Decrease in αβ/γδ T-cell ratio is accompanied by a reduction in high-fat diet-induced weight gain, insulin...

Area of Science:

• Immunology
• Metabolic Diseases
• Obesity Research

Background:

• The roles of alpha-beta (αβ) and gamma-delta (γδ) T cells in obesity-associated inflammation and insulin resistance (IR) are not fully understood.
• Previous studies on T cell-deficient mice yielded conflicting results regarding high-fat diet (HFD)-induced IR.
• A mouse model overexpressing peroxisome proliferator-activated receptor beta (PPAR-β) in T cells (Tg T-PPAR-β) was previously shown to have partially depleted αβ T cells and a reduced αβ/γδ T-cell ratio.

Purpose of the Study:

• To investigate the impact of a decreased αβ/γδ T-cell ratio on high-fat diet-induced metabolic dysfunction.
• To determine if Tg T-PPAR-β mice are protected against HFD-induced weight gain, insulin resistance, and inflammation.
• To analyze changes in white adipose tissue (WAT) distribution and immune cell composition in these mice.

Main Methods:

• Utilized a transgenic mouse model (Tg T-PPAR-β) with a naturally reduced αβ/γδ T-cell ratio.
• Administered a high-fat diet (HFD) to Tg T-PPAR-β mice and control littermates.
• Assessed body weight, insulin resistance, liver steatosis, WAT mass distribution, and immune cell populations in WAT depots.

Main Results:

• Tg T-PPAR-β mice showed partial protection against HFD-induced weight gain and reduced insulin resistance and liver steatosis, independent of overall weight.
• These mice exhibited altered WAT depot distribution, with increased epididymal WAT mass and decreased subcutaneous WAT mass.
• While total immune cell numbers decreased in WAT depots, γδ T cells were increased in epididymal WAT.

Conclusions:

• Decreasing the αβ/γδ T-cell ratio in white adipose tissue alters its inflammatory state and mass distribution.
• This altered immune cell balance contributes to protection against high-fat diet-induced weight gain, insulin resistance, and inflammation.
• The findings suggest that modulating the αβ/γδ T-cell ratio could be a therapeutic strategy for metabolic diseases.