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Effect of Genetically Decreased BCAA Concentration on Glucose Tolerance in Mice
Ist Teil von
Annals of nutrition and metabolism, 2019-01, Vol.75, p.306
Ort / Verlag
Basel: S. Karger AG
Erscheinungsjahr
2019
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
Background/Aims: Branched-chain amino acids (BCAAs) are essential amino acids for building proteins, and also exist as free amino acids to play an important role for regulating protein and glucose metabolism. The concentrations of free BCAAs are tightly regulated by the BCAA catabolic pathway in which the first two steps are common for three BCAAs. The second step is the ratelimiting step in which branched-chain alpha-keto acids (BCKAs) are oxidatively decarboxylated by BCKA dehydrogenase (BCKDH) to form branched-chain acyl-CoAs. The BCKDH activity is regulated by BCKDH kinase (BDK) which causes inactivation. Methods: Recently, we generated the BDK knock-out (KO) mice and showed the BCKDHs in several tissues were fully activated and the plasma BCAA concentrations were decreased to less than 50% of the control mice. We confirmed the BDK-KO mice showed neurological defects as the previous report, and also found deteriorated glucose tolerance by feeding either control or high-fat diet (HFD). We also produced the muscle- or adipose tissue-specific BDK knock-out (BDK-mKO or adKO) mice to find out which tissue is responsible for the phenotype. Results: The both BDK-mKO and adKO mice fed control diet showed no abnormalities in glucose tolerance, indicating that other tissue's BCAAs are involved in maintaining normal glucose metabolism. However the HFD-fed BDK-adKO, but not mKO mice, got worse glucose tolerance than control mice, which was ameliorated by giving the drinking water with 3% BCAA. Conclusions: These results suggest that adipose tissue is responsible for deterioration of HFD-induced glucose intolerance by decreased BCAA concentrations.