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The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
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Bckdk-Mediated Branch Chain Amino Acid Metabolism Reprogramming Contributes to Muscle Atrophy during Cancer Cachexia.

Li Chen1, Hong Zhang1, Mengyi Chi1

  • 1Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.

Molecular Nutrition & Food Research
|December 27, 2023
PubMed
Summary
This summary is machine-generated.

Branched-chain amino acid (BCAA) metabolic dysfunction accelerates cancer cachexia. Supplementing BCAAs improves survival by promoting protein synthesis and inhibiting degradation in affected muscles.

Keywords:
Bckdkbranch chain amino acidcancer cachexiametabolismskeletal muscle

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • Branched-chain amino acids (BCAAs) are essential nutrients vital for energy and protein metabolism.
  • BCAA metabolic dysfunction is implicated in various physiological conditions, including muscle wasting.

Purpose of the Study:

  • To investigate the role of BCAA metabolic dysfunction in cancer cachexia.
  • To explore the therapeutic potential of BCAA supplementation in mitigating muscle wasting.

Main Methods:

  • Generation of muscle-specific Bckdk conditional knockout (cKO) mice.
  • Establishment of a cancer cachexia model using Lewis lung cancer (LLC) tumor transplantation.
  • Analysis of protein synthesis and degradation pathways in skeletal muscle.

Main Results:

  • Muscle-specific Bckdk-cKO mice exhibited accelerated cancer cachexia with increased protein ubiquitination and impaired synthesis.
  • BCAA supplementation in cKO mice bearing LLC tumors improved survival and ameliorated cachexia.
  • BCAA supplementation promoted protein synthesis and inhibited protein degradation in skeletal muscle.

Conclusions:

  • Dysfunctional BCAA metabolism exacerbates muscle wasting in cancer cachexia.
  • Reprogramming BCAA catabolism via supplementation offers a therapeutic strategy to preserve muscle mass.