Hostname: page-component-669899f699-vbsjw Total loading time: 0 Render date: 2025-05-01T01:44:31.323Z Has data issue: false hasContentIssue false
  • English
  • Français

Tryptophan regulates food intake in growing pigs by modulating hypothalamic AMPK–mTOR signalling pathway

Published online by Cambridge University Press:  13 December 2024

Juexin Fan ,
Yuezhou Yao ,
Leli Wang ,
Feiyue Chen ,
Zhenguo Hu ,
Kaihuan Xie ,
Shuzhong Jiang  and
Xiongzhuo Tang Open the ORCID record for Xiongzhuo Tang [Opens in a new window]
Juexin Fan
Affiliation:
Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Science, Changsha, Hunan 410125, People’s Republic of China Hunan Jiuding Technology (Group) Co., Ltd, Changsha, Hunan 410007, People’s Republic of China
Yuezhou Yao
Affiliation:
Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, People’s Republic of China
Leli Wang
Affiliation:
Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Science, Changsha, Hunan 410125, People’s Republic of China
Feiyue Chen
Affiliation:
Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, People’s Republic of China
Zhenguo Hu
Affiliation:
Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Science, Changsha, Hunan 410125, People’s Republic of China
Kaihuan Xie
Affiliation:
Hunan Jiuding Technology (Group) Co., Ltd, Changsha, Hunan 410007, People’s Republic of China
Shuzhong Jiang*
Affiliation:
Hunan Jiuding Technology (Group) Co., Ltd, Changsha, Hunan 410007, People’s Republic of China
Xiongzhuo Tang*
Affiliation:
Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, People’s Republic of China Yuelushan Laboratory, Changsha, Hunan 410128, People’s Republic of China
*
Corresponding authors: Shuzhong Jiang; Email: [email protected]; Xiongzhuo Tang; Email: [email protected]
Corresponding authors: Shuzhong Jiang; Email: [email protected]; Xiongzhuo Tang; Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Tryptophan (Trp) is an essential amino acid acting as a key nutrition factor regulating animal growth and development. But how Trp modulates food intake in pigs is still not well known. Here, we investigated the effect of dietary supplementation of Trp with different levels on food intake of growing pigs. The data showed that dietary Trp supplementation with the standardised ileal digestibility (SID) Trp to lysine (Lys) ratio at both 0·18 and 0·20 significantly increased the food intake by activating the expression of orexigenic gene agouti-related peptide (AgRP) and inhibiting the expression of anorexigenic gene pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART) and melanocortin receptor 4 (MC4R) in the hypothalamus. Meanwhile, the level of anorexigenic hormones appetite-regulating peptide YY (PYY) in the duodenum and serum and leptin receptor in the duodenum were also significantly decreased. Importantly, both the kynurenine and serotonin metabolic pathways were activated upon dietary Trp supplementation to downregulate MC4R expression in the hypothalamus. Further mechanistic studies revealed that the reduced MC4R expression activated the hypothalamic AMP-activated protein kinase (AMPK) pathway, which in turn inhibited the mammalian target of rapamycin (mTOR)/S6 kinase 1 (S6K1) activity to stimulate food intake. Together, our study unravels the orexigenic effect of dietary Trp supplementation in pigs and expands its potential application in developing nutrition intervention strategy in pig production.

Keywords

Tryptophan metabolismPigsFood intakeHypothalamusmTOR
Type
Research Article
Information
British Journal of Nutrition , Volume 133 , Issue 2 , 28 January 2025 , pp. 269 - 276
Check for updates
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of The Nutrition Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

Footnotes

†

These authors contributed equally to this work.

References

Shouren, L, Mengqi, L, Shixi, C, et al. (2023) The mechanism of the gut-brain axis in regulating food intake. Nutrients 15, 3728.Google Scholar
Buhmann, H, le Roux, CW & Bueter, M (2014) The gut-brain axis in obesity. Best Pract Res Clin Gastroenterol 28, 559–571.CrossRefGoogle ScholarPubMed
Gregory, J, David, E, Denis, G, et al. (2006) Central nervous system control of food intake and body weight. Nature 443, 289–295.Google Scholar
Ulrika, A, Karin, F, Caroline, RA, et al. (2004) AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem 279, 12005–12008.Google Scholar
Yasuhiko, M, Thierry, A, Noboru, F, et al. (2004) AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428, 569–574.Google Scholar
Song, Z, Lei, L, Yunshuang, Y, et al. (2012) Fasting alters protein expression of AMP-activated protein kinase in the hypothalamus of broiler chicks (Gallus gallus domesticus). Gen Comp Endocrinol 178, 546–555.CrossRefGoogle ScholarPubMed
Daniela, C, Karine, P, Kathi, A, et al. (2006) Hypothalamic mTOR signaling regulates food intake. Science 312, 927–930.Google Scholar
Christopher, DM, Xiaochun, X, Christy, LW, et al. (2007) Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism. Am J Physiol Endocrinol Metab 293, E165–E171.Google Scholar
Ken, I, Tianqing, Z & Kun-Liang, G (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577–590.Google Scholar
Anne-Catherine, M, Alexandre, B, Anne, L, et al. (2014) Hypothalamic eIF2α signaling regulates food intake. Cell Rep 6, 438–444.Google Scholar
Dorothy, WG, Shuzhen, H & Tracy, GA (2007) Mechanisms of food intake repression in indispensable amino acid deficiency. Annu Rev Nutr 27, 63–78.Google Scholar
Eder, K, Peganova, S & Kluge, H (2001) Studies on the tryptophan requirement of piglets. Arch Tierernahrung 55, 281–297.CrossRefGoogle ScholarPubMed
Zheng, L, Wei, H, Cheng, C, et al. (2016) Supplementation of branched-chain amino acids to a reduced-protein diet improves growth performance in piglets: involvement of increased feed intake and direct muscle growth-promoting effect. Br J Nutr 115, 2236–2245.CrossRefGoogle ScholarPubMed
Xue, C, Li, G, Zheng, Q, et al. (2023) Tryptophan metabolism in health and disease. Cell Metab 35, 1304–1326.CrossRefGoogle ScholarPubMed
Hu, Z, Feng, L, Jiang, Q, et al. (2023) Intestinal tryptophan metabolism in disease prevention and swine production. Anim Nutr 15, 364–374.CrossRefGoogle ScholarPubMed
Lora, KH, Erin, EJ, Gregory, MS, et al. (2006) Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 51, 239–249.Google Scholar
Pfaffl, MW, Horgan, GW & Leo, D (2002) Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Research 9, e36.CrossRefGoogle Scholar
Rao, Z, Li, J, Shi, B, et al. (2021) Dietary tryptophan levels impact growth performance and intestinal microbial ecology in weaned piglets via tryptophan metabolites and intestinal antimicrobial peptides. Animals 11, 817–817.CrossRefGoogle ScholarPubMed
Liang, H, Dai, Z, Liu, N, et al. (2018) Dietary L-tryptophan modulates the structural and functional composition of the intestinal microbiome in weaned piglets. Front Microbiol 9, 0.CrossRefGoogle ScholarPubMed
Liu, JB, Yan, HL, Cao, SC, et al. (2019) The response of performance in grower and finisher pigs to diets formulated to different tryptophan to lysine ratios. Livestock Sci 222, 25–30.CrossRefGoogle Scholar
Gonçalves, JPR, Melo, ADB, Yang, Q, et al. (2024) Increased dietary Trp, Thr, and Met supplementation improves performance, health, and protein metabolism of weaned piglets under mixed management and poor housing conditions. Animals 14, 1143.CrossRefGoogle ScholarPubMed
Hu, Z, Feng, L, Jiang, Q, et al. (2023) Intestinal tryptophan metabolism in disease prevention and swine production. Anim Nutr 15, 364–374.CrossRefGoogle ScholarPubMed
Tossou, MC, Liu, H, Bai, M, et al. (2016) Effect of high dietary tryptophan on intestinal morphology and tight junction protein of weaned pig. Biomed Res Int 0, 1–6.CrossRefGoogle Scholar
Eder, K, Nonn, H, Kluge, H, et al. (2003) Tryptophan requirement of growing pigs at various body weights. J Anim Physiol Anim Nutr (Berl) 87, 336–346.CrossRefGoogle ScholarPubMed
Lin, Y, Jiang, Z, Yu, D, et al. (1999) Study on the tryptophan requirement of weanling piglets. Chin J Anim Nutr 0, 3.Google Scholar
Friedman, JM & Mantzoros, CS (2015) 20 years of leptin: from the discovery of the leptin gene to leptin in our therapeutic armamentarium. Metabolism 64, 1–4.CrossRefGoogle ScholarPubMed
Lafferty, RA, Flatt, PR & Irwin, N (2018) C-terminal degradation of PYY peptides in plasma abolishes effects on satiety and beta-cell function. Biochem Pharmacol 158, 95–102.CrossRefGoogle ScholarPubMed
Nagasawa, H, Suzuki, M, Sakagami, N, et al. (1989) Effects of chronic ingestion of anthranilic acid on lactation in mice. Asian-Australas J Anim Sci 2, 23.CrossRefGoogle Scholar
Hubbard, TD, Murray, IA & Perdew, GH (2015) Indole and tryptophan metabolism: endogenous and dietary routes to ah receptor activation. Drug Metab Dispos 43, 1522–1535.CrossRefGoogle ScholarPubMed
Holst, J & Deacon, C (2005) Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors. Diabetologia 48, 612–615.CrossRefGoogle ScholarPubMed
Lu, K, Chen, X, Deng, X, et al. (2021) Potential role of hypothalamic and plasma ghrelin in the feeding behavior of obese type 2 diabetic rats with intraventricular glucagon-like peptide-1 receptor agonist intervention. Obes Facts 14, 10–20.CrossRefGoogle ScholarPubMed
Voigt, J-P & Fink, H (2015) Serotonin controlling feeding and satiety. Behav Brain Res 277, 14–31.CrossRefGoogle ScholarPubMed
Tiligada, E & Wilson, JF (1989) Regulation of α-melanocyte–stimulating hormone release from superfused slices of rat hypothalamus by serotonin and the interaction of serotonin with the dopaminergic system inhibiting peptide release. Brain Res 503, 225–228.CrossRefGoogle ScholarPubMed
Supplementary material: File

Fan et al. supplementary material

Fan et al. supplementary material
Download Fan et al. supplementary material(File)
File 34.2 KB