The Effects of Leucine Supplementation on Skeletal Muscle Mitochondrial Content and Protein Turnover in Tumor Bearing Mice

Abstract

IntroductionMany forms of cancer are associated with loss of lean body mass, a significant indicator of increased mortality. This effect is commonly attributed to decreased protein synthesis and stimulation of proteolytic pathways within the skeletal muscle due to metabolic disturbances from the tumor burden. The branched chain amino acid (BCAA) leucine has been shown to improve protein synthesis, insulin signaling, and mitochondrial biogenesis, key signaling pathways influenced by tumor signaling.PurposeOur study aimed to elucidate the effects of leucine supplementation on mitochondrial biogenesis, within the Lewis Lung Carcinoma (LLC) implantation model. We hypothesized that LLC implantation will impair mitochondrial biogenesis and protein synthesis leading to a loss of muscle mass, with leucine attenuating these effects.MethodsTwenty male C57BL/6 mice were divided into four equal groups (n=5) of equivalent body weight: Chow, leucine (Leu), LLC, LLC+Leu. At the age of 9–10 weeks, mice received a subcutaneous injection of 1×106 LLC cells or phosphate buffered saline (PBS). Leu groups were then switched to diet supplemented with 5% leucine (w/w). Upon euthanasia, muscle and tumors were weighed and collected. Measures of protein synthesis, mitochondrial biogenesis, and inflammation in the gastrocnemius muscle were assessed via western blot analysis.ResultsWhile body mass was not different between groups, gastrocnemius mass was decreased in the LLC+Leu group relative to the LLC group (p=0.040). Protein synthesis, quantified through the SUnSET technique, was decreased in LLC mice (p=0.001). Phosphorylation of STAT3, an indicator of inflammation was decreased in the Leu group relative to the control (p=0.019), but did not significantly attenuate the inflammatory effect of LLC implantation (p=0.619). Peroxisome proliferator‐activated receptor Gamma Co‐activator 1‐α (PGC‐1α), a marker of mitochondrial biogenesis, was increased in LLC+Leu relative to LLC (p=0.001). Finally, LLC implantation decreased mitochondrial content as measured by Cytochrome C (p=0.015), mitochondrial complexes III (p=0.006) and V (p=0.041).ConclusionWithin our study, leucine supplementation was unable to preserve protein synthesis or mitochondrial content associated with LLC implantation. However, Leucine supplementation was able to increase mitochondrial biogenesis signaling.Support or Funding InformationUniversity of Memphis School of Health Studies Faculty GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.