Effect of vitamin D3 on lipid droplet growth in adipocytes of mice with HFD‐induced obesity

Abstract Vitamin D‐regulating action of PPARγ on obesity has been confirmed on adipocyte differentiation. However, it is not clear whether vitamin D affects the morphological size of mature adipocytes by influencing the expression of PPARγ in vivo. Our hypothesis was that Vitamin D3 (VitD3) inhibits the growth of adipocyte size by suppressing PPARγ expression in white adipocytes of obese mice. Five‐week‐old male C57BL/6J mice were randomly divided into normal diet and high‐fat diet groups. After 10 weeks, the body weight between the two groups differed by 26.91%. The obese mice were randomly divided into a high‐fat diet, solvent control, low‐dose VitD3 (5000 IU/kg·food), medium‐dose VitD3 (7500 IU/kg·food), high‐dose VitD3 (10,000 IU/kg·food), and PPAR γ antagonist group, and the intervention lasted for 8 weeks. Diet‐induced obesity (DIO) mice fed high‐dose VitD3 exacerbated markers of adiposity (body weight, fat mass, fat mass rate, size of white and brown adipocytes, mRNA, and protein levels of ATGL and Fsp27), and the protein level of ATGL and Fsp27 decreased in the low‐dose group. In conclusion, high‐dose VitD3 possibly via inhibiting the ATGL expression, thereby inhibiting lipolysis, increasing the volume of adipocytes, and decreasing their fat‐storing ability resulted in decreased Fsp27 expression. Therefore, long‐term high‐dose oral VitD3 may not necessarily improve obesity, and we need more clinical trials to explore the intervention dose and duration of VitD3 in the treatment of VitD3 deficiency in obese patients.