TY - JOUR
T1 - Involvement of SIK3 in glucose and lipid homeostasis in mice
AU - Uebi, Tatsuya
AU - Itoh, Yumi
AU - Hatano, Osamu
AU - Kumagai, Ayako
AU - Sanosaka, Masato
AU - Sasaki, Tsutomu
AU - Sasagawa, Satoru
AU - Doi, Junko
AU - Tatsumi, Keita
AU - Mitamura, Kuniko
AU - Morii, Eiichi
AU - Aozasa, Katsuyuki
AU - Kawamura, Tomohiro
AU - Okumura, Meinoshin
AU - Nakae, Jun
AU - Takikawa, Hajime
AU - Fukusato, Toshio
AU - Koura, Minako
AU - Nish, Mayumi
AU - Hamsten, Anders
AU - Silveira, Angela
AU - Bertorello, Alejandro M.
AU - Kitagawa, Kazuo
AU - Nagaoka, Yasuo
AU - Kawahara, Hidehisa
AU - Tomonaga, Takeshi
AU - Naka, Tetsuji
AU - Ikegawa, Shigeo
AU - Tsumaki, Noriyuki
AU - Matsuda, Junichiro
AU - Takemori, Hiroshi
PY - 2012/5/25
Y1 - 2012/5/25
N2 - Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3-/- mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3-/- mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3-/- mice. Lipid metabolism disorders in Sik3-/- mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice.
AB - Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3-/- mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3-/- mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3-/- mice. Lipid metabolism disorders in Sik3-/- mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice.
UR - http://www.scopus.com/inward/record.url?scp=84861473712&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0037803
DO - 10.1371/journal.pone.0037803
M3 - 記事
C2 - 22662228
AN - SCOPUS:84861473712
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e37803
ER -