Author(s): ZHANG, Y., XIAO, H., YAO, Y., ZU, J., XU, Y., TANG, Q., LU, J., Institution: NANJING SPORT INSTITUTE, Country: CHINA, Abstract-ID: 1218

INTRODUCTION:
Exercise counteracts obesity-induced skeletal muscle ectopic lipid deposition and impaired lipid metabolism. This study aims to examine the effects of an 8-week exercise on skeletal muscle lipid droplet-mitochondrial interaction and key lipid metabolism-related gene expression in obese rats, thereby elucidating the underlying molecular mechanisms.
METHODS:
Fifty-two 5-week-old male Sprague-Dawley rats were acclimatized and randomly divided into standard diet (n=24) and HFFC diet (n=28) groups. After 8 weeks of HFFC feeding (body weight increase >20%), the HFFC group was further divided into control (HC) and exercise (HE) subgroups, each with 14 rats. The standard diet group was assigned to either a control (NC) or exercise (NE) subgroup. The NE and HE groups underwent 8 weeks of treadmill exercise. Lipid deposition was assessed via HE staining, Oil Red O staining, electron microscopy, and triglyceride quantification. The expression of lipid metabolism-related genes was analyzed by immunofluorescence and Western blot.
RESULTS:
1)Compared to the NC group, the HC group showed significant increases in muscle lipid deposition tested by Oil Red O area (+328.09%) and TG content (+543.94%). In contrast, the HE group exhibited reduced muscle Oil Red O area (-48.23%) and TG content (-55.17%) compared to the HC group, along with increased muscle weight (+18.75%) (P<0.05). 2)Electron microscopy analysis revealed that, the HC group contained more and larger lipid droplets, which showed minimal interaction with mitochondria, while the HE group exhibited smaller lipid droplets that were enveloped by mitochondria. 3)Analysis by Western blot and immunofluorescence showed that the HC group showed significantly increased expression of the lipid synthesis proteins CD36(+338.46%) and FAS (+236.36%), a decreased P-HSL/HSL ratio (-32.26%), and elevated colocalization of PLIN2/VDAC(+47.62%), CD36/WGA(+320.07%), and PLIN2/ATGL(+237.9%) vs. the NC group. In contrast, the HE group, relative to the HC group, exhibited markedly reduced CD36 (-84.21%) and FAS (-53.15%) expression but increased P-HSL/HSL ratio (+47.62%) and ATGL (+145.83%) protein levels. Furthermore, colocalization of PLIN2 with VDAC (+216.71%) and ATGL(+243.8%) was further enhanced, while CD36/WGA (-62.08%) colocalization was significantly diminished (P<0.05).
CONCLUSION:
Exercise effectively reduced ectopic lipid deposition, and induced a significant morphological remodeling of lipid droplets, promoting their close physical interaction with mitochondria. These benefits were mediated by a coordinated reprogramming of lipid metabolism, characterized by the suppression of lipid uptake and synthesis, activation of lipolysis to enhance lipid droplet-mitochondria contact and facilitate fatty acid oxidation.