| First Author | Zhang L | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 1713 |
| PubMed ID | 38242911 | Mgi Jnum | J:344957 |
| Mgi Id | MGI:7578510 | Doi | 10.1038/s41598-023-49991-5 |
| Citation | Zhang L, et al. (2024) AMPKalpha2 regulates fasting-induced hyperketonemia by suppressing SCOT ubiquitination and degradation. Sci Rep 14(1):1713 |
| abstractText | Ketone bodies serve as an energy source, especially in the absence of carbohydrates or in the extended exercise. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a crucial energy sensor that regulates lipid and glucose metabolism. However, whether AMPK regulates ketone metabolism in whole body is unclear even though AMPK regulates ketogenesis in liver. Prolonged resulted in a significant increase in blood and urine levels of ketone bodies in wild-type (WT) mice. Interestingly, fasting AMPKalpha2(-/-) and AMPKalpha1(-/-) mice exhibited significantly higher levels of ketone bodies in both blood and urine compared to fasting WT mice. BHB tolerance assays revealed that both AMPKalpha2(-/-) and AMPKalpha1(-/-) mice exhibited slower ketone consumption compared to WT mice, as indicated by higher blood BHB or urine BHB levels in the AMPKalpha2(-/-) and AMPKalpha1(-/-) mice even after the peak. Interestingly, fasting AMPKalpha2(-/-) and AMPKalpha1(-/-) mice exhibited significantly higher levels of ketone bodies in both blood and urine compared to fasting WT mice. . Specifically, AMPKalpha2(DeltaMusc) mice showed approximately a twofold increase in blood BHB levels, and AMPKalpha2(DeltaMyo) mice exhibited a 1.5-fold increase compared to their WT littermates after a 48-h fasting. However, blood BHB levels in AMPKalpha1(DeltaMusc) and AMPKalpha1(DeltaMyo) mice were as same as in WT mice. Notably, AMPKalpha2(DeltaMusc) mice demonstrated a slower rate of BHB consumption in the BHB tolerance assay, whereas AMPKalpha1(DeltaMusc) mice did not show such an effect. Declining rates of body weights and blood glucoses were similar among all the mice. Protein levels of SCOT, the rate-limiting enzyme of ketolysis, decreased in skeletal muscle of AMPKalpha2(-/-) mice. Moreover, SCOT protein ubiquitination increased in C2C12 cells either transfected with kinase-dead AMPKalpha2 or subjected to AMPKalpha2 inhibition. AMPKalpha2 physiologically binds and stabilizes SCOT, which is dependent on AMPKalpha2 activity. |
