HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 11, 7196-7205, March 14, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/11/7196    most recent M707775200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Madsen, L. Articles by Kristiansen, K. PubMed PubMed Citation Articles by Madsen, L. Articles by Kristiansen, K. Social Bookmarking                      What's this?

cAMP-dependent Signaling Regulates the Adipogenic Effect of n-6 Polyunsaturated Fatty Acids^*

Lise Madsen¹, Lone Møller Pedersen, Bjørn Liaset, Tao Ma, Rasmus Koefoed Petersen, Sjoerd van den Berg^¶2, Jie Pan^||, Karin Müller-Decker^**, Erik D. Dülsner^**, Robert Kleemann³, Teake Kooistra³, Stein Ove Døskeland, and Karsten Kristiansen⁴

From the Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark, the National Institute of Nutrition and Seafood Research, 5817 Bergen, Norway, the ^¶Department of Human Genetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands, the ^||Key Laboratory of Anti-Morbid Animal Biology, College of Life Sciences, Shandong Normal University, Jinan 250014, China, the ^**Core Facility of Tumor Models, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany, the Department of Biosciences, TNO, P.O. Box 2215, 2301 CE Leiden, The Netherlands, and the Department of Biomedicine, University of Bergen, Bergen 5097, Norway

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-1 (peroxisome proliferator-activated receptor coactivator 1) 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.

Received for publication, September 17, 2007 , and in revised form, December 7, 2007.

^* This work was carried out as a part of the research program of the Danish Obesity Research Centre, which is supported by Danish Council for Strategic Research Grant 2101-06-0005. This work was also supported by the Danish Natural Science Research Council, the Norwegian Research Council, and the NOVO Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables 1-3.

² Supported by grants from the Nutrigenomics Consortium, the Center of Medical Systems Biology established by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research, and Netherlands Organization for Scientific Research Investment Grant 911-04-001.

³ Supported by European Nutrigenomics Organisation NuGO Grant CT-2004-505944 and TNO Program Personalized Health VP9.

¹ To whom correspondence may be addressed: National Institute of Nutrition and Seafood Research, Postboks 2029, 5817 Bergen, Norway. Fax: 47-55-90-52-99; E-mail: lise.madsen{at}bmb.sdu.dk.

⁴ To whom correspondence may be addressed: Dept. of Biochemistry and Molecular Biology, Campusvej 55, University of Southern Denmark, 5230 Odense M, Denmark. Fax: 45-6550-2467; E-mail: kak{at}bmb.sdu.dk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?