Leucine Supplementation Exacerbates Morbidity in Male but Not Female Mice with Colorectal Cancer-Induced Cachexia

Authors

Eleanor R. Schrems, University of Arkansas, FayettevilleFollow
Wesley S. Haynie, University of Arkansas, FayettevilleFollow
Richard A. Perry Jr., Colorado State UniversityFollow
Francielly Morena, University of Arkansas, FayettevilleFollow
Ana Regina Cabrera, University of Arkansas, FayettevilleFollow
Megan E. Rosa-Caldwell, Harvard UniversityFollow
Nicholas P. Greene, University of Arkansas, FayettevilleFollow
Tyrone A. Washington, University of Arkansas, FayettevilleFollow

Document Type

Article

Publication Date

10-27-2023

Keywords

Biological sex differences; Inflammatory gene expression; Protein imbalance; Anabolic suppression; Muscle wasting

Abstract

Cancer cachexia (CC) is a multifactorial wasting syndrome characterized by a significant loss in lean and/or fat mass and represents a leading cause of mortality in cancer patients. Nutraceutical treatments have been proposed as a potential treatment strategy to mitigate cachexia-induced muscle wasting. However, contradictory findings warrant further investigation. The purpose of this study was to determine the effects of leucine supplementation on skeletal muscle in male and female Apc^Min/+ mice (APC). APC mice and their wild-type (WT) littermates were given normal drinking water or 1.5% leucine-supplemented water (n = 4–10/group/sex). We measured the gene expression of regulators of inflammation, protein balance, and myogenesis. Leucine treatment lowered survival rates, body mass, and muscle mass in males, while in females, it had no effect on body or muscle mass. Leucine treatment altered inflammatory gene expression by lowering Il1b 87% in the APC group and decreasing Tnfa 92% in both WT and APC males, while it had no effect in females (p < 0.05). Leucine had no effect on regulators of protein balance and myogenesis in either sex. We demonstrated that leucine exacerbates moribundity in males and is not sufficient for mitigating muscle or fat loss during CC in either sex in the Apc^Min/+ mouse.

Citation

Schrems, E.R.; Haynie, W.S.; Perry, R.A., Jr.; Morena, F.; Cabrera, A.R.; Rosa-Caldwell, M.E.; Greene, N.P.; Washington, T.A. Leucine Supplementation Exacerbates Morbidity in Male but Not Female Mice with Colorectal Cancer-Induced Cachexia. Nutrients 2023, 15, 4570. https://doi.org/10.3390/nu15214570

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.