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cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids

Author: Madsen, L. · Pedersen, L.M. · Liaset, B. · Ma, T. · Petersen, R.K. · Berg, S. van den · Pan, J. · Müller-Decker, K.M. · Dülsner, E.D. · Kleemann, R. · Kooistra, T. · Døskeland, S.O. · Kristiansen, K.
Institution: TNO Kwaliteit van Leven
Source:Journal of Biological Chemistry, 11, 283, 7196-7205
Identifier: 240704
doi: doi:10.1074/jbc.M707775200
Keywords: 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 · Healthy for Life · Healthy Living


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-1α (peroxisome proliferator-activated receptor γ coactivator 1α) 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.