title: Short term 13-cis-retinoic acid treatment at therapeutic doses elevates expression of leptin, GLUT4, PPARgamma and aP2 in rat adipose tissue.
abstract: Temporary defects in the plasma lipid and glucose homeostasis are frequent complication accompanying chronic treatment with 13-cis-retinoic acid (13cRA). White adipose tissue acts as an endocrine organ producing a variety of hormones (adipocytokines) including leptin, adiponectin, tumor-necrosis factor alpha (TNFalpha) and angiotensin II (Ang II), which influence lipid metabolism, systemic insulin sensitivity and inflammation. To study the effect of a short-term 13cRA administration on metabolism of epididymal fat tissue, we treated Wistar rats with five identical therapeutic doses of 13cRA (0.8 mg/kg b.w.) by gavage during a period of 10 days. Expression of adiponectin, leptin, TNFalpha and selected proteins such as adipocyte fatty acid binding protein (aP2), insulin-dependent glucose transporter GLUT4, peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoid X receptors (RXRs) was investigated using RT-PCR. Short-term treatment with therapeutic doses of 13cRA caused significant increase of the aP2, PPARgamma and moderately RXRalpha gene expression. Similarly, the relative amount of mRNA for leptin and GLUT4 was increased, while the TNFa transcript was decreased after treatment with 13cRA. The gene expression and plasma concentration of adiponectin were without any significant changes. Since local adipose renin-angiotensin system (RAS) has been presumed to be involved in the regulation of fat tissue metabolism, we also investigated the gene expression of RAS components in epididymal fat depot. Our data has shown that 13cRA elevated Ang II receptor type 1 (AT(1) receptor)--at both, mRNA and protein level. Thus, our results demonstrate that short-term 13cRA treatment is inducing alterations in fat tissue metabolism in relation to stimulated adipogenesis.
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: K
authors.initials: K
authors.lastname: Krskova-Tybitanclova
authors.forename: D
authors.initials: D
authors.lastname: Macejova
authors.forename: J
authors.initials: J
authors.lastname: Brtko
authors.forename: M
authors.initials: M
authors.lastname: Baculikova
authors.forename: O
authors.initials: O
authors.lastname: Krizanova
authors.forename: S
authors.initials: S
authors.lastname: Zorad
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003879:Dermatologic Agents / Q000633:toxicity*; D050556:Fatty Acid-Binding Proteins / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D051275:Glucose Transporter Type 4 / Q000187:drug effects / Q000235:genetics; D015474:Isotretinoin / Q000633:toxicity*; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008297:Male; D047495:PPAR gamma / Q000172:deficiency / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000235:genetics; D047488:Retinoid X Receptors / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics
chemical_list: D003879:Dermatologic Agents; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; D020738:Leptin; D047495:PPAR gamma; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D047488:Retinoid X Receptors; D014409:Tumor Necrosis Factor-alpha; D015474:Isotretinoin