Work

Dichloroacetate, a pyruvate dehydrogenase activator, alleviates high‐fat‐induced impairment of myogenic differentiation in skeletal muscles

Year: 2024

Type: article

Abstract: Obesity-induced impairment of myogenic differentiation leads to muscle loss and sarcopenia. Pyruvate dehydrogenase (PDH) plays a crucial role in glucose metabolism and is associated with muscle differentiation. However, the effect of dichloroacetate (DCA), a PDH activator, on obesity-induced impairment of myogenic differentiation remains unknown. Here, we evaluated the effects of DCA treatment on high-fat intake-induced impairment of myogenic differentiation in C2C12 cells and C57BL/6 mice. In C2C12 cells, DCA treatment improved PDH activity that was reduced by palmitate (PAL) and decreased the lactate concentrations in the media. Additionally, DCA reversed PAL- and high-fat diet (HFD)-induced decrease in the expression of myoblast determination protein 1 (MyoD), myogenin (MyoG) and myosin heavy chain (MyHC) in C2C12 cells and C57BL/6 mice. To explore the possible mechanism, DCA treatment restored the levels of p-Akt, p-FoxO1, p-FoxO3a and p-p38 MAPK levels in PAL-treated C2C12 cells. Moreover, the protective effects of DCA were reversed by treatment with the Akt inhibitor MK2206 in C2C12 cells. In summary, DCA treatment alleviated high-fat intake-induced impairment of myogenic differentiation via Akt signalling, suggesting its potential in treating obesity-associated muscle loss and sarcopenia.

Source: Basic & Clinical Pharmacology & Toxicology

DOI: 10.1111/bcpt.14102

Authors: Chuang‐Yen Huang, I‐Shan Han, Po‐Shiuan Hsieh, Min‐Chien Tsai, Hung‐Che Chien

Institutions: Tri-Service General Hospital, National Defense Medical Center

Language: English

Topic: Muscle Physiology and Disorders

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Tri-Service General Hospital, Medical Affairs Bureau