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

VL - 283

SP - 7196

EP - 7205

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 11

ER -