色氨酸及其代谢物调控糖脂代谢的研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2025-1029

摘要/Abstract

摘要：

色氨酸是一种必需氨基酸，可经犬尿氨酸途径、5-羟色胺途径和吲哚途径产生多种具有生物活性的代谢产物，广泛参与氧化应激、炎症反应和免疫应答等生理过程。近来研究表明，色氨酸代谢不仅是维持宿主健康与肠道微生态平衡的重要枢纽，其代谢紊乱还与肥胖、2型糖尿病、高脂血症以及代谢相关脂肪性肝病等一系列代谢性疾病的发生和发展密切相关。色氨酸代谢可通过调节糖脂代谢、胰岛素信号转导和免疫稳态等途径影响疾病进程。靶向调控色氨酸代谢限速酶的活性，如色氨酸-2,3-双加氧酶、吲哚胺-2,3-双加氧酶和犬尿氨酸单加氧酶，能够干预关键代谢物的生成，从而纠正代谢失衡、减轻炎症或改善细胞功能，有望为多种疾病的治疗提供新策略。本文聚焦于色氨酸关键代谢产物的病理生理功能，系统综述了色氨酸代谢在肝脏、肠道、脂肪组织和胰腺中的器官特异性调控机制，阐释了犬尿氨酸的促炎作用和胰岛素抵抗效应、5-羟色胺对糖脂代谢的双重调节作用，并强调了吲哚丙酸等肠道菌群产生的吲哚类衍生物通过抗炎、抗氧化和保护肠道屏障等功能缓解机体代谢紊乱的作用。此外，本文进一步探讨了色氨酸代谢产物作为信号分子，通过“肠-肝轴”调节肝脏脂质代谢与炎症反应，以及通过“肠-脑轴”调控食欲与能量平衡的跨器官通讯机制，旨在为色氨酸及其代谢物在糖脂代谢紊乱相关疾病的诊断和治疗方面提供理论依据。

关键词: 色氨酸, 5-羟色胺, 代谢性疾病, “肠-肝轴”

Abstract:

Tryptophan (Trp) is an essential amino acid that generates a diverse array of bioactive metabolites via the kynurenine, serotonin, and indole pathways, participating extensively in physiological processes such as oxidative stress, inflammatory responses, and immune responses. Recent studies indicate that Trp metabolism serves not only as a pivotal hub maintaining host health and gut micro-ecological balance, but its dysregulation is also closely associated with the onset and progression of a spectrum of metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), hyperlipidemia, and metabolic dysfunction-associated fatty liver disease (MAFLD). Trp metabolism influences disease progression by modulating glucose and lipid metabolism, insulin signal transduction, and immune homeostasis. Targeting the activity of rate-limiting enzymes in Trp metabolism—such as tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO), and kynurenine 3-monooxygenase (KMO)—can intervene in the production of key metabolites, thereby correcting metabolic imbalances, alleviating inflammation, or improving cellular function. This approach holds promise as a novel therapeutic strategy for various diseases. This review focuses on the pathophysiological functions of key Trp metabolites and systematically summarizes the organ-specific regulatory mechanisms of Trp metabolism in the liver, intestine, adipose tissue, and pancreas. It elucidates the pro-inflammatory effects and insulin resistance associated with kynurenine, the dual regulatory roles of serotonin in glucose and lipid metabolism, and highlights the capacity of gut microbiota-derived indole derivatives, such as indolepropionic acid, to alleviate metabolic disorders via anti-inflammatory, antioxidant, and gut barrier protection mechanisms. Furthermore, this article explores the inter-organ communication mechanisms where Trp metabolites act as signaling molecules to regulate hepatic lipid metabolism and inflammation via the “gut-liver axis”, and modulate appetite and energy balance via the “gut-brain axis”. These insights aim to provide a theoretical basis for the diagnosis and treatment of diseases related to glucose and lipid metabolic disorders.

Key words: tryptophan, serotonin, metabolic diseases, “gut-liver axis”

王丹, 黄泓杰, 曹随忠, 黄逸馨. 色氨酸及其代谢物调控糖脂代谢的研究进展[J]. 生物技术通报, 2026, 42(7): 11-21.

WANG Dan, HUANG Hong-jie, CAO Sui-zhong, HUANG Yi-xin. Advances in the Regulation of Glucose and Lipid Metabolism by Tryptophan and Its Metabolites[J]. Biotechnology Bulletin, 2026, 42(7): 11-21.

图/表 3

图1 色氨酸代谢在各器官中的调控作用Intestine：肠道；liver：肝脏；Fatty acid synthesis：脂肪酸合成；Lipid absorption：脂质吸收；Hepatocyte：肝细胞；Lipogenesis：脂肪生成；Mast cell：肥大细胞；White adipocyte：白色脂肪细胞；Thermogenesis：产热；Brown adipocyte：棕色脂肪细胞；Adipose tissue：脂肪组织；Insulin secretion：胰岛素分泌；Pancreatic β-cell：胰腺β细胞；Glucagon secretion：胰高血糖素分泌；Pancreatic α-cell：胰腺α细胞；Pancreas：胰腺；Trp：色氨酸；5-HT：5-羟色胺（血清素）；IAA：吲哚-3-乙酸；IALD：吲哚-3-甲醛；ILA：吲哚-3-乳酸；AhR：芳香烃受体；IL-22：白细胞介素-22；TPH1：色氨酸羟化酶1；TDO：色氨酸-2，3-双加氧酶；KYN：犬尿氨酸；NAD⁺：烟酰胺腺嘌呤二核苷酸；MLT：褪黑素；SREBP：固醇调节元件结合蛋白；PPARγ：过氧化物酶体增殖物激活受体γ；HTR2A：5-羟色胺受体2A；IDO：吲哚胺-2，3-双加氧酶；STAT3：信号转导及转录激活蛋白3；IL-6：白细胞介素-6；UCP-1：解偶联蛋白1；HTR2C：5-羟色胺受体2C；5-HT1F：5-羟色胺受体1F。图片基于BioRender网站生成

Fig. 1 Regulatory role of tryptophan metabolism in various organsTrp： Tryptophan. 5-HT： 5-Hydroxytryptamine. IAA： Indole-3-acetic acid. IALD： Indole-3-aldehyde. ILA： Indole-3-lactic acid. Ahr： Aryl hydrocarbon receptor. IL-22： Interleukin-22. TPH1： Tryptophan hydroxylase 1. TDO： Tryptophan 2，3-dioxygenase. KYN： Kynurenine. NAD⁺： Nicotinamide adenine dinucleotide. MLT： Melatonin. SREBP： Sterol regulatory element-binding protein. PPARγ： Peroxisome proliferator-activated receptor gamma. HTR2A： 5-Hydroxytryptamine receptor 2A. IDO： Indoleamine 2，3-dioxygenase. STAT3： Signal transducer and activator of transcription 3. IL-6： Interleukin-6. UCP-1： Uncoupling protein 1. HTR2C： 5-Hydroxytryptamine receptor 2C. 5-HT1F： 5-Hydroxytryptamine receptor 1F. Figure was created with BioRender

表1 色氨酸代谢产物的调节作用及靶点

Table 1 Regulatory roles and targets of tryptophan metabolites

色氨酸代谢产物 Tryptophan metabolites	关键酶 Key enzymes	代谢物来源 Source	代谢调控作用 Metabolic regulatory function	作用靶点 Action target	参考文献 Reference
KYN	IDO	脂肪细胞	诱导肥胖和胰岛素抵抗	AhR-STAT3-IL-6	［46］
3-HK	KMO	胰岛β细胞	诱导胰岛素抵抗	-	［52］
KYNA	KAT	肝细胞	改善肝脏脂肪变性	AMPK/ORP150	［32］
NAD⁺	ACMSD	肝细胞	减轻脂肪肝	-	［30］
5-HT	TPH1	肠道嗜铬细胞	促进肠道蠕动	-	［24］
	-	产芽孢细菌	促进肠道脂质吸收	-	［8］
	TPH1	肥大细胞	诱导肝脏脂质累积	HTR2A-PPARγ	［34］
	TPH1	白色脂肪细胞	促进脂肪生成	HTR2A	［41］
	TPH1	棕色脂肪细胞	抑制脂肪分解	UCP1	［43］
	TPH1	胰岛β细胞	抑制胰岛α细胞释放胰高血糖素	5-HT1F受体	［53］
	TPH1	胰岛β细胞	抑制胰岛β细胞分泌胰岛素	HTR2C	［55］
MLT	AANAT	肝细胞	减轻肝脏脂质累积	SREBP-1c	［37］
IPA	ACD	肠道菌群	改善胰岛素敏感性，减少脂质累积	FFAR3-IL-25、NFκB	［18-19］
IAlD	-	肠道菌群	改善胰岛素敏感性，抗肥胖	AhR、Nrf2	［20］

图2 色氨酸代谢在器官间的互作Portal vein：门静脉；Suppress appetite：抑制食欲；Leptin：瘦素；STAT3：信号转导及转录激活蛋白3；HTR2C：5-羟色胺受体2C；5-HT：5-羟色胺（血清素）；TPH2：色氨酸羟化酶2；Trp：色氨酸；POMC neurons：阿片黑素皮质素原神经元；IPA：吲哚-3-丙酸；BA：胆汁酸；TPH1：色氨酸羟化酶1；FXR：法尼醇X受体；FGF15/19：成纤维细胞生长因子15/19；FGFR4：成纤维细胞生长因子受体4；CYP7A1：胆固醇7α-羟化酶；HTR2A：5-羟色胺受体2A；HTR2B：5-羟色胺受体2B；PPARγ：过氧化物酶体增殖物激活受体γ；Hepatocyte：肝细胞；Lipogenesis：脂肪生成。图片基于BioRender网站生成

Fig. 2 Tryptophan metabolism in inter-organ crosstalkSTAT3： Signal transducer and activator of transcription 3. HTR2C： 5-Hydroxytryptamine receptor 2C. 5-HT： 5-Hydroxytryptamine. TPH2： Tryptophan hydroxylase 2. Trp： Tryptophan. POMC Neurons： Pro-opiomelanocortin neurons. IPA： Indole-3-propionic acid. BA： Bile acids. TPH1： Tryptophan hydroxylase 1. FXR： Farnesoid X receptor. FGF15/19： Fibroblast growth factor 15/19. FGFR4： Fibroblast growth factor receptor 4. CYP7A1： Cholesterol 7 alpha-hydroxylase （Cytochrome P450 Family 7 Subfamily A Member 1）. HTR2A： 5-Hydroxytryptamine receptor 2A. HTR2B： 5-Hydroxytryptamine receptor 2B. PPARγ： Peroxisome proliferator-activated receptor gamma. Hepatocyte： Hepatocyte. Lipogenesis： Lipogenesis. Figure was created with BioRender

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