title: 13-cis-Retinoic acid therapy induces insulin resistance, regulates inflammatory parameters, and paradoxically increases serum adiponectin concentration.
abstract: 13-cis-Retinoic acid treatment causes insulin resistance and disturbances in lipid and glucose metabolism. We studied how 13-cis-retinoic acid affects inflammatory factors and adiponectin. A total of 23 healthy patients (age, 24.9 +/- 0.9 years; body mass index, 22.6 +/- 0.7 kg/m(2)) who received 13-cis-retinoic acid treatment of acne participated in the study. The patients were studied before the treatment, after 3 months of therapy, and 1 month after the treatment. Inflammatory parameters were measured, and a 4-hour oral glucose tolerance test was performed at each visit. Treatment with 13-cis-retinoic acid resulted in a significantly elevated serum adiponectin concentration (from 24.9 +/- 2.5 to 29.4 +/- 3.6 mg/L, P < .05), hemoglobin A(1c) (from 5.27% +/- 0.05% to 5.42% +/- 0.06%, P < .01), C-peptide area under the curve (from 314.2 +/- 16.6 to 350.0 +/- 21.0 (nmol . min)/L, P < .05), and triglycerides (from 0.97 +/- 0.06 to 1.29 +/- 0.10 mmol/L, P < .05), whereas high-density lipoprotein cholesterol decreased (from 1.50 +/- 0.07 to 1.38 +/- 0.08 mmol/L, P < .05). The increase in adiponectin during 13-cis-retinoic acid therapy correlated with baseline triglycerides (r = 0.51, P < .02). Many inflammatory markers, which were nonsignificantly elevated during therapy, decreased significantly after cessation of treatment. These were C-reactive protein (median from 1.78 to 1.23 mg/L, P < .05), soluble intercellular adhesion molecule 1 (from 210 +/- 10 to 204 +/- 10 microg/L, P < .02), ceruloplasmin (256 +/- 17 to 231 +/- 17 microg/L, P < .02), and erythrocyte sedimentation rate (from 6.4 +/- 1.3 to 4.7 +/- 0.9 mm/h, P < .02). Interleukin 6 concentration was unaffected by the therapy, but decreased significantly after the treatment (from 2.18 +/- 0.46 to 1.65 +/- 0.43 ng/L, P < .05). In conclusion, although treatment with 13-cis-retinoic acid results in disturbances in glucose and lipid metabolism, paradoxically serum adiponectin concentration increases. 13-cis-Retinoic acid has profound effects on the regulation of inflammatory markers.
authors.affiliation: Division of Geriatrics, Department of Medicine, Helsinki University Central Hospital, FIN-00029 HYKS Helsinki, Finland. maikki.heliovaara@hus.fi <maikki.heliovaara@hus.fi>
authors.forename: Maikki K
authors.initials: MK
authors.lastname: Heliövaara
authors.forename: Anita
authors.initials: A
authors.lastname: Remitz
authors.forename: Sakari
authors.initials: S
authors.lastname: Reitamo
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Teppo
authors.forename: Sirkka-Liisa
authors.initials: SL
authors.lastname: Karonen
authors.forename: Pertti
authors.initials: P
authors.lastname: Ebeling
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D019540:Area Under Curve; D002097:C-Reactive Protein / Q000032:analysis; D003176:Complement C3 / Q000032:analysis; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D015474:Isotretinoin / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D009961:Orosomucoid / Q000032:analysis; D000685:Serum Amyloid A Protein / Q000032:analysis
chemical_list: D052242:Adiponectin; D003176:Complement C3; D015850:Interleukin-6; D008055:Lipids; D009961:Orosomucoid; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D015474:Isotretinoin