(959.6) Use of the Lipolysis Inhibitor Acipimox Fails to Modulate Chronic Muscle Protein Synthesis Rates or Attenuate the Loss of Muscle Mass in a Rodent Model of Severe Burns

Poster Board Number: E605

Emre Vardarli (University of Texas Medical Branch at Galveston), Nisha Bhattarai (University of Texas Medical Branch at Galveston), Doaa Abdelrahman (University of Texas Medical Branch at Galveston), Amina El-Ayadi (University of Texas Medical Branch at Galveston), Andrew Murton (University of Texas Medical Branch at Galveston)

Objective: Massive burns result in chronic lipolysis of adipose stores resulting in ectopic lipid accumulation. Given reports that hyperlipidemia and/or increased intramyocellular lipid accumulation is associated with impaired synthesis of muscle proteins, we hypothesized that administering the lipolysis inhibitor acipimox could protect muscle protein synthesis capacity in a rodent model of burns, thereby blunting the loss of muscle mass.

Methods: Sprague Dawley rats (4 groups, 16 animals per group, n = 64) were randomized to receive a scald burn (~ 60 % total body surface area; n=32) or sham procedure. Animals in each group were assigned to receive either vehicle (saline) or acipimox (50 mg/kg/day) daily by i.p. injection for 7 days. All animals received a bolus of deuterated water (10 ml/kg, i.p.) followed by supplementation in drinking water (2 %) to monitor habitual muscle protein synthesis rates (MPS). On day 7, animals were sacrificed, and tissues collected. MPS was calculated by measuring intracellular and bound deuterium enrichment of alanine via Gas Chromatography Isotope Ratio Mass Spectrometry.

Results: Severe burns resulted in significant body weight loss compared to the sham injury group (7 % vs 10 %; p lt; 0.001). However, acipimox administration did not prevent the loss of body weight. There was a trend for gastrocnemius and tibialis anterior muscle weights to be lower in burn animals (P = 0.058 and P=0.057, respectively). However, acipimox did not prevent the loss of muscle weight with burn injury. Neither burn injury nor acipimox administration impacted habitual MPS rates.

Conclusion: In sharp contrast to what is observed in patients, severe burns do not alter habitual MPS rates in rats. Given evidence that rats still experience a loss of muscle mass in response to thermal injury, it suggests that the dominant mechanism by which muscle protein content declines in these animals is via enhanced muscle proteolysis. Acipimox appears to exert no beneficial impact on muscle protein homeostasis in burn injured rodents.

Support or Funding Information

Shriners Hospitals for Children Developmental Grant