Aerobic Exercise Attenuates Intramyocellular Lipid Accumulation by Upregulating Vitamin D Receptor.

Vitamin D deficiency is a global public health problem associated with intramyocellular lipid (IMCL) accumulation, leading to insulin resistance. Aerobic exercise improves lipid metabolism, insulin sensitivity, and vitamin D levels. However, the mechanism by which aerobic exercise regulates IMCL remains unclear. C57BL/6J male mice were randomly divided into four groups: control (CON), vitamin D-deficient (VDD), control exercise, and vitamin D-deficient exercise (VDDE). Moreover, we generated skeletal muscle-specific vitamin D receptor (VDR)-knockout (mVDR^-/-) mice and classified them into four groups: VDR^flox/flox control (FC); mVDR^-/-; exercise and VDR^flox/flox control; and exercise and mVDR^-/- (emVDR^-/-). All exercise mice underwent a 12-week aerobic exercise program on a treadmill at speeds progressively increasing from 10 to 17 m/min. The VDD group mice exhibited decreased VDR expression, lipolysis factors (ATGL and Hormone-sensitive lipase (HSL)), and fatty acid oxidation (SIRT1 and PGC1α), and increased expression of lipid synthesis factors (DGAT1 and FATP1) compared with the CON group. Conversely, the VDDE group mice showed a significant increase in VDR, ATGL, HSL, SIRT1 and PGC1α expression, alongside a decrease in DGAT1, DGAT2, FATP1 and CD36 expression compared with the VDD group. Moreover, mVDR^-/- mice exhibited impaired lipid metabolism (FATP1, CD36, SREBP1C, DGAT1, DGAT2 and ATGL) and fatty acid oxidation (SIRT1 and PGC1α) compared with the FC group mice. However, emVDR^-/- mice did not show improved lipid metabolism or fatty acid oxidation related factors compared with mVDR^-/- mice. Therefore, aerobic exercise attenuates IMCL accumulation may by upregulating VDR associated with restored SIRT1/PGC1α signaling mediated lipid metabolism in skeletal muscle.