title: cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids.
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.
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark. lise.madsen@bmb.sdu.dk
authors: Lise
authors: L
authors: Madsen
authors: Lone Møller
authors: LM
authors: Pedersen
authors: Bjørn
authors: B
authors: Liaset
authors: Tao
authors: T
authors: Ma
authors: Rasmus Koefoed
authors: RK
authors: Petersen
authors: Sjoerd
authors: S
authors: van den Berg
authors: Jie
authors: J
authors: Pan
authors: Karin
authors: K
authors: Müller-Decker
authors: Erik D
authors: ED
authors: Dülsner
authors: Robert
authors: R
authors: Kleemann
authors: Teake
authors: T
authors: Kooistra
authors: Stein Ove
authors: SO
authors: Døskeland
authors: Karsten
authors: K
authors: Kristiansen
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D000818:Animals; D002241:Carbohydrates / Q000737:chemistry; D000242:Cyclic AMP / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009765:Obesity / Q000235:genetics*; D015398:Signal Transduction; D014508:Urea / Q000378:metabolism
chemical_list: D002241:Carbohydrates; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D014508:Urea; D000242:Cyclic AMP