retinol-palmitate and Weight-Gain

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.

Topics: 3T3-L1 Cells; Adipose Tissue; Adiposity; Animals; Cell Differentiation; Diet, Fat-Restricted; Diterpenes; Fatty Acid-Binding Proteins; Female; Liver; Male; Mice; Mice, Knockout; Models, Biological; Oxidoreductases Acting on CH-CH Group Donors; PPAR gamma; Retinyl Esters; Up-Regulation; Vitamin A; Weight Gain

Induction of protein expression in a tissue-specific manner by gene transfer over-expression techniques has been one means to define the function of a protein in a biological paradigm. Studies with retinoid reporter constructs transfected in mammary cell lines suggests that lactoferrin (Lf) affects retinoid signaling pathways and alters apoptosis. We tested the effects and interactions of over-expressed mammary-specific human lactoferrin (hLf) and dietary retinol palmitate on lactation and mammary gland development in mice. Increased retinol palmitate in the diet increased daily retinol equivalents (RE) to 2.6-fold over the normal mouse control diet. Transgene (Tg) expression in the dam fed control diet depressed pup weight gain. Severe depression of pup weight gain was observed when homozygote TgTg dams were fed the RE diet. Normal weight gain was restored when pups were placed with a wild type dam fed the RE diet; conversely, normal growing pups from the wild type dams showed declining weight gains when fostered to the TgTg RE-fed dams. Northern analysis of mammary tissue extracts showed a reduction in WAP and an increase in IGFBP-3 mRNA that was associated with the presence of the transgene. Histological evaluation of 3 days lactating mammary tissue showed mammary epithelial cells from TgTg animals contained excessive secretory products, suggesting a block in cellular secretion mechanisms. In addition, the mammary cells displayed a cellular apical membrane puckering that extended into the alveoli lumens. These studies demonstrate an in vivo interaction of Tg-hLf expression and dietary retinoids in mouse mammary glands. While normal mammary gland physiology may not be representative by these experiments because high Lf concentrations during early lactation are abnormal, the demonstrated biological interaction suggests that typical periods of high Lf concentrations may have impact upon developing and involuting mammary glands.

Topics: Animals; Animals, Newborn; Blotting, Northern; Blotting, Southern; Diet; Diterpenes; Female; Humans; Lactation; Lactoferrin; Mammary Glands, Animal; Mice; Mice, Transgenic; Organogenesis; Polymerase Chain Reaction; Retinyl Esters; Signal Transduction; Transgenes; Vitamin A; Weight Gain

The vitamin A (VA) value of carotenoids from fruits and vegetables is affected by many factors. This study determined the VA value of alpha-carotene isolated from carrots compared with beta-carotene and retinyl acetate supplements fed to Mongolian gerbils (Meriones unguiculatus). Gerbils (n = 38) were fed a VA-free diet for 4 wk. At baseline, 6 gerbils were killed to determine liver VA. Gerbils were divided into 3 treatment groups (n = 9/group) and given 35, 35, or 17.5 nmol retinyl acetate, alpha-carotene or beta-carotene, respectively, in 2 divided doses 5 h apart each day. The remaining 5 gerbils received oil vehicle. Gerbils were killed after 3 wk of supplementation. Serum samples and livers were collected and analyzed for VA. Liver extracts were subsequently saponified to quantify alpha-retinol. Serum retinol concentrations did not differ among the groups. Liver retinyl palmitate concentrations were significantly higher in the retinyl acetate treatment group (0.198 +/- 0.051 micromol/g; P < 0.05) than in all other groups. The alpha- and beta-carotene treatments resulted in similar retinyl palmitate concentrations, i.e., 0.110 +/- 0.026 and 0.109 +/- 0.051 micromol/g, respectively, which did not differ from the concentrations in gerbils killed at baseline (0.123 +/- 0.024 micromol/g). The oil group had significantly less retinyl palmitate (0.061 +/- 0.029 micromol/g; P < 0.05) than all other groups. alpha-Retinol was detected in livers of the alpha-carotene group (0.062 +/- 0.013 micromol/g). Thus, twice the amount of purified alpha-carotene maintained VA status as well as beta-carotene in VA-depleted gerbils. Conversion factors were approximately 5.5 microg alpha-carotene or approximately 2.8 mug beta-carotene to 1 microg retinol.

Topics: Animals; beta Carotene; Carotenoids; Daucus carota; Diet; Diterpenes; Gerbillinae; Kinetics; Liver; Male; Nutritional Status; Retinyl Esters; Vitamin A; Weight Gain

We conducted an experiment for 112 d with yearling beef heifers to evaluate the effects of cottonseed meal (CSM) fed with various concentrations of vitamin E on hematological and tissue components. Heifers were assigned randomly to four treatments, with eight heifers per treatment. The treatments consisted of the following dietary supplements: 1) CON, based on soybean meal with 30 IU vitamin E/kg; 2) GOS, based on CSM with 30 IU vitamin E/kg; 3) G+2E, based on CSM with 2,000 IU vitamin E x animal(-1) x d(-1); and 4) G+4E, based on CSM with 4,000 IU vitamin E x animal(-1) x d(-1). Supplements based on CSM provided 4.5 g of free and 50.5 g of total gossypol x animal(-1) x d(-1). The total gossypol present in the supplements was 29.1% of the negative isomer (-) and 70.9% of the positive isomer (+). Blood samples were collected at the start of the experiment and every 2 wk thereafter up to 16 wk. There was a time x treatment interaction (P<.01) for plasma alpha-tocopherol ( alpha-T) concentration; however, feeding gossypol did not decrease plasma alpha-T. Weight gain, retinol palmitate, retinol, beta-carotene (beta-C), hemoglobin, and hematocrit were not affected by treatment. Erythrocyte osmotic fragility (EOF) increased (P<.05) in gossypol-fed animals; however, vitamin E supplementation lowered EOF (P<.05). Heifers fed the supplements GOS, G+2E, and G+4E had greater (P<.01) plasma (-)-, (+)-, and total gossypol than heifers fed CON from Collection 2 to the end of the experiment. There was a treatment effect (P<.05) on vitamin E and gossypol concentrations in different tissues, with no effect (P>.05) for trace minerals (Cu, Zn, Fe, and Se). Vitamin E concentration in tissue increased with increased dietary supplementation of vitamin E. In heart and neck muscle, (-)-gossypol was greater (P<.05) than (+)-gossypol, but the reverse was true for liver. Gossypol decreased in vitro lipid peroxidation of liver homogenate in tissues. Gossypol deposition in tissue was liver > heart > muscle. In summary, gossypol from CSM did not decrease concentrations of antioxidant vitamins, including alpha-T, vitamin A, and beta-C, or have any detrimental effect on performance of beef heifers.

Topics: Alkaline Phosphatase; Animal Feed; Animals; beta Carotene; Cattle; Cottonseed Oil; Creatine Kinase; Dietary Supplements; Diterpenes; Female; Gossypol; Hematocrit; Hemoglobins; Liver; Myocardium; Neck Muscles; Osmotic Fragility; Random Allocation; Retinoids; Retinyl Esters; Vitamin A; Vitamin E; Weight Gain