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Effects of NKT Cells on Metabolic Disorders Caused by High-Fat Diet Using CD1d-Knockout Mice
Hiroki Ishikawa1, Ryuichi Nagashima1, Yoshihiro Kuno1,2
1Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, 142-8555, Japan.
Purpose:
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.
Insights
Natural killer T (NKT) cells protect against high-fat diet (HFD)-induced obesity. However, mice lacking NKT cells showed resistance to HFD-induced metabolic abnormalities, suggesting a complex role in diet-related diseases.
Area of Science:
- Immunology
- Metabolic Diseases
- Dietary Research
Background:
- High-fat diets (HFD) are linked to obesity and metabolic dysfunction.
- The role of Natural Killer T (NKT) cells in diet-induced diseases is not fully understood.
Purpose of the Study:
- To investigate the role of NKT cells in high-fat diet (HFD)-induced obesity and related diseases.
- To use CD1d-knockout (KO) mice, which lack NKT cells, to elucidate their function.
Main Methods:
- Balb/c (wild-type; WT) and CD1d-knockout (KO) mice were fed a control diet (CTD) or HFD for 16 weeks.
- Evaluated obesity, fatty liver, serum biochemical markers (lipid metabolism), and gene expression in adipose tissue.
Main Results:
- CD1dKO mice exhibited increased susceptibility to HFD-induced obesity compared to WT mice.
- Fatty liver conditions were similar between CD1dKO and WT mice on HFD.
- HFD-fed WT mice showed elevated lipid metabolism markers; CD1dKO mice on HFD had comparable markers to CTD-fed CD1dKO mice.
- Upregulated expression of PPARγ, LDLR, CD36 in epididymal adipose tissue and decreased PCSK9 in serum of CD1dKO mice on HFD.
Conclusions:
- NKT cells are crucial for preventing HFD-induced obesity.
- Mice lacking NKT cells (CD1dKO) were resistant to HFD-induced serum biochemical abnormalities.
- Enhanced lipid uptake by epididymal adipose tissue in CD1dKO mice may explain their resistance to metabolic derangements.
