Reduced intake of carbohydrate prevents the development of obesity and impaired glucose metabolism in ghrelin O-acyltransferase knockout mice.
A close relationship between acylated-ghrelin and sucrose intake has been reported. However, little has been examined about the physiological action of ghrelin on preference for different types of carbohydrate such as glucose, fructose, and starch. The current study was aimed to investigate the role of acylated-ghrelin in the determinants of the choice of carbohydrates, and pathogenesis of chronic disorders, including obesity and insulin resistance. In a two-bottle-drinking test, ghrelin O-acyltransferase (GOAT) knockout (KO) mice consumed a less amount of glucose and maltodextrin, and almost the same amount of fructose and saccharin solution compared to WT littermates. The increased consumption of glucose and maltodextrin was observed when acylated-ghrelin, but not unacylated-ghrelin, was exogeneously administered in normal C57BL/6J mice, suggesting an association of acylated-ghrelin with glucose-containing carbohydrate intake. When fed a diet rich in maltodextrin, starch and fat for 12 weeks, GOAT KO mice showed less food intake and weight gain, as well as improved glucose tolerance and insulin sensitivity than WT mice. Our data suggests that blockade of GOAT activity may offer a therapeutic option for treatment of obesity and its associated metabolic syndrome by preventing from overconsumption of carbohydrate-rich food.
Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan. Electronic address: tetsuya.kouno@shionogi.co.jp.
Tetsuya
T
Kouno
Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Nobuteru
N
Akiyama
Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Kumiko
K
Fujieda
Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Isamu
I
Nanchi
Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Tomohiko
T
Okuda
Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Takanori
T
Iwasaki
Department of Biological Chemistry, Human Health Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Shogo
S
Oka
Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Hideo
H
Yukioka
D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D050154:Adiposity; D000284:Administration, Oral; D000818:Animals; D050260:Carbohydrate Metabolism; D004035:Diet Therapy; D059305:Diet, High-Fat / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D002149:Energy Intake; D054439:Ghrelin / Q000494:pharmacology / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
D004040:Dietary Carbohydrates; D054439:Ghrelin; D008565:Membrane Proteins; D000217:Acyltransferases; C526983:Mboat4 protein, mouse; D005947:Glucose
Body weight; Carbohydrate; Food intake; Ghrelin