Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia.
Int J Biochem Cell Biol. 2010 Jun;42(6):785-8. doi: 10.1016/j.biocel.2009.12.021. Epub 2010 Jan 4.
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.
脂联素是一种脂肪细胞因子（adipocyte-derived hormone），具有多种有益作用。它以低分子量 (LMW) 和高分子量 (HMW) 多聚体的形式分泌到循环中，后者的代谢活性更高。脂联素的高效多聚化和分泌需要广泛的翻译后修饰（PTMs）。最近的研究确定了新的 PTMs，这些 PTMs有助于脂联素的产生和清除。巯基介导的脂联素在通过内质网运输时的保留是通过与包括 ERp44 和 DsbA-L 在内的伴侣蛋白的直接相互作用发生的，这有助于多聚化和分泌。有趣的是，这似乎与脂联素的琥珀酰化直接竞争。脂联素还受到 O-糖基化/唾液酸化的影响，这会影响其从循环中的清除。与大多数脂肪细胞因子不同，脂联素水平降低，特别是 HMW，会导致与肥胖相关的疾病（如 2 型糖尿病和心血管疾病）的发病机制。调节脂联素翻译后修饰过程的策略代表了有吸引力的治疗方法。
