Department of Pathobiochemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Laboratory of Chemical Pharmacology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka, 815-8511, Japan.
Sci Rep. 2019 Feb 13;9(1):1931. doi: 10.1038/s41598-018-38453-y.
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is responsible for the production of PGD in adipocytes and is selectively induced by a high-fat diet (HFD) in adipose tissue. In this study, we investigated the effects of HFD on obesity and insulin resistance in two distinct types of adipose-specific L-PGDS gene knockout (KO) mice: fatty acid binding protein 4 (fabp4, aP2)-Cre/L-PGDS and adiponectin (AdipoQ)-Cre/L-PGDS mice. The L-PGDS gene was deleted in adipocytes in the premature stage of the former strain and after maturation of the latter strain. The L-PGDS expression and PGD production levels decreased in white adipose tissue (WAT) under HFD conditions only in the aP2-Cre/L-PGDS mice, but were unchanged in the AdipoQ-Cre/L-PGDS mice. When fed an HFD, aP2-Cre/L-PGDS mice significantly reduced body weight gain, adipocyte size, and serum cholesterol and triglyceride levels. In WAT of the HFD-fed aP2-Cre/L-PGDS mice, the expression levels of the adipogenic, lipogenic, and M1 macrophage marker genes were decreased, whereas those of the lipolytic and M2 macrophage marker genes were enhanced or unchanged. Insulin sensitivity was improved in the HFD-fed aP2-Cre/L-PGDS mice. These results indicate that PGD produced by L-PGDS in premature adipocytes is involved in the regulation of body weight gain and insulin resistance under nutrient-dense conditions.
脂联素型前列腺素 D 合酶（L-PGDS）负责在脂肪细胞中产生 PGD，并在脂肪组织中被高脂肪饮食（HFD）选择性诱导。在这项研究中，我们研究了 HFD 对两种不同类型脂肪特异性 L-PGDS 基因敲除（KO）小鼠肥胖和胰岛素抵抗的影响：脂肪酸结合蛋白 4（fabp4，aP2）-Cre/L-PGDS 和脂联素（AdipoQ）-Cre/L-PGDS 小鼠。前者的 L-PGDS 基因在脂肪细胞的早期阶段，后者在成熟后被删除。只有在 aP2-Cre/L-PGDS 小鼠中，白色脂肪组织（WAT）中的 L-PGDS 表达和 PGD 产生水平在 HFD 条件下降低，但在 AdipoQ-Cre/L-PGDS 小鼠中没有变化。当喂食 HFD 时，aP2-Cre/L-PGDS 小鼠体重增加、脂肪细胞大小、血清胆固醇和甘油三酯水平显著降低。在 HFD 喂养的 aP2-Cre/L-PGDS 小鼠的 WAT 中，脂肪生成、脂生成和 M1 巨噬细胞标记基因的表达水平降低，而脂解和 M2 巨噬细胞标记基因的表达水平增强或不变。HFD 喂养的 aP2-Cre/L-PGDS 小鼠的胰岛素敏感性得到改善。这些结果表明，在营养丰富的条件下，L-PGDS 在早期脂肪细胞中产生的 PGD 参与了体重增加和胰岛素抵抗的调节。
