Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea.
Endocrinol Metab (Seoul). 2020 Jun;35(2):470-479. doi: 10.3803/EnM.2020.35.2.470. Epub 2020 Jun 24.
Obesity is defined as excessive fat mass and is a major cause of many chronic diseases such as diabetes, cardiovascular disease, and cancer. Increasing energy expenditure and regulating adipose tissue metabolism are important targets for the treatment of obesity. Serotonin (5-hydroxytryptophan [5-HT]) is a monoamine metabolite of the essential amino acid tryptophan. Here, we demonstrated that 5-HT in mature adipocytes regulated energy expenditure and lipid metabolism.
Tryptophan hydroxylase 1 (TPH1) is the rate-limiting enzyme during 5-HT synthesis in non-neural peripheral tissues. We generated adipose tissue-specific Tph1 knockout (Tph1 FKO) mice and adipose tissue-specific serotonin receptor 2A KO (Htr2a FKO) mice and analyzed their phenotypes during high-fat diet (HFD) induced obesity.
Tph1 FKO mice fed HFD exhibited reduced lipid accumulation, increased thermogenesis, and resistance to obesity. In addition, Htr2a FKO mice fed HFD showed reduced lipid accumulation in white adipose tissue and resistance to obesity.
These data suggest that the inhibition of serotonin signaling might be an effective strategy in obesity.
肥胖被定义为脂肪过多，是许多慢性疾病（如糖尿病、心血管疾病和癌症）的主要原因。增加能量消耗和调节脂肪组织代谢是治疗肥胖的重要目标。血清素（5-羟色氨酸[5-HT]）是必需氨基酸色氨酸的单胺代谢物。在这里，我们证明成熟脂肪细胞中的 5-HT 可调节能量消耗和脂质代谢。
色氨酸羟化酶 1（TPH1）是神经外周围组织中 5-HT 合成的限速酶。我们生成了脂肪组织特异性 Tph1 敲除（Tph1 FKO）小鼠和脂肪组织特异性 5-羟色胺受体 2A 敲除（Htr2a FKO）小鼠，并在高脂肪饮食（HFD）诱导肥胖期间分析了它们的表型。
喂食 HFD 的 Tph1 FKO 小鼠表现出脂质积累减少、产热增加和肥胖抵抗。此外，喂食 HFD 的 Htr2a FKO 小鼠白色脂肪组织中的脂质积累减少，肥胖抵抗。
这些数据表明抑制血清素信号可能是肥胖的有效策略。
