Fatty acid desaturation and the regulation of adiposity in Caenorhabditis elegans

被引:183
作者
Brock, Trisha J. [1 ]
Browse, John [1 ]
Watts, Jennifer L. [1 ]
机构
[1] Washington State Univ, Inst Biol Chem, Pullman, WA 99164 USA
关键词
D O I
10.1534/genetics.107.071860
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Monounsaturated fatty acids are essential components of membrane and storage lipids. Their synthesis depends on the conversion of saturated fatty acids to unsaturated fatty acids by Delta 9 desaturases. Caenorhabditis elegans has three Delta 9 desaturases encoded by the genes fat-5, fat-6, and fat-7. We generated nematodes that display a range of altered fatty acid compositions by constructing clouble-mutant strains that combine mutations in fat-5, fat-6, and fat-7. All three double-mutant combinations have reduced survival at low temperatures. The fat-5;fat-6 double mutants display relatively subtle fatty acid composition alterations under standard conditions, but extreme fatty acid composition changes and reduced survival in the absence of food. The strain with the most severe defect in the production of unsaturated fatty acids, fat-6,fat-7, exhibits slow growth and reduced fertility. Strikingly, the fat-6,fat-7 double-mutant animals have decreased fat stores and increased expression of genes involved in fatty acid oxidation. We conclude that the Delta 9 desaturases, in addition to synthesizing unsaturated Fatty acids for properly functioning membranes, play key roles in lipid partitioning and in the regulation of fat storage.
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收藏
页码:865 / 875
页数:11
相关论文
共 47 条
[1]  
[Anonymous], 1988, NEMATODE CAENORHABDI
[2]   Cell nonautonomy of C-elegans daf-2 function in the regulation of diapause and life span [J].
Apfeld, J ;
Kenyon, C .
CELL, 1998, 95 (02) :199-210
[3]   Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes [J].
Ashrafi, K ;
Chang, FY ;
Watts, JL ;
Fraser, AG ;
Kamath, RS ;
Ahringer, J ;
Ruvkun, G .
NATURE, 2003, 421 (6920) :268-272
[4]   Diet, cancer, and the lipidome [J].
Bougnoux, P ;
Giraudeau, B ;
Couet, C .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2006, 15 (03) :416-421
[5]   Genetic regulation of unsaturated fatty acid composition in C-elegans [J].
Brock, Trisha J. ;
Browse, John ;
Watts, Jennifer L. .
PLOS GENETICS, 2006, 2 (07) :997-1005
[6]  
Choi JY, 1996, J BIOL CHEM, V271, P3581
[7]   Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss [J].
Cohen, P ;
Miyazaki, M ;
Socci, ND ;
Hagge-Greenberg, A ;
Liedtke, W ;
Soukas, AA ;
Sharma, R ;
Hudgins, LC ;
Ntambi, JM ;
Friedman, JM .
SCIENCE, 2002, 297 (5579) :240-243
[8]   Caenorhabditis elegans p53:: Role in apoptosis, meiosis, and stress resistance [J].
Derry, WB ;
Putzke, AP ;
Rothman, JH .
SCIENCE, 2001, 294 (5542) :591-595
[9]   The role of stearoyl-CoA desaturase in the control of metabolism [J].
Dobrzyn, A ;
Ntambi, JM .
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, 2005, 73 (01) :35-41
[10]   Stearoyl-CoA desaturase as a new drug target for obesity treatment [J].
Dobrzyn, A ;
Ntambi, JM .
OBESITY REVIEWS, 2005, 6 (02) :169-174