed Science, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China. [email protected].
  • 6 Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100193, China. [email protected].
PMID: 36181623 DOI: 10.1007/s10753-022-01742-w
Abstract

The E2 promoter binding factor 1 (E2F1) and the Wnt/β-catenin signaling are crucial in regulating metabolic homeostasis including obesity. The β-catenin interacting protein 1 (CTNNBIP1), also known as the inhibitor of β-catenin and TCF4 (ICAT), is required for E2F1 to inhibit the activity of β-catenin. However, the role of ICAT in E2F1 regulating obesity-related metabolic disorders remains unknown. In the present study, male adipose tissue-specific ICAT knockout (ICATadi-/-) C57BL/6 J mice and control littermates aged 6-8 weeks were fed with high-fat diet (HFD) for 12 weeks to explore the effect of ICAT on lipid metabolism and obesity-related disorders. Results showed that the adipose tissue-specific ICAT knockout had negligible effect on lipid metabolism, reflected by no difference in body weight, fat mass, and the expression of proteins involved in lipid metabolism in white adipose tissue (WAT) and the liver between the ICATadi-/- mice and the control littermate (ICATfl/fl) mice. However, the knockout of ICAT reduced inflammatory response in WAT and the liver. Additionally, Sirius red staining results showed that deletion of ICAT attenuated fibrosis and reduced mRNA levels of transforming growth factor β1(TGF-β1), matrix metallopeptidase 2 (Mmp2), Mmp3, and collagen, type V, alpha 1 (Col5a1) in WAT and the liver. These results suggested that knockout of ICAT improved the metabolic abnormalities of obese mice through attenuating adipose tissue and the liver inflammation as well as fibrosis. Our findings may provide a new insight to understand the role of ICAT in inflammation and fibrosis.

Keywords

E2F1; Fibrosis; ICAT; Inflammatory response; Obesity..

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