L-phenylalanine Increased Gut Hormone Secretion through Calcium-Sensing Receptor in the Porcine Duodenum.

Jiangyin Feng,Suqin Hang,Liren Ding,Chao Wang,Cuicui Kang,Weiyun Zhu

doi:10.3390/ani9080476

Abstract

Simple SummaryThe proper modulation of feed intake not only meets the nutrient requirement for the maximum growth rate in pigs, but also avoids feed waste. A complete understanding of how dietary factors affect the appetite in pigs will provide a strategy to modulate the feed intake of pigs. L-phenylalanine (L-Phe) has been demonstrated to induce satiety through stimulating anorectic hormone secretion in rodents. However, whether L-Phe has similar effects in pigs is unknown. Here, we aimed to investigate how L-Phe affects gut hormone secretion, along with insight into the underlying mechanism in porcine duodenum by using an in vitro perfusion system. Results showed that 80 mM L-Phe triggered glucose-dependent insulinotropic peptide (GIP) and cholecystokinin (CCK) release, and also upregulated calcium-sensing receptor (CaSR) and its downstream molecules, such as protein kinase C (PKC) and inositol 1,4,5-triphosphate receptor (IP3R) expression. However, these effects were attenuated by treatment with a CaSR antagonist. Our findings show that CaSR participates in Phe-induced hormone secretion in pig duodenum, indicating that CaSR may be a potential target in the food intake regulation of pigs.Luminal amino acids have a pivotal role in gut hormone secretion, and thereby modulate food intake and energy metabolism. However, the mechanisms by which amino acids exert this effect remains unknown. The purpose of this research was to investigate the response of L-phenylalanine (L-Phe) to gut hormone secretion and its underlying mechanisms by perfusing the pig duodenum. Eighty mM L-Phe and extracellular Ca2+ stimulated cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP) release, and upregulated the mRNA expression of the calcium-sensing receptor (CaSR), CCK, and GIP. Western blotting results showed that L-Phe also elevated the protein levels of CaSR, the inositol 1,4,5-triphosphate receptor (IP3R), and protein kinase C (PKC). However, the CaSR inhibitor NPS 2143 reduced the mRNA expression of CaSR, CCK, and GIP, and the secretion of CCK and GIP, as well as the protein level of CaSR, IP3R, and PKC. These results indicated that Phe stimulated gut secretion through a CaSR-mediated pathway and its downstream signaling molecules, PKC and IP3R.

Highlights

In commercial pig production, it is critical to meet the maximum growth rate nutrient requirement without wasting feed, emphasizing the importance of understanding how dietary factors can affect the feed intake of pigs [1]
To determine whether Phe regulated CCK and glucose-dependent insulinotropic peptide (GIP) secretion, the mRNA expression of calcium-sensing receptor (CaSR), CCK, and GIP and secretion of the two gut hormones were determined after treatment with the different
CaSR expression was observed in the pig duodenum (Figure 2a)

Summary

Introduction

It is critical to meet the maximum growth rate nutrient requirement without wasting feed, emphasizing the importance of understanding how dietary factors can affect the feed intake of pigs [1]. Evidences suggest that a high-protein diet is capable of suppressing food intake and reducing weight gain, and these effects may be associated with the sensing of its degradation. Animals 2019, 9, 476 products, especially amino acids in the gastrointestinal tract (GIT) [2,3]. Amino acids are an essential ingredient of swine diets, and are extensively generated by protein digestion in the small intestine. Identifying the mechanisms underlying amino acid-induced satiety will contribute to more effective nutritional manipulation for the modulation of feed intake in porcine production. Luminal amino acids function as the building blocks of proteins, as well as an essential releaser of anorexigenic gut hormones to enhance satiety [4]. Various types of amino acids exert different effects on gut peptide secretion, due to their specific structural characteristics and physicochemical properties [5]

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