Defective muscle ketone body oxidation disrupts BCAA catabolism by altering mitochondrial branched-chain aminotransferase

Author:

Mechchate Hamza1,Abdualkader Abdualrahman Mohammed1,Bernacchi James Bradshaw1,Gopal Keshav23,Tabatabaei Dakhili S. Amirhossein23,Yang Kunyan23ORCID,Greenwell Amanda A.23ORCID,Kong Xingxing4,Crawford Peter A.56,Al Batran Rami1ORCID

Affiliation:

1. Faculté de Pharmacie, Université de Montréal, Montreal, Quebec, Canada

2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

3. Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada

4. State Key Laboratory of Genetic Engineering and School of Life Sciences, Fudan University, Shanghai, China

5. Division of Molecular Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States

6. Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States

Abstract

Most studies investigated ketone body metabolism under pathological conditions, whereas the role of ketone body metabolism in regulating normal physiology has been relatively understudied. To address this gap, we used lean mice lacking muscle ketone body oxidation enzyme SCOT. Our work demonstrates that deleting muscle SCOT has no impact on glucose and fat metabolism in lean mice, but it disrupts muscle BCAA catabolism and causes an accumulation of BCAAs by altering BCATm.

Funder

Kidney Foundation of Canada

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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