Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid

Abstract

Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under investigation for its anticancer effects as is the isomer, all-trans-retinoic acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n=24/sex/dose), or soy oil (n=16/sex) and blood was sampled 30-480 min after the last gavage. The body weight was unaffected; however, the liver/body weight ratios were increased by both doses of all-trans-RA. Sex differences were noted for levels of cholesterol, creatine, triglycerides, albumin, alanine aminotransferase and total protein. Both doses of all-trans-RA reduced albumin levels to approximately 90% of the control and total protein levels to approximately 93% of the control while substantially elevating triglyceride levels to approximately 66%-99% above the control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group were approximately 62% higher than the controls and total protein levels were approximately 5% less. Glucose levels were affected by sex and RA treatment in that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA had lower (13%-19%) levels than the same-sex controls; however, females were not similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin or adiponectin. On a mg kg(-1) basis, all-trans-RA was more potent than 13-cis-RA. These results replicate previous findings of RA-induced increased triglyceride levels. Additionally, several new findings indicate there may be sex-specific effects of RA treatment. Finally, neither treatment appeared to alter the typical diurnal cycles of these endpoints.

Lipophilic Micronutrients and Adipose Tissue Biology

“…Vitamin A supplementation in the diet of genetically obese WNIN/Ob rats resulted in a decreased total body weight related to a decrease in adiposity and lowered glycemia and insulinemia [65,66]. Interestingly, similar results were reported using either all- trans or 13- cis RA [67]. Sakamuri et al attributed this anti-obesity effect to the ability of vitamin A to decrease the activity of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme involved in the synthesis of glucocorticoids [68], hormones that have been shown to promote pre-adipocyte differentiation [69].…”

Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients

“…Although it is an effective therapy for acne, isotretinoin is associated with significant adverse effects, including cheilitis, dry skin and mucous membranes [22], epistaxis, increased risk of cutaneous Staphylococcus aureus infections [23], myalgias, and pseudotumor cerebri [24]. Frequently reported blood chemistry abnormalities in isotretinoin users include elevated levels of triglycerides and cholesterol [25], elevated LDL concentrations and decreased HDL concentrations [26]. In our current study, isotretinoin treatment often caused significant elevations in cholesterol, LDL-C, and triglycerides, which are comparable with results seen in the literature.…”

Dietary regulation of adiponectin by direct and indirect lipid activators of nuclear hormone receptors

“…Only scarce results on the effect of metabolites of vitamin A and notably retinoic acid were reported [63,64]. Zhang et al observed a decrease of adiponectin mRNA levels in white adipose tissue of mice treated with a single dose of all-trans retinoic acid [65], whereas comparable treatment had no effect on adiponectin plasma concentration in rats [66]. The downregulatory effect of all-trans retinoic acid on adiponectin expression was also confirmed in 3T3-L1 adipocytes [25,67].…”