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脂联素类似物 ALY688 对内脏和皮下大鼠脂肪细胞葡萄糖和脂肪代谢的影响。

Effects of the adiponectin mimetic compound ALY688 on glucose and fat metabolism in visceral and subcutaneous rat adipocytes.

机构信息

School of Kinesiology and Health Science, York University , North York, Canada.

Department of Biology, York University , North York, Canada.

出版信息

Adipocyte. 2020 Dec;9(1):550-562. doi: 10.1080/21623945.2020.1817230.

DOI:10.1080/21623945.2020.1817230
PMID:32897149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7714433/
Abstract

Adiponectin regulates white adipose tissue (WAT) metabolism and promotes insulin-sensitizing and anti-atherosclerotic effects . In this context, small molecule adiponectin receptor agonists have become of great therapeutic value for the treatment of metabolic diseases. Here, we investigated the effects of the adiponectin mimetic compound ALY688 on WAT metabolism. To accomplish this, rat epididymal (Epid) and subcutaneous inguinal (Sc Ing) adipocytes were isolated and incubated with ALY688. Subsequently, several parameters of glucose and fat metabolism were assessed. ALY688 promoted AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, enhanced glucose oxidation, and suppressed fat oxidation in adipocytes from both fat depots. ALY688 did not affect basal and insulin-stimulated rates of glucose uptake, glucose incorporation into lipids, and AKT and p38 mitogen-activated protein kinase (MAPK) phosphorylations in either Epid or Sc Ing adipocytes. ALY688 did not alter basal lipolysis in Epid and Sc Ing adipocytes, but it enhanced isoproterenol-induced lipolysis in Epid adipocytes. Adiponectin receptor 2 (AdipoR2) mRNA was the prevalent isoform expressed in all adipocytes, and Epid adipocytes displayed significantly higher AdipoR2 mRNA expression than Sc Ing adipocytes. In conclusion, ALY688 can regulate adiposity and affect glycaemic control by altering substrate portioning in the WAT in a fat depot-specific manner.

摘要

脂联素调节白色脂肪组织（WAT）代谢，并具有促进胰岛素敏感性和抗动脉粥样硬化的作用。在这种情况下，小分子脂联素受体激动剂在治疗代谢性疾病方面具有重要的治疗价值。在这里，我们研究了脂联素模拟化合物 ALY688 对 WAT 代谢的影响。为了实现这一目标，我们分离了大鼠附睾（Epid）和皮下腹股沟（Sc Ing）脂肪细胞，并将它们与 ALY688 孵育。随后，评估了几种葡萄糖和脂肪代谢参数。ALY688 促进了 AMP 激活的蛋白激酶（AMPK）和乙酰辅酶 A 羧化酶（ACC）的磷酸化，增强了脂肪细胞的葡萄糖氧化作用，并抑制了脂肪细胞的脂肪氧化作用，无论是来自 Epid 还是 Sc Ing 脂肪细胞。ALY688 不影响基础和胰岛素刺激的葡萄糖摄取率、葡萄糖向脂质的掺入率，以及在 Epid 或 Sc Ing 脂肪细胞中 AKT 和 p38 丝裂原激活蛋白激酶（MAPK）的磷酸化。ALY688 不改变 Epid 和 Sc Ing 脂肪细胞的基础脂肪分解，但它增强了 Epid 脂肪细胞中异丙肾上腺素诱导的脂肪分解。脂联素受体 2（AdipoR2）mRNA 是所有脂肪细胞中表达的主要同工型，并且 Epid 脂肪细胞中 AdipoR2 mRNA 的表达明显高于 Sc Ing 脂肪细胞。总之，ALY688 可以通过以脂肪组织特异性的方式改变 WAT 中的底物分配来调节肥胖和影响血糖控制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/25d79bf292bc/KADI_A_1817230_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/f082dfd4a467/KADI_A_1817230_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/2cc4f0292f04/KADI_A_1817230_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/39a00012ea79/KADI_A_1817230_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/bebd99741f04/KADI_A_1817230_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/d372bec0457e/KADI_A_1817230_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/beb25f19a2d2/KADI_A_1817230_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/a0803394bee7/KADI_A_1817230_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/25d79bf292bc/KADI_A_1817230_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/f082dfd4a467/KADI_A_1817230_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/2cc4f0292f04/KADI_A_1817230_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/39a00012ea79/KADI_A_1817230_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/bebd99741f04/KADI_A_1817230_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/d372bec0457e/KADI_A_1817230_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/beb25f19a2d2/KADI_A_1817230_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/a0803394bee7/KADI_A_1817230_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6753/7714433/25d79bf292bc/KADI_A_1817230_F0008_B.jpg

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