ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Skeletal muscle PGC-1α modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- The effects of 10 months of exercise on circulating ketone body concentration among children.Pediatric research · 2026Article
- The significance of the ketolytic gene OXCT1 in metabolism, intracellular signaling and disease development.Cellular and molecular life sciences : CMLS · 2026Review
- The multifaceted roles of ketones in physiology.Experimental physiology · 2026Review
- The muscle specific MEF2Dα2 isoform promotes muscle ketolysis and running capacity in mice.EMBO reports · 2025Article
- Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats.Iranian journal of basic medical sciences · 2025Article
- The persistence of changes in insulin sensitivity and metabolic gene expression after acute exercise in male and female mice.Current research in physiology · 2025Article
- An AMP-activated protein kinase-PGC-1α axis mediates metabolic plasticity in glioblastoma.Clinical and translational medicine · 2024Article
- Molecular aspects of the exercise response and training adaptation in skeletal muscle.Free radical biology & medicine · 2024Review
- AMPKα2 regulates fasting-induced hyperketonemia by suppressing SCOT ubiquitination and degradation.Scientific reports · 2024Article
- The Impact of Ketone Body Metabolism on Mitochondrial Function and Cardiovascular Diseases.Journal of atherosclerosis and thrombosis · 2023Review
- Molecular control of endurance training adaptation in male mouse skeletal muscle.Nature metabolism · 2023Article
- The molecular athlete: exercise physiology from mechanisms to medals.Physiological reviews · 2023Review
- Transcriptional control of energy metabolism by nuclear receptors.Nature reviews. Molecular cell biology · 2022Review
- The Effects of Exercise Training on Glucose Homeostasis and Muscle Metabolism in Type 1 Diabetic Female Mice.Metabolites · 2022Article
- Review
- PGC-1α deficiency reveals sex-specific links between cardiac energy metabolism and EC-coupling during development of heart failure in mice.Cardiovascular research · 2022Article
- Article
- Hepatocyte-specific fibroblast growth factor 21 overexpression ameliorates high-fat diet-induced obesity and liver steatosis in mice.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Branched-chain amino acid metabolism is regulated by ERRα in primary human myotubes and is further impaired by glucose loading in type 2 diabetes.Diabetologia · 2021Article
- Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery.Frontiers in endocrinology · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ketone bodies (KBs) are crucial energy substrates during states of low carbohydrate availability. However, an aberrant regulation of KB homeostasis can lead to complications such as diabetic ketoacidosis. Exercise and diabetes affect systemic KB homeostasis, but the regulation of KB metabolism is still enigmatic. In our study in mice with either knockout or overexpression of the peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α in skeletal muscle, PGC-1α regulated ketolytic gene transcription in muscle. Furthermore, KB homeostasis of these mice was investigated during withholding of food, exercise, and ketogenic diet feeding, and after streptozotocin injection. In response to these ketogenic stimuli, modulation of PGC-1α levels in muscle affected systemic KB homeostasis. Moreover, the data demonstrate that skeletal muscle PGC-1α is necessary for the enhanced ketolytic capacity in response to exercise training and overexpression of PGC-1α in muscle enhances systemic ketolytic capacity and is sufficient to ameliorate diabetic hyperketonemia in mice. In cultured myotubes, the transcription factor estrogen-related receptor-α was a partner of PGC-1α in the regulation of ketolytic gene transcription. These results demonstrate a central role of skeletal muscle PGC-1α in the transcriptional regulation of systemic ketolytic capacity.-Svensson, K., Albert, V., Cardel, B., Salatino, S., Handschin, C. Skeletal muscle PGC-1α modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice.
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