An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice.
Induction of heat shock protein (HSP)72 improves insulin resistance and obesity in diabetic animal models. Geranylgeranylacetone (GGA), known as an antiulcer drug, induces HSP72 and protects organs against several cellular stresses. This study investigated whether GGA administration would induce HSP72 in liver and render physiological protection against high-fat feeding in mice. A single and 4-wk oral administration of 200 mg/kg GGA was performed in high-fat diet (HFD)-fed mice. Metabolic parameters, cytokines, and gene expressions related to insulin signaling were evaluated. A single administration of GGA induced HSP72 in liver of normal chow-fed and HFD-fed mice. Insulin resistance after HFD was slightly ameliorated. Four weeks of GGA administration also increased HSP72 in liver and significantly improved insulin resistance and glucose homeostasis upon glucose challenge. Activation of c-jun NH₂-terminal kinase (JNK) was attenuated, and insulin signaling was improved in the liver of HFD mice. Visceral adiposity was decreased in GGA-treated mice, accompanied by reduced leptin and increased adiponectin levels. GGA can be a novel therapeutic approach to treat metabolic syndrome as well as type 2 diabetes by improving insulin signaling and reducing adiposity. These beneficial effects of GGA could be mediated through HSP72 induction and JNK inactivation in the liver.
Adachi
Hironori
H
Dept. of Metabolic Medicine, Kumamoto University, Honjo, Japan.
Kondo
Tatsuya
T
Ogawa
Rei
R
Sasaki
Kazunari
K
Morino-Koga
Saori
S
Sakakida
Michiharu
M
Kawashima
Junji
J
Motoshima
Hiroyuki
H
Furukawa
Noboru
N
Tsuruzoe
Kaku
K
Miyamura
Nobuhiro
N
Kai
Hirofumi
H
Araki
Eiichi
E
D052242:Adiponectin / Q000502:physiology; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D004224:Diterpenes / Q000494:pharmacology*; D004435:Eating / Q000502:physiology; D005951:Glucose Tolerance Test; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D020738:Leptin / Q000502:physiology; D008099:Liver / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects
D052242:Adiponectin; D001786:Blood Glucose; D004224:Diterpenes; D050884:HSP72 Heat-Shock Proteins; D007328:Insulin; D020738:Leptin; C031049:geranylgeranylacetone