Title
cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids
Author
TNO Kwaliteit van Leven
Madsen, L.
Pedersen, L.M.
Liaset, B.
Ma, T.
Petersen, R.K.
van den Berg, S.
Pan, J.
Müller-Decker, K.M.
Dülsner, E.D.
Kleemann, R.
Kooistra, T.
Døskeland, S.O.
Kristiansen, K.
Publication year
2008
Abstract
The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and obesity is controversial. Using in vitro cell culture models, we show that n-6 PUFAs was pro-adipogenic under conditions with base-line levels of cAMP, but anti-adipogenic when the levels of cAMP were elevated. The anti-adipogenic action of n-6 PUFAs was dependent on a cAMP-dependent protein kinase-mediated induction of cyclooxygenase expression and activity. We show that n-6 PUFAs were pro-adipogenic when combined with a high carbohydrate diet, but non-adipogenic when combined with a high protein diet in mice. The high protein diet increased the glucagon/insulin ratio, leading to elevated cAMP-dependent signaling and induction of cyclooxygenase-mediated prostaglandin synthesis. Mice fed the high protein diet had a markedly lower feed efficiency than mice fed the high carbohydrate diet. Yet, oxygen consumption and apparent heat production were similar. Mice on a high protein diet had increased hepatic expression of PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1alpha) and genes involved in energy-demanding processes like urea synthesis and gluconeogenesis. We conclude that cAMP signaling is pivotal in regulating the adipogenic effect of n-6 PUFAs and that diet-induced differences in cAMP levels may explain the ability of n-6 PUFAs to either enhance or counteract adipogenesis and obesity. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Subject
Healthy Living
Healthy for Life
Acids
Biomolecules
Carbohydrates
Cell culture
Cytology
Ecology
Fetal monitoring
Metabolism
Organic compounds
Oxygen
Urea
Adipogenesis
Cyclooxygenase
Demanding processes
Gluconeogenesis
Heat productions
Hepatic expressions
High protein diets
In vitro
Oxygen consumptions
Peroxisome proliferator- activated receptors
Polyunsaturated fatty acids
Prostaglandin synthesis
Protein kinases
Urea syntheses
Nutrition
Cyclic AMP dependent protein kinase
Glucagon
Glucose
Insulin
Omega 6 fatty acid
Peroxisome proliferator activated receptor gamma coactivator 1alpha
Prostaglandin synthase
Urea
Carbohydrate
Unsaturated fatty acid
Adipocyte
Adipogenesis
Amino acid sequence
Animal cell
Animal cell culture
Animal experiment
Animal model
Animal tissue
Carbohydrate diet
Controlled study
Energy conservation
Enzyme activity
Enzyme induction
Gluconeogenesis
In vitro study
In vivo study
Nonhuman
Prostaglandin synthesis
Protein diet
Protein expression
Signal transduction
Urea cycle
Biological model
C57BL mouse
Cell strain 3T3
Chemistry
Cytology
Genetics
Mus
3T3-L1 Cells
Adipocytes
Adipogenesis
Animals
Carbohydrates
Cyclic AMP
Fatty Acids, Omega-6
Fatty Acids, Unsaturated
Male
Mice
Mice, Inbred C57BL
Models, Biological
Obesity
Signal Transduction
Urea
To reference this document use:
http://resolver.tudelft.nl/uuid:335cb502-a6d8-4414-97b6-eca0df06cdd2
DOI
https://doi.org/10.1074/jbc.m707775200
TNO identifier
240704
ISSN
0021-9258
Source
Journal of Biological Chemistry, 283 (283), 7196-7205
Document type
article