Accumulation of lipids after acute direct and indirect traumatic injuries in male and female mice.

Background: Adipose infiltration and lipid droplet accumulation are implicated in metabolic diseases and are known to limit skeletal muscle repair and regeneration. However, their role in skeletal muscle injury, particularly volumetric muscle loss (VML), remains unclear. We aimed to characterize early lipid and adipokine responses following direct (i.e., VML) and indirect (i.e., denervation) traumatic injuries.

Methods: Adult male and female C57Bl/6J mice (n = 36) were randomized to VML injury to the posterior hindlimb, tibial nerve denervation, or remained injury Naïve. Three days post, in vivo muscle function was assessed. Serum and gastrocnemius muscle tissue were assessed for histological and biochemical analyses.

Results: A decrease in total myofiber number occurred post-VML with a reduction in force and increased fatigue. Lipid droplet-associated proteins displayed injury- and myofiber type-specific changes, with VML exhibiting accumulation of perilipin 5 localized to the injury site. Lipid droplets in the muscle remaining were significantly greater post-VML compared to denervation. The pro-inflammatory adipokine IL-6 and growth factor IGF-1 were markedly increased in the muscle remaining post-VML, while circulating metabolic regulators, adiponectin and leptin, were suppressed.

Conclusions: These findings underscore lipid droplet dynamics and adipokine signaling disruptions following indirect and direct traumatic injuries in a preclinical model. Future work should be done to explore aspects of lipid droplet regulation temporally following skeletal muscle injuries, as early accumulation may suggest an additional etiology in the pathological sequelae of injury.