Abstract
The endocannabinoid system (ECS) plays an important and not yet fully understood role
in hypothalamic and peripheral regulation of food intake, obesity, and metabolism.
Two frequent single nucleotide polymorphisms (snp) have been identified in members
of the ECS: the 1359 G/A variant in the cannabinoid receptor 1 (CB1) and the P129T polymorphism in fatty acid amide hydrolase (FAAH), a key degradation enzyme of endocannabinoids. -While for the 1359 G/A variant an
association has been shown only with psychiatric diseases such as drug-abusing schizophrenia,
the P129T polymorphism has recently been proved to be correlated to a higher body
mass index (BMI) in a group of black and white Americans. However, no knowledge exists
as to whether these variants affect the outcome of a low fat diet in obese subjects.
Therefore, we genotyped a group of 451 obese and dyslipidaemic participants and observed
the biometric and metabolic outcome of a 6 week low fat diet. While no significance
was seen for the 1359 G/A variant, carriers of the P129T mutation in FAAH had a significantly greater decrease in triglycerides and total cholesterol as compared
to wild type. The reason for our findings remains to be elucidated, however, a hepatic
downregulation of endocannabinoid tone may contribute to the observed outcome in studied
subjects.
References
- 1
Matsuda LA, Lolait SH, Brownstein MJ, Yound AC, Bonner TI.
Nature.
1990;
346
561-564
- 2
Cota D, Marsicano G, Tschöp M, Grübler Y, Flachskamm C, Schubert M, Auer D, Yassouridis A,
Thöne-Reineke C, Ortmann S, Tomassoni F, Cervino C, Nisoli E, Linthorst ACE, Pasquali R,
Lutz B, Stalla GK, Pagotto U.
J Clin Invest.
2003;
112
423-431
- 3
Kirkham TC, Williams CM, Fezza F, Di Marzo V.
Br J Pharmacol.
2002;
136
550-557
- 4
Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, Fezza F, Miura GI, Palmiter RD,
Sugiura T, Kunos G.
Nature.
2001;
410
822-825
- 5
Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Batkai S, Harvey-White J,
Mackie K, Offertaler L, Wang L, Kunos G.
J Clin Investig.
2005;
115
1298-1305
- 6
Matias I, Gonthier MP, Orlando P, Martiadis V, De Petrocellis L, Cervino C, Petrosino S,
Hoareau L, Festy F, Pasquali R, Roche R, Maj M, Pagotto U, Monteleone P, Di Marzo V.
JCEM.
2006;
91
3171-3180
- 7
Shook JE, Burks TF.
J Pharmacol Exp Ther.
1999;
249
444-449
- 8
Liu YL, Connoley IP, Wilson CA, Stock MJ.
Int J Obes.
2005;
29
183-187
- 9
Batkai S, Pacher P, Osei-Hyiaman D, Radaeva S, Liu J, Harvey-White J, Offertaler L,
Mackie K, Rudd A, Bukoski RD, Kunos G.
Circulation.
2004;
110
1996-2002
- 10
Perwitz N, Fasshauer M, Klein J.
Horm Metab Res.
2006;
38
356-358
- 11
Gadzicki D, Müller-Vahl KR, Stuhrmann M.
Mol Cell Probes.
1999;
13
321-323
- 12
Leroy S, Griffon N, Bourdel MC, Olie JP, Poirier MF, Krebs MO.
Am J Med Gen.
2001;
105
749-752
- 13
Sipe JC, Waalen J, Gerber A, Beuter E.
Int J Obes.
2005;
20
755-759
- 14
Sipe JC, Chiang K, Gerber AL, Beutler E, Cravatt BF.
Proc Natl Acad Sci USA.
2002;
99
8394-8399
- 15
Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rössner S.
Lancet.
2005;
365
1389-1397
- 16
Berger A, Crozier G, Bisogno T, Cavaliere P, Innis S, Di Marzo V.
Proc Natl Acad Sci USA.
2000;
97
6402-6406
Correspondence
J. Aberle
Zentrum für Innere Medizin
3. Medizinische Klinik
Universitätsklinikum
Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg
Germany
Phone: +49/40/428 03 44 49
Fax: +49/40/428 03 23 17
Email: aberle@uke.uni-hamburg.de
