DIFFERENTIAL EFFECTS OF AGE AND OBESITY ON MARKERS OF PROTEIN SYNTHESIS IN HEARTS OF C57BL/6J MICE

Richard A. Perry, Jr., Lemuel A. Brown, David E. Lee, Jacob L. Brown, Megan E. Rosa, Nicholas P. Greene, Tyrone A. Washington, University of Arkansas, Fayetteville, Arkansas; e-mail: rap007@email.uark.edu In 1990, 23.6% of the elderly population (60+ years old) was obese (≥30 BMI). By 2010, it increased to 39.5%. Aging is typically associated with a reduction in lean mass. When this ailment is coupled with the gain in fat mass, the condition is referred to as sarcopenic obesity. Pathological, cardiac hypertrophy is highly associated with both age and obesity. As the prevalence of obesity in the elderly population continues to rise, a firmer understanding of how age and obesity interact to effect cardiac function is needed. PURPOSE: To examine how sarcopenic obesity affects markers of protein synthesis and inhibitors of protein synthesis. METHODS: Twenty-four C57BL/6J mice were evenly distributed into either a normal chow (17% kcals from fat) or high-fat (60% kcals from fat) diet after weaning. Twelve mice from each diet were euthanized at 12-16 weeks of age (young). The remaining 12 were sacrificed at 22-24 months of age (aged). The classification of the 4 groups is as follows: Young Lean (YL), Young Obese (YO), Aged Lean (AL), Aged Obese (AO) (n=6 per group). Whole hearts were excised at time of euthanasia, snap-frozen, and were powdered and processed for use in protein and gene expression assays. Protein expression was measured using western blot. All protein targets are reported as a ratio of phosphorylated to total protein. Gene expression was measured using RT-qPCR. RESULTS: Heart weight:tibia length was increased in the YO and AO by 16% and 29%, respectively, compared to their lean counterparts (p \u3c 0.05). Additionally, AO was 27% greater than YO (p \u3c 0.05). There was a main effect for the obese groups to have approximately 70% higher pAkt/Akt expression compared to aged-matched controls (p \u3c 0.05). There was a main effect for the aged groups to have higher expression of pmTOR/mTOR (p \u3c 0.05). p4EBP-1/4EBP-1 expression was 45% lower in the young obese group compared to the young lean group (p \u3c 0.05). p4EBP-1/4EBP-1 expression was not different within the aged groups. pp70S6K/p70S6K expression was 31% lower in the AO compared to the YO (p \u3c 0.05). There was a main effect for the aged groups (p \u3c 0.05) and a trend for the obese groups (p \u3c 0.09) to have higher gene expression of TNF-α. In young mice, expression of pAMPK/AMPK was ~4-fold higher in the obese group whereas expression in AO was 50% lower than AL. CONCLUSION: Sarcopenic obesity induced differential expression of protein synthesis markers in cardiac muscle. AMPK may be acting as an inhibitor to protein synthesis in the young obese whereas TNF-α may be exerting an inhibitory effect during sarcopenic obesity