TY - JOUR
T1 - cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids
AU - Madsen, Lise
AU - Pedersen, Lone Møller
AU - Liaset, Bjørn
AU - Ma, Tao
AU - Petersen, Rasmus Koefoed
AU - van den Berg, Sjoerd
AU - Pan, Jie
AU - Müller-Decker, Karin
AU - Dülsner, Erik D
AU - Kleemann, Robert
AU - Kooistra, Teake
AU - Døskeland, Stein Ove
AU - Kristiansen, Karsten
N1 - Keywords: 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
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
U2 - 10.1074/jbc.M707775200
DO - 10.1074/jbc.M707775200
M3 - Journal article
C2 - 18070879
SN - 0021-9258
VL - 283
SP - 7196
EP - 7205
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 11
ER -
