Adiponectin--it's all about the modifications.
Adiponectin is an adipokine (adipocyte-derived hormone) with multiple salutary effects. It is secreted into the circulation as low molecular weight (LMW) and high molecular weight (HMW) multimers with the latter being more metabolically active. Extensive post-translational modifications (PTMs) are required for efficient adiponectin multimerisation and secretion. Recent studies have identified novel PTMs that contribute to the efficacy of adiponectin production and clearance. Thiol-mediated retention of adiponectin occurs during transit through the ER, via direct interactions with chaperones including ERp44 and DsbA-L, and facilitates multimerisation and secretion. Interestingly, this appears to be in direct competition with adiponectin succination. Adiponectin is also subject to O-glycosylation/sialylation which affects clearance from the circulation. In contrast to most adipokines, reduced adiponectin levels, particularly HMW, contribute to the aetiology of obesity-related diseases such as type 2 diabetes and cardiovascular disease. Strategies that modulate processes governing PTM of adiponectin represent attractive therapeutic approaches.
Simpson
Fiona
F
Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia.
Whitehead
Jonathan P
JP
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D047495:PPAR gamma / Q000819:agonists; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
D052242:Adiponectin; D047495:PPAR gamma; D011994:Recombinant Proteins; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione