TY - JOUR
T1 - Increased adiposity in the retinol saturase-knockout mouse
AU - Moise, Alexander R.
AU - Lobo, Glenn P.
AU - Erokwu, Bernadette
AU - Wilson, David L.
AU - Peck, David
AU - Alvarez, Susana
AU - Domínguez, Marta
AU - Alvarez, Rosana
AU - Flask, Chris A.
AU - De Lera, Angel R.
AU - Von Lintig, Johannes
AU - Palczewski, Krzysztof
PY - 2010/4
Y1 - 2010/4
N2 - 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) γ 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 PPARγ, 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 PPARγ 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.
AB - 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) γ 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 PPARγ, 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 PPARγ 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.
KW - Dihydroretinol
KW - Retinoic acid
KW - Retinoic acid receptor
KW - Retinol-binding proteins
UR - http://www.scopus.com/inward/record.url?scp=77951644959&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951644959&partnerID=8YFLogxK
U2 - 10.1096/fj.09-147207
DO - 10.1096/fj.09-147207
M3 - Article
C2 - 19940255
AN - SCOPUS:77951644959
SN - 0892-6638
VL - 24
SP - 1261
EP - 1270
JO - FASEB Journal
JF - FASEB Journal
IS - 4
ER -