Vitamin D3 supplementation ameliorates adipose tissue inflammation and adipocyte hypertrophy in type 2 diabetic mice through downregulation of RAGE and SREBP-1c.

Type 2 diabetes is characterized by chronic low-grade inflammation and insulin resistance resulting from activation and infiltration of immune cells into adipose tissue. Vitamin D reportedly exerts an anti-inflammatory effect by regulating immune cell activity and inflammatory cytokine production. This study aimed to investigate the effects of vitamin D supplementation on lymphoid and myeloid immune cell distribution in the adipose tissue and explore the mechanisms by which vitamin D modulates adipose tissue inflammation in diabetes. Five-week-old, male C57BLKS/J-m⁺/m⁺ (CON) and C57BLKS/J-db/db (DB) mice were fed diets containing either 1,000 or 10,000 IU vitamin D/kg diet for 8 weeks. Vitamin D supplementation resulted in a smaller weight gain (33.8% lower), less adipocyte hypertrophy (16.9% lower), and a lower fasting blood glucose concentration (7.4% lower) in DB group. Vitamin D supplementation did not inhibit macrophage and dendritic cell infiltration into adipose tissue; nonetheless, it reduced the percentage of CD8⁺ T cells (18% lower). In DB group, vitamin D supplementation downregulated the gene expression of interleukin 6 (Il6) and CC motif chemokine ligand 2 (Ccl2) in stromal vascular cells (28.2% and 17.3% lower, respectively) as well as that of Il6, Ccl2, sterol regulatory element-binding transcription factor 1 (Srebf1), and advanced glycosylation end product-specific receptor (Ager) in adipose tissue (42.8%, 24.9%, 33.1%, and 58.2% lower, respectively). In conclusion, vitamin D supplementation attenuated the inflammatory response and adipocyte hypertrophy in adipose tissue from diabetic mice. The inhibition of Ager and Srebf1 by vitamin D supplementation potentially contributes to vitamin D's anti-inflammatory and anti-adiposity effects in diabetic mice.