cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids.
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.
Madsen
Lise
L
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark. lise.madsen@bmb.sdu.dk
Pedersen
Lone Møller
LM
Liaset
Bjørn
B
Ma
Tao
T
Petersen
Rasmus Koefoed
RK
van den Berg
Sjoerd
S
Pan
Jie
J
Müller-Decker
Karin
K
Dülsner
Erik D
ED
Kleemann
Robert
R
Kooistra
Teake
T
Døskeland
Stein Ove
SO
Kristiansen
Karsten
K
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
D002241:Carbohydrates; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D014508:Urea; D000242:Cyclic AMP