Adipose dysfunction is the primary defect in obesity that contributes to the development of dyslipidemia, insulin resistance, cardiovascular diseases, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and some cancers. Previously, we demonstrated the development of NAFLD in lipocalin-type prostaglandin D₂ synthase (L-PGDS) knockout mice regardless of diet. In the present study, we examined the role of L-PGDS in adipose in response to a high fat diet. We observed decreased expression of L-PGDS in adipose tissue and concomitant lower plasma levels in a dietary model of obesity as well as in insulin resistant 3T3-L1 adipocytes. We show reduced adiponectin expression and phosphorylation of AMPK in white adipose tissue of L-PGDS KO mice after 14 weeks on a high fat diet as compared to control C57BL/6 mice. We also observe an increased fat content in L-PGDS KO mice as demonstrated by adipocyte hypertrophy and increased expression of lipogenenic genes. We confirmed our in vivo findings in in vitro 3T3-L1 adipocytes, using an enzymatic inhibitor of L-PGDS (AT56). Rosiglitazone treatment drastically increased L-PGDS expression in insulin resistant 3T3-L1 adipocytes and increased adiponectin expression and AMPK phosphorylation in AT56 treated 3T3-L1 adipocytes. We conclude that the absence of L-PGDS has a deleterious effect on adipose tissue functioning, which further reduces insulin sensitivity in adipose tissue. Consequently, we propose L-PGDS appears to function as a potential member of the adipokine secretome involved in the regulation of the obesity-associated metabolic syndrome.

脂肪功能障碍是肥胖的主要缺陷，导致血脂异常、胰岛素抵抗、心血管疾病、2型糖尿病、非酒精性脂肪肝疾病 (NAFLD) 和一些癌症的发展。以前，我们展示了脂质运载蛋白型前列腺素 D _{2中 NAFLD 的发展}无论饮食如何，合酶（L-PGDS）敲除小鼠。在本研究中，我们检查了 L-PGDS 在脂肪中对高脂肪饮食的反应。我们观察到脂肪组织中 L-PGDS 的表达降低，同时在肥胖饮食模型和胰岛素抵抗 3T3-L1 脂肪细胞中血浆水平降低。与对照 C57BL/6 小鼠相比，在高脂饮食 14 周后，我们显示 L-PGDS KO 小鼠白色脂肪组织中脂联素表达和 AMPK 磷酸化降低。我们还观察到 L-PGDS KO 小鼠的脂肪含量增加，如脂肪细胞肥大和脂肪生成基因表达增加所证明的那样。我们在体外证实了我们的体内发现3T3-L1 脂肪细胞，使用 L-PGDS (AT56) 的酶抑制剂。罗格列酮治疗显着增加了胰岛素抵抗 3T3-L1 脂肪细胞中 L-PGDS 的表达，并增加了 AT56 处理的 3T3-L1 脂肪细胞中的脂联素表达和 AMPK 磷酸化。我们得出结论，L-PGDS 的缺乏对脂肪组织功能有有害影响，这进一步降低了脂肪组织中的胰岛素敏感性。因此，我们提出 L-PGDS 似乎作为参与调节肥胖相关代谢综合征的脂肪因子分泌组的潜在成员发挥作用。