The effect of cysteamine bitartrate on adiponectin multimerization in non-alcoholic fatty liver disease and healthy subjects.
OBJECTIVE
To determine the effects of cysteamine on adiponectin multimerization in sera of patients with nonalcoholic fatty liver disease (NAFLD).


METHODS
Sera from 10 children with biopsy-proven NAFLD treated with cysteamine were assayed for adiponectin multimers at baseline, after 24 weeks of treatment, and again 16 weeks after discontinuing treatment. Pretreatment sera from subjects with NAFLD and from adult controls without NAFLD controls (n = 8) were incubated in cysteamine and multimers were measured 1 hour later. A cysteamine/adiponectin multimer dose-response curve was created.


RESULTS
Following 24 weeks of cysteamine therapy, the mean percentage increase for high, medium (MMW), and low (LMW) molecular weight multimers and total adiponectin from baseline was 53% (P = .02), 19% (P = .02), 29.4% (P = .03), and 49.3% (P = .05), respectively. Levels returned to baseline at 16 weeks after stopping therapy, unlike hepatic transaminase levels which remained low. Sera from 0 week, incubated in cysteamine for 1 hour, showed a significant mean percent increase in LMW adiponectin levels and a mean percent reduction in MMW levels compared with baseline in adults with and without NAFLD.


CONCLUSIONS
Cysteamine impacts adiponectin multimerization. Long-term cysteamine therapy increases levels of all multimers, whereas, in vitro short-term exposure causes a rapid increase in LMW and reduction in MMW multimers in NAFLD and healthy controls. Cysteamine may be a potential therapeutic agent for conditions associated with insulin-resistance, oxidative stress, and depressed adiponectin levels.
Department of Pediatrics, University of California, San Diego, San Diego, CA 92103-8450, USA.
Ranjan
R
Dohil
Lauren
L
Meyer
Susanne
S
Schmeltzer
Betty L
BL
Cabrera
Joel E
JE
Lavine
Susan A
SA
Phillips
D052242:Adiponectin / Q000097:blood / Q000737:chemistry*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D003543:Cysteamine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D005234:Fatty Liver; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease; D055503:Protein Multimerization / Q000187:drug effects*
D052242:Adiponectin; D000975:Antioxidants; D003543:Cysteamine