cAMP-depending signaling regulates the adipogenic effect of N-6 polyunsaturated fatty acids

Lise Madsen, Lone Møller Pedersen, Bjørn Liaset, Tao Ma, Rasmus Koefoed Petersen, Sjoerd van den Berg, Jie Pan, Karin Müller-Decker, Erik D Dülsner, Robert Kleemann, Teake Kooistra, Stein Ove Døskeland, Karsten Kristiansen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and obesity is controversial as fundamentally opposing results both in vivo and in vitro have been reported. Using in vitro cell culture models we show that the adipogenic action of the n-6 PUFA arachidonic acid was dependent on the intracellular levels of cAMP. In conditions with baseline intracellular levels of cAMP, n-6 PUFAs acted pro-adipogenic, whereas n-6 PUFAs acted anti-adipogenic when the intracellular levels of cAMP were elevated. The anti-adipogenic action of n-6 PUFAs was dependent on a PKA-mediated induction of cyclooxygenase (COX) expression and activity. In vivo the intracellular levels of cAMP are modulated in response to dietary intake of different classes of macronutrients. Accordingly, 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 COX-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-1a 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 can explain the ability of n-6 PUFAs to either enhance or counteract adipogenesis and obesity.
OriginalsprogEngelsk
TidsskriftJournal of Biological Chemistry
Vol/bind283
Udgave nummer11
Sider (fra-til)7196-7205
ISSN0021-9258
DOI
StatusUdgivet - 2008

Citer dette

Madsen, L., Pedersen, L. M., Liaset, B., Ma, T., Petersen, R. K., van den Berg, S., ... Kristiansen, K. (2008). cAMP-depending signaling regulates the adipogenic effect of N-6 polyunsaturated fatty acids. Journal of Biological Chemistry, 283(11), 7196-7205. https://doi.org/10.1074/jbc.M707775200
Madsen, Lise ; Pedersen, Lone Møller ; Liaset, Bjørn ; Ma, Tao ; Petersen, Rasmus Koefoed ; van den Berg, Sjoerd ; Pan, Jie ; Müller-Decker, Karin ; Dülsner, Erik D ; Kleemann, Robert ; Kooistra, Teake ; Døskeland, Stein Ove ; Kristiansen, Karsten. / cAMP-depending signaling regulates the adipogenic effect of N-6 polyunsaturated fatty acids. I: Journal of Biological Chemistry. 2008 ; Bind 283, Nr. 11. s. 7196-7205.
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title = "cAMP-depending 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 as fundamentally opposing results both in vivo and in vitro have been reported. Using in vitro cell culture models we show that the adipogenic action of the n-6 PUFA arachidonic acid was dependent on the intracellular levels of cAMP. In conditions with baseline intracellular levels of cAMP, n-6 PUFAs acted pro-adipogenic, whereas n-6 PUFAs acted anti-adipogenic when the intracellular levels of cAMP were elevated. The anti-adipogenic action of n-6 PUFAs was dependent on a PKA-mediated induction of cyclooxygenase (COX) expression and activity. In vivo the intracellular levels of cAMP are modulated in response to dietary intake of different classes of macronutrients. Accordingly, 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 COX-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-1a 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 can explain the ability of n-6 PUFAs to either enhance or counteract adipogenesis and obesity.",
author = "Lise Madsen and Pedersen, {Lone M{\o}ller} and Bj{\o}rn Liaset and Tao Ma and Petersen, {Rasmus Koefoed} and {van den Berg}, Sjoerd and Jie Pan and Karin M{\"u}ller-Decker and D{\"u}lsner, {Erik D} and Robert Kleemann and Teake Kooistra and D{\o}skeland, {Stein Ove} and Karsten Kristiansen",
year = "2008",
doi = "10.1074/jbc.M707775200",
language = "English",
volume = "283",
pages = "7196--7205",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
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Madsen, L, Pedersen, LM, Liaset, B, Ma, T, Petersen, RK, van den Berg, S, Pan, J, Müller-Decker, K, Dülsner, ED, Kleemann, R, Kooistra, T, Døskeland, SO & Kristiansen, K 2008, 'cAMP-depending signaling regulates the adipogenic effect of N-6 polyunsaturated fatty acids', Journal of Biological Chemistry, bind 283, nr. 11, s. 7196-7205. https://doi.org/10.1074/jbc.M707775200

cAMP-depending signaling regulates the adipogenic effect of N-6 polyunsaturated fatty acids. / Madsen, Lise; Pedersen, Lone Møller; Liaset, Bjørn; Ma, Tao; Petersen, Rasmus Koefoed; van den Berg, Sjoerd; Pan, Jie; Müller-Decker, Karin; Dülsner, Erik D; Kleemann, Robert; Kooistra, Teake; Døskeland, Stein Ove; Kristiansen, Karsten.

I: Journal of Biological Chemistry, Bind 283, Nr. 11, 2008, s. 7196-7205.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - cAMP-depending 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

PY - 2008

Y1 - 2008

N2 - The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and obesity is controversial as fundamentally opposing results both in vivo and in vitro have been reported. Using in vitro cell culture models we show that the adipogenic action of the n-6 PUFA arachidonic acid was dependent on the intracellular levels of cAMP. In conditions with baseline intracellular levels of cAMP, n-6 PUFAs acted pro-adipogenic, whereas n-6 PUFAs acted anti-adipogenic when the intracellular levels of cAMP were elevated. The anti-adipogenic action of n-6 PUFAs was dependent on a PKA-mediated induction of cyclooxygenase (COX) expression and activity. In vivo the intracellular levels of cAMP are modulated in response to dietary intake of different classes of macronutrients. Accordingly, 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 COX-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-1a 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 can 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 as fundamentally opposing results both in vivo and in vitro have been reported. Using in vitro cell culture models we show that the adipogenic action of the n-6 PUFA arachidonic acid was dependent on the intracellular levels of cAMP. In conditions with baseline intracellular levels of cAMP, n-6 PUFAs acted pro-adipogenic, whereas n-6 PUFAs acted anti-adipogenic when the intracellular levels of cAMP were elevated. The anti-adipogenic action of n-6 PUFAs was dependent on a PKA-mediated induction of cyclooxygenase (COX) expression and activity. In vivo the intracellular levels of cAMP are modulated in response to dietary intake of different classes of macronutrients. Accordingly, 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 COX-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-1a 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 can 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

VL - 283

SP - 7196

EP - 7205

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 11

ER -