Diabetes, Metabolic Syndrome and Obesity (Sep 2023)

Effects of NKT Cells on Metabolic Disorders Caused by High-Fat Diet Using CD1d-Knockout Mice

  • Ishikawa H,
  • Nagashima R,
  • Kuno Y,
  • Sasaki H,
  • Kohda C,
  • Iyoda M

Journal volume & issue
Vol. Volume 16
pp. 2855 – 2864

Abstract

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Hiroki Ishikawa,1 Ryuichi Nagashima,1 Yoshihiro Kuno,1,2 Hiraku Sasaki,3 Chikara Kohda,1 Masayuki Iyoda1,2 1Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, 142-8555, Japan; 2Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, 142-8666, Japan; 3Department of Health Science, Faculty of Health and Sports Science, Juntendo University, Inzai, Chiba, 270-1695, JapanCorrespondence: Hiroki Ishikawa, Department of Microbiology and Immunology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan, Tel +81-3-3784-8131, Fax +81-3-3784-3069, Email [email protected]: The purpose of this study was to investigate whether NKT cells play an important role in preventing or exacerbating diseases caused by high-fat diet (HFD) using CD1d-knockout (KO) mice which lack NKT cells.Methods: Five-week-old male Balb/c (wild-type; WT) or CD1dKO mice were fed with control-diet (CTD) or HFD for 16 weeks.Results: The present study revealed four main findings. First, CD1dKO mice were susceptible to obesity caused by HFD in comparison to WT mice. Second, clinical conditions of fatty liver caused by HFD were comparable between CD1dKO mice and WT mice. Third, HFD-fed WT mice showed high levels of serum biochemical markers, involved in lipid metabolisms, in comparison to WT mice fed a CTD. Notably, the serum concentrations of ALT, T-CHO, TG and HDL-C in CD1dKO mice fed a HFD were almost comparable to those of CD1dKO mice fed a CTD. Fourth, the expression of peroxisome proliferator-activated receptor (PPAR) γ, low-density lipoprotein receptor (LDLR), CD36 of epididymal adipose tissue enhanced and proprotein convertase subtilisin/kexin type (PCSK) 9 in serum decreased.Conclusion: NKT cells were responsible for protection against HFD-induced obesity. However, CD1dKO mice were resistant to serum biochemical marker abnormalities after HFD feeding. One possible explanation is that the epididymal adipose tissue of CD1dKO mice could take up greater amounts of excess lipids in serum in comparison to WT mice.Keywords: NKT cells, high-fat diet, obesity, serum biochemical markers, adipose tissue

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