tretinoin and Hyperlipidemias

Topics: Abnormalities, Drug-Induced; Adult; Alitretinoin; Anti-Inflammatory Agents; Capsules; Clinical Trials as Topic; Contraception; Contraindications; Drug Administration Routes; Drug Costs; Eczema; Female; France; Headache; Humans; Hyperlipidemias; Immunologic Factors; Male; Pregnancy; Retinoid X Receptors; Social Security; Tretinoin

Topics: Adult; Cholesterol; Coronary Disease; Etretinate; Humans; Hyperlipidemias; Isotretinoin; Lipids; Lipoproteins; Liver; Male; Tretinoin; Triglycerides

Patients with newly diagnosed acute promyelocytic leukemia (APL) are often obese or overweight, accompanied by metabolic disorders, such as dyslipidemia. However, the link between dyslipidemia and leukemia is obscure. Here, we conducted a retrospective study containing 1,412 cases (319 newly diagnosed APL patients, 393 newly diagnosed non-APL acute myeloid leukemia patients, and 700 non-tumor controls) and found that APL patients had higher triglyceride levels than non- APL and control groups. Using clinical data, we revealed that hypertriglyceridemia served as a risk factor for early death in APL patients, and there was a positive correlation between triglyceride levels and leukocyte counts. RNA sequencing analysis of APL patients having high or normal triglyceride levels highlighted the contribution of peroxisome proliferatoractivated receptor-α (PPARα), a crucial regulator of cell metabolism and a transcription factor involved in cancer development. The genome-wide chromatin occupancy of PPARα revealed that PPARα co-existed with PML/RARα within the super-enhancer regions to promote cell proliferation. PPARα knockdown affected the expression of target genes responsible for APL proliferation, including FLT3, and functionally inhibited the proliferation of APL cells. Moreover, in vivo results in mice having high fat diet-induced high triglyceride levels supported the connection between high triglyceride levels and the leukemic burden, as well as the involvement of PPARα-mediated-FLT3 activation in the proliferation of APL cells. Our findings shed light on the association between APL proliferation and high triglyceride levels and provide a genetic link to PPARα-mediated hyperlipidemia in APL.

Topics: Animals; Hyperlipidemias; Hypertriglyceridemia; Leukemia, Promyelocytic, Acute; Mice; Oncogene Proteins, Fusion; PPAR alpha; Retrospective Studies; Tretinoin; Triglycerides

The aim of this study is to evaluate the role of All-Trans Retinoic Acid, the biologically active metabolite of retinoids, on liver steatosis in a rabbit model of high fat induced lever steatosis. 30 male rabbits were evaluated in 5 groups: group 1 treated with normal diet, group 2-5 included rabbit's groups 2 to 5 were fed on high cholesterol diet, group 2 received no drugs, group 3 received atorvastatin, group 4 received atRA, and group 5 received both the drugs. the liver was obtained for histopathological evaluation. oral administration of atRA, atorvastatin or their combination significantly decreased serum levels of total cholesterol, LDL, AST and ALT. atorvastatin slightly but atRA remarkably decreased liver steatosis where the difference was significant. atRA group showed the highest TAC and the lowest PCO concentrations. atRA can be effective in reducing liver steatosis and its antioxidant effect plays a crucial role in the process.HighlightsNon-alcoholic fatty liver disease (NAFLD) is the most common disorder of the liver in general population and is strongly associated with metabolic risk factors including hyperlipidaemia, obesity and diabetes.atRA is very effective in reducing liver steatosis and its antioxidant effect plays a crucial role in the process.we suggest focussing on other aspects of liver steatosis such as carbohydrate metabolism and insulin resistance in order to find better ways of controlling and treating liver steatosis.

Topics: Animals; Antioxidants; Atorvastatin; Diet, High-Fat; Humans; Hyperlipidemias; Liver; Male; Non-alcoholic Fatty Liver Disease; Rabbits; Tretinoin

Evidence has shown that hyperlipidemia is associated with retinoid dyshomeostasis. In liver, retinol is mainly oxidized to retinal by retinol dehydrogenases (RDHs) and alcohol dehydrogenases (ADHs), further converted to retinoic acid by retinal dehydrogenases (RALDHs). The aim of this study was to investigate whether high-fat diet (HFD) induced hyperlipidemia affected activity and expression of hepatic ADHs/RDHs and RALDHs in rats. Results showed that retinol levels in liver, kidney and adipose tissue of HFD rats were significantly increased, while plasma retinol and hepatic retinal levels were markedly decreased. HFD rats exhibited significantly downregulated hepatic ADHs/RDHs activity and Adh1, Rdh10 and Dhrs9 expression. Oppositely, hepatic RALDHs activity and Raldh1 expression were upregulated in HFD rats. In HepG2 cells, treatment of HFD rat serum inhibited ADHs/RDHs activity and induced RALDHs activity. Among the tested abnormally altered components in HFD rat serum, cholesterol reduced ADHs/RDHs activity and RDH10 expression, while induced RALDHs activity and RALDH1 expression in HepG2 cells. Contrary to the effect of cholesterol, cholesterol-lowering agent pravastatin upregulated ADHs/RDHs activity and RDH10 expression, while suppressed RALDHs activity and RALDH1 expression. In conclusion, hyperlipidemia oppositely altered activity and expression of hepatic ADHs/RDHs and RALDHs, which is partially due to the elevated cholesterol levels.

Topics: Adipose Tissue; Alcohol Oxidoreductases; Animals; Cholesterol; Diet, High-Fat; Down-Regulation; Gene Expression; Hep G2 Cells; Humans; Hyperlipidemias; Kidney; Liver; Male; Oxidoreductases; Rats, Sprague-Dawley; Retina; Retinaldehyde; Retinoids; Tretinoin; Up-Regulation; Vitamin A

Chlamydia pneumoniae, a common respiratory pathogen, has been associated with cardiovascular disease. C. pneumoniae infection accelerates atherosclerotic lesion development in hyperlipidemic animals. Retinoic acid, an anti-oxidant, inhibits infection of endothelial cells by C. pneumoniae. The present study demonstrated that retinoic acid suppresses the acceleration of foam cell lesion development induced by C. pneumoniae in hyperlipidemic C57BL/6J mice. Retinoic acid treatment had no effect on foam cell lesion development in uninfected animals. Lung infection and duration was decreased in treated mice, suggesting one mechanism by which retinoic acid reduces C. pneumoniae-accelerated foam cell lesion formation in hyperlipidemic mice.

Topics: Animals; Atherosclerosis; Chlamydophila pneumoniae; Disease Models, Animal; Foam Cells; Humans; Hyperlipidemias; Lung; Male; Mice; Mice, Inbred C57BL; Pneumonia, Bacterial; Specific Pathogen-Free Organisms; Treatment Outcome; Tretinoin

Treatment with retinoids results in increased serum triglyceride and cholesterol and reduced HDL-cholesterol; dietary supplementation with fish oil lowers serum lipids. Therefore combining retinoids with fish oil may reduce retinoid hyperlipidaemia. Increased triglyceride due to isotretinoin was reduced by 70% (P less than 0.05) and cholesterol by 45% (P less than 0.05) after addition of fish oil; placebo oil had no effect. These decreases were not associated with changes in levels of HDL-cholesterol or reduction of increased levels of apoprotein B. Increased triglyceride due to etretinate was reversed after the addition of fish oil (P less than 0.01), but cholesterol levels did not change. Therefore fish oil inhibits hypertriglyceridaemia due to isotretinoin and etretinate and reduces increased cholesterol levels due to isotretinoin; this effect is likely to be due to altered lipoprotein composition.

Topics: Acne Vulgaris; Adolescent; Adult; Aged; Cholesterol; Etretinate; Female; Fish Oils; Humans; Hyperlipidemias; Isotretinoin; Male; Middle Aged; Psoriasis; Tretinoin; Triglycerides

Topics: Adult; Estrogens, Conjugated (USP); Female; Humans; Hyperlipidemias; Isotretinoin; Pancreatitis; Plasmapheresis; Tretinoin; Triglycerides

This report describes a series of experiments that attempt to characterize the lipidemia accompanying retinoic acid administration. After feeding young adult male Sprague-Dawley rats, 1.2 Retinol Equivalents (R.E.) retinyl acetate plus supplemental retinoic acid (100 microgram/g dry diet) for three days and fasting for 6-8 hr, triglyceride, cholesterol, and phospholipid content of various serum lipoprotein fractions were determined. When compared to unsupplemented controls, both the serum very low density lipoprotein (VLDL) and the high density lipoprotein (HDL) fractions of the retinoic acid-fed rats were found to harbor an elevated triglyceride content. While VLDL cholesterol and phospholipid content were also elevated, total serum cholesterol and phospholipids were not statistically altered. The detergent Triton WR-1339 was used to depress serum triglyceride clearance in order to assess the effects of retinoic acid feeding on serum triglyceride levels. Triglyceride accumulation started earlier after Triton treatment and was greater when rats were fed 100 microgram/g retinoic acid for three days prior to testing. Red and white gastrocnemius muscle, cardiac ventricular muscle, and perirenal adipose tissue were removed from rats following retinoic acid feeding. Analysis of these tissues for lipoprotein lipase (EC 3.1.1.3) activity showed a decrease in adipose tissue, a large depression in both areas of gastrocnemius muscle and no change in cardiac muscle as a result of retinoic acid feeding.

Topics: Animals; Cholesterol; Hyperlipidemias; Lipoprotein Lipase; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Phospholipids; Polyethylene Glycols; Rats; Tretinoin; Triglycerides

The effects of all-trans and 13-cis retinoic acid upon serum and liver lipids were investigated in Sprague-Dawley rats. Groups of rats were fed daily with 105, 210 and 315 micrograms/g diet of one of the retinoids for periods of up to 8 days. Other groups were injected intraperitoneally (I.P.) daily with retinoids at levels equivalent to the daily intake of rats receiving 105 or 210 micrograms of retinoid/g diet. All dietary concentrations of all-trans retinoic acid induced hypertriglyceridemia, however, only the highest dietary concentration of the 13-cis form caused this response. Injection of the all-trans form consistently increased serum triglycerides, while 13-cis retinoic acid did so in only one case. Retinoid-fed rats fasted for 6 hours before blood sampling demonstrated similar increases in serum triglycerides compared to their respective controls. Also, retinoid administration reduced serum retinol at all levels tested with the all-trans form appearing to be more potent. Growth and feed intake was somewhat reduced in rats receiving the highest level of all-trans retinoic acid. Liver analysis did not reveal fatty liver or alterations in phospholipid, cholesterol, or vitamin A content in any groups monitored. Our previous studies have shown induction of hypertriglyceridemia when rats were fed as low as 26 micrograms/g diet of all-trans retinoic acid. The current studies would indicate that feeding 315 micrograms/g diet of the 13-cis isomer was required to elicit a similar response.

Topics: Animals; Cholesterol; Dose-Response Relationship, Drug; Fasting; Hyperlipidemias; Lipid Metabolism; Lipids; Liver; Male; Rats; Stereoisomerism; Structure-Activity Relationship; Tretinoin; Triglycerides

The effects of level and feeding frequency of retinoic acid (OIC) or retinyl acetate (YL) on the accumulation of lipids in the serum and liver of rats were investigated. Male Sprague-Dawley rats were fed ad libitum 1% cholesterol diets with or without supplemental OIC or YL. Vitamin A-fed groups included (per g of dry diet): 105 microgram of OIC or 113 microgram YL daily for 28 days, 735 microgram OIC or 791 microgram YL once each week for 28 days; and 735 or 105 microgram OIC on day 1 or 105 microgram OIC daily for the week experiment. Daily feeding of OIC or YL increased serum triglyceride concentrations as compared to conrols. Several days after removal of OIC or 1 week after removal of supplemental YL from the rat diets, serum triglyceride concentrations returned to basal levels. Cholesterol feeding elevated serum cholesterol as well as hepatic cholesterol, total lipids and vitamin A concentrations. Daily OIC feeding depressed serum and hepatic cholesterol concentrations. These results show that daily supplement of vitamin A increased serum triglycerides and reduced serum and hepatic cholesterol concentrations. Serum and liver alterations were dependent on continued feeding.

Topics: Animals; Cholesterol; Cholesterol, Dietary; Diterpenes; Female; Hyperlipidemias; Lipid Metabolism; Liver; Organ Size; Phospholipids; Rats; Retinyl Esters; Tretinoin; Triglycerides; Vitamin A

Many reports have appeared in the literature suggesting that vitamin A may exert some of its effects via changes in adrenocortical activity. A series of experiments were performed in order to assess the possible role of the adrenal gland in vitamin A-induced lipid alterations in rats. Adrenalectomized, sham-operated, and intact rats were fed retinoic acid or retinyl acetate at several levels. Either 25 or 100 retinol equivalents (RE)/g dry diet were fed to male Sprague-Dawley rats for periods of 7 or 28 days. Neither compound had an effect on the concentration of liver glycerides, phospholipids, cholesterol, or total lipids. Vitamin A, especially in the form of retinoic acid, was found to induce an elevation of plasma triglycerides. The presence of the adrenal gland was not necessary for the induction of hypertriglyceridemia nor was there any indication of increased adrenocortical output (as measured by plasma corticosterone level) as a result of vitamin A feeding. There was a reduction in circulating retinol as a result of retinoic acid feeding at either 25 or 100 RE in sham-operated and adrenalectomized rats but not in unoperated rats. These experiments demonstrate that vitamin A, especially in the form of retinoic acid, fed at as low as 25 RE/g diet to the rat can induce hypertriglyceridemia, and that the adrenal gland does not mediate this effect.

Topics: Adrenal Glands; Adrenalectomy; Animals; Body Weight; Cholesterol; Corticosterone; Hyperlipidemias; Lipid Metabolism; Liver; Male; Phospholipids; Rats; Tretinoin; Triglycerides; Vitamin A