Increased adiposity in the retinol saturase-knockout mouse.
The enzyme retinol saturase (RetSat) catalyzes the saturation of all-trans-retinol to produce (R)-all-trans-13,14-dihydroretinol. As a peroxisome proliferator-activated receptor (PPAR) gamma target, RetSat was shown to be required for adipocyte differentiation in the 3T3-L1 cell culture model. To understand the mechanism involved in this putative proadipogenic effect of RetSat, we studied the consequences of ablating RetSat expression on retinoid metabolism and adipose tissue differentiation in RetSat-null mice. Here, we report that RetSat-null mice have normal levels of retinol and retinyl palmitate in liver, serum, and adipose tissue, but, in contrast to wild-type mice, are deficient in the production of all-trans-13,14-dihydroretinol from dietary vitamin A. Despite accumulating more fat, RetSat-null mice maintained on either low-fat or high-fat diets gain weight and have similar rates of food intake as age- and gender-matched wild-type control littermates. This increased adiposity of RetSat-null mice is associated with up-regulation of PPARgamma, a key transcriptional regulator of adipogenesis, and also its downstream target, fatty acid-binding protein 4 (FABP4/aP2). On the basis of these results, we propose that dihydroretinoids produced by RetSat control physiological processes that influence PPARgamma activity and regulate lipid accumulation in mice.-Moise, A. R., Lobo, G. P., Erokwu, B., Wilson, D. L., Peck, D., Alvarez, S., Domínguez, M., Alvarez, R., Flask, C. A., de Lera, A. R., von Lintig, J., Palczewski, K. Increased adiposity in the retinol saturase-knockout mouse.
Moise
Alexander R
AR
Department of Pharmacology, University of Kansas, Lawrence, KS, USA. alexmoise@ku.edu
Lobo
Glenn P
GP
Erokwu
Bernadette
B
Wilson
David L
DL
Peck
David
D
Alvarez
Susana
S
Domínguez
Marta
M
Alvarez
Rosana
R
Flask
Chris A
CA
de Lera
Angel R
AR
von Lintig
Johannes
J
Palczewski
Krzysztof
K
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000201:enzymology*; D050154:Adiposity / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D018752:Diet, Fat-Restricted; D004224:Diterpenes; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D000084562:Retinyl Esters; D015854:Up-Regulation / Q000502:physiology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain / Q000502:physiology
C518301:13,14-dihydroretinol; D004224:Diterpenes; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D044925:Oxidoreductases Acting on CH-CH Group Donors; C531869:retinol saturase (all trans retinol 13,14 reductase), mouse