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PI3K-resistant GSK3 controls adiponectin formation and protects from metabolic syndrome
- Source :
- Proc. Natl. Acad. Sci. U.S.A. 113, 5754-5759 (2016)
- Publication Year :
- 2016
-
Abstract
- Metabolic syndrome is characterized by insulin resistance, obesity, and dyslipidemia. It is the consequence of an imbalance between caloric intake and energy consumption. Adiponectin protects against metabolic syndrome. Insulin-induced signaling includes activation of PI3 kinase and protein kinase B (PKB)/Akt. PKB/Akt in turn inactivates glycogen synthase kinase (GSK) 3, a major regulator of metabolism. Here, we studied the significance of PI3K-dependent GSK3 inactivation for adiponectin formation in diet-induced metabolic syndrome. Mice expressing PI3K-insensitive GSK3 (gsk3(KI)) and wild-type mice (gsk3(WT)) were fed a high-fat diet. Compared with gsk3(WT) mice, gsk3(KI) mice were protected against the development of metabolic syndrome as evident from a markedly lower weight gain, lower total body and liver fat accumulation, better glucose tolerance, stronger hepatic insulin-dependent PKB/Akt phosphorylation, lower serum insulin, cholesterol, and triglyceride levels, as well as higher energy expenditure. Serum adiponectin concentration and the activity of transcription factor C/EBPα controlling the expression of adiponectin in adipose tissue was significantly higher in gsk3(KI) mice than in gsk3(WT) mice. Treatment with GSK3 inhibitor lithium significantly decreased the serum adiponectin concentration of gsk3(KI) mice and abrogated the difference in C/EBPα activity between the genotypes. Taken together, our data demonstrate that the expression of PI3K-insensitive GSK3 stimulates the production of adiponectin and protects from diet-induced metabolic syndrome.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
animal structures
Adipose tissue
Mice, Transgenic
macromolecular substances
Insulin Resistance
Leptin
Obesity
Triglycerides
030204 cardiovascular system & hematology
Biology
Diet, High-Fat
03 medical and health sciences
chemistry.chemical_compound
Glycogen Synthase Kinase 3
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Insulin resistance
GSK-3
Internal medicine
Glucose Intolerance
medicine
Animals
Protein kinase B
PI3K/AKT/mTOR pathway
Metabolic Syndrome
Multidisciplinary
Triglyceride
Adiponectin
PTEN Phosphohydrolase
Biological Sciences
medicine.disease
030104 developmental biology
Endocrinology
chemistry
Adipose Tissue
Liver
CCAAT-Enhancer-Binding Proteins
Metabolic syndrome
Subjects
Details
- Language :
- German
- Database :
- OpenAIRE
- Journal :
- Proc. Natl. Acad. Sci. U.S.A. 113, 5754-5759 (2016)
- Accession number :
- edsair.doi.dedup.....e7cebe6d852010925b3f50cc763ba5f3