Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression
Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression
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DOI：
10.1007/s00125-004-1660-8
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发表时间：
2005-03-01
期刊：
影响因子：
8.2
通讯作者：
Saulnier-Blache, JS
中科院分区：
文献类型：
--
作者：
Boucher, J;Quilliot, D;Saulnier-Blache, JS
目的/假设：自分泌运动因子是一种由脂肪细胞分泌的溶血磷脂酶 D，其表达在肥胖、糖尿病 db/db 小鼠中显着上调。本研究的目的是描述脂肪细胞自分泌运动因子表达调节所涉及的病理生理学和细胞机制。方法：对 db/db 小鼠（肥胖和高度糖尿病 2 型）、金硫葡萄糖治疗（GTG）小鼠（高度肥胖和中度糖尿病 2 型）、高脂饮食喂养（HFD）小鼠（肥胖和中度糖尿病 2 型）、链脲佐菌素治疗小鼠（瘦和糖尿病 1 型）以及患有葡萄糖不耐症的严重肥胖人类的脂肪组织中的自分泌运动因子 mRNA 进行定量。结果：与非肥胖对照相比，db/db 小鼠中的自分泌运动因子表达显着增加，但 GTG、HFD 或链脲佐菌素治疗的小鼠中则没有。在db/db小鼠发育过程中，自分泌运动因子的上调发生在高胰岛素血症出现后仅3周，并且与高血糖同时出现。与非肥胖和 HFD 诱导的肥胖小鼠相比，db/db 小鼠的脂肪细胞对胰岛素刺激的葡萄糖摄取表现出更强的损害。在 3T3F442A 脂肪细胞中，用 TNF α（促进胰岛素抵抗的细胞因子）治疗可上调自分泌运动因子的表达，而用罗格列酮治疗（胰岛素增敏化合物）则可下调自分泌运动因子的表达。最后，在表现出胰岛素抵抗和糖耐量受损的患者中，脂肪组织自分泌运动因子的表达显着上调。结论/解释：本研究表明，脂肪细胞自分泌运动因子表达存在 db/db 特异性上调，这可能与严重 2 型糖尿病表型和脂肪细胞胰岛素抵抗有关，而不是与过度肥胖本身有关。它还表明，人类 2 型糖尿病也与脂肪细胞自分泌运动因子表达的上调有关。
Aims/hypothesis: Autotaxin is a lysophospholipase D that is secreted by adipocytes and whose expression is substantially up-regulated in obese, diabetic db/db mice. The aim of the present study was to depict the physiopathological and cellular mechanisms involved in regulation of adipocyte autotaxin expression. Methods: Autotaxin mRNAs were quantified in adipose tissue from db/db mice (obese and highly diabetic type 2), gold-thioglucose-treated (GTG) mice (highly obese and moderately diabetic type 2), high-fat diet-fed (HFD) mice (obese and moderately diabetic type 2), streptozotocin-treated mice (thin and diabetic type 1), and massively obese humans with glucose intolerance. Results: When compared to non-obese controls, autotaxin expression in db/db mice was significantly increased, but not in GTG, HFD, or streptozotocin-treated mice. During db/db mice development, up-regulation of autotaxin occurred only 3 weeks after the emergence of hyperinsulinaemia, and simultaneously with the emergence of hyperglycaaemia. Adipocytes from db/db mice exhibited a stronger impairment of insulin-stimulated glucose uptake than non-obese and HFD-induced obese mice. Autotaxin expression was up-regulated by treatment with TNF alpha (insulin resistance-promoting cytokine), and down-regulated by rosiglitazone treatment (insulin-sensitising compound) in 3T3F442A adipocytes. Finally, adipose tissue autotaxin expression was significantly up-regulated in patients exhibiting both insulin resistance and impaired glucose tolerance. Conclusions/interpretation: The present work demonstrates the existence of a db/db-specific up-regulation of adipocyte autotaxin expression, which could be related to the severe type 2 diabetes phenotype and adipocyte insulin resistance, rather than excess adiposity in itself. It also showed that type 2 diabetes in humans is also associated with up-regulation of adipocyte autotaxin expression.