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Obesity is a major public health crisis worldwide.This study was conducted to test the beneficial effect of a-ketoglutarate (a-KG) in obesity objects.Male Sprague-Dawley rats were fed for 15 wk a high-fat (40% energy) beginning at 4 wk of age,resulting in 30% higher body weight gains higher weights in HF than normal fed rats.Starting at 19 wk of age,the rats will continue to be fed their diets and receive drinking water containing o or 1% a-KG (n = 8 per group) for 10 weeks.Water consumption was measured daily.Food intake and body weights were recorded weekly.At the end of trial,venous blood samples from tail were obtained for metabolite analysis,whereas gastrocnemius muscle were weight and collected to determine the abundance and phosphorylation state of the mammalian target of the rapamycin (mTOR),ribosomal protein S6 kinase l (S6KI) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BPl).In addition,Retroperitoneal (RP),epididymal (EP),subcutaneous (SC; inguinal),and mesenteric (MT) fat tissues,as well as brown adipose tissue (located in the interscapular region),brain,kidney,and other tissues were dissected and weighed.The data indicated that l% a-KG supplementation had no effect on adipose tissue,but increased (P<0.05) gastrocnemius muscle weight compared to control group.Consistent with these data,the addition of l% a-KG increased (P<0.05) the phosphorylated levels of mTOR and 4E-BPl proteins.Interestingly,in present study the data showed that a-KG supplementation decreased (P<0.05) the leucine level in plasma.Collectively,our finding may provide new clues for nutritional or pharmacological strategies to treat obese subjects.