Editing Α-Ketoglutaric acid (section)

====Resistance exercise, obesity, and muscle atrophy====
Resistance exercise is exercising a muscle or muscle group against external resistance (see [[strength training]]). Studies have found that: '''a)''' mice feeding on a high fat or normal diet and given the resistance exercise of repeatedly climbing up a 1 [[meter]] ladder for 40 minutes had higher levels of α-ketoglutarate in their blood and seven muscles than non-exercising mice feeding respectively on the high fat or normal diet; '''b)''' mice conducting ladder climbing for several weeks and eating a high fat diet developed lower fat tissue masses and higher lean tissue masses than non-exercising mice on this diet; '''c)''' mice not in exercise training fed α-ketoglutarate likewise developed lower fat tissue and higher lean tissue masses than α-ketoglutarate-unfed, non-exercising mice; '''d)''' OXGR1 was strongly expressed in the mouse [[Renal medulla|adrenal gland inner medullas]] and either resistance training or oral α-ketoglutarate increased this tissue's levels of the [[mRNA]] that is responsible for the synthesis of OXGR1; '''e)''' α-ketoglutarate stimulated [[chromaffin cells]] isolated from mouse adrenal glands to release [[epinephrine]] but reduction of these cells' OXGR1 levels by [[small interfering RNA]] reduced this response; '''f)''' α-ketoglutarate increased the blood serum levels of epinephrine in mice expressing OXGR1 but not in ''Oxgr1'' gene knockout mice (i.e., mice lacking the ''OXGR1'' gene and protein); '''g)''' mice on the high fat diet challenged with α-ketoglutarate increased their blood serum levels of epinephrine and developed lower fat tissue masses and higher lean tissue masses but neither ''OXGR1'' gene knockout mice nor mice that had only their adrenal glands' ''OXGR1'' gene knocked out showed these responses; and '''h)''' ''OXGR1'' gene knockout mice fed the high fat diet developed muscle protein degradation, muscle [[atrophy]] (i.e., wasting), and falls in body weight whereas control mice did not show these fat diet-induced changes. These findings indicate that in mice resistance exercise increases muscle production as well as serum levels of α-ketoglutarate which in turn suppresses diet-induced obesity (i.e., low body fat and high lean body masses) at least in part by stimulating the OXGR1 on adrenal gland chromaffin cells to release epinephrine.<ref name="pmid32104923"/><ref name="pmid35507647"/><ref name="pmid28939592">{{cite journal | vauthors = Cai X, Yuan Y, Liao Z, Xing K, Zhu C, Xu Y, Yu L, Wang L, Wang S, Zhu X, Gao P, Zhang Y, Jiang Q, Xu P, Shu G | title = α-Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway | journal = FASEB Journal | volume = 32 | issue = 1 | pages = 488–499 | date = January 2018 | pmid = 28939592 | pmc = 6266637 | doi = 10.1096/fj.201700670R | doi-access = free | url = }}</ref> Another study reported that middle‐aged, i.e., 10‐month‐old, mice had lower serum levels of α-ketoglutarate than 2‐month‐old mice. Middle aged mice fed a high fat diet gained body weight and fat mass in the lower parts of their bodies and had impaired glucose tolerance as defined in glucose tolerance tests. Adding α-ketoglutarate to the drinking water of these mice inhibited the development of these changes. These results suggest that drinking the α-ketoglutarate-rich water replenished the otherwise diminished supplies of α-ketoglutarate in middle aged mice; the replenished supply of α-ketoglutarate thereby became available to suppress obesity and improve glucose tolerance.<ref name="pmid31691468">{{cite journal | vauthors = Tian Q, Zhao J, Yang Q, Wang B, Deavila JM, Zhu MJ, Du M | title = Dietary alpha-ketoglutarate promotes beige adipogenesis and prevents obesity in middle-aged mice | journal = Aging Cell | volume = 19 | issue = 1 | pages = e13059 | date = January 2020 | pmid = 31691468 | pmc = 6974731 | doi = 10.1111/acel.13059 | url = }}</ref> Finally, a study in rats feed a low fat or high fat diet for 27 weeks and drinking α-ketoglutarate-rich water for the last 12 weeks of this 27 week period decreased their fat issue masses and increased their whole-body insulin sensitivity as defined in glucose tolerance tests. Rats fed either of these diets but not given α-ketoglutarate-rich water did not show these changes. This study indicates that α-ketoglutarate regulates body fat mass and insulin sensitivity in rats as well as mice.<ref name="pmid31357871">{{cite journal | vauthors = Tekwe CD, Yao K, Lei J, Li X, Gupta A, Luan Y, Meininger CJ, Bazer FW, Wu G | title = Oral administration of α-ketoglutarate enhances nitric oxide synthesis by endothelial cells and whole-body insulin sensitivity in diet-induced obese rats | journal = Experimental Biology and Medicine | volume = 244 | issue = 13 | pages = 1081–1088 | date = October 2019 | pmid = 31357871 | pmc = 6775570 | doi = 10.1177/1535370219865229 | url = }}</ref>