University of Cambridge, Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Sci Rep. 2018 Jan 8;8(1):74. doi: 10.1038/s41598-017-18259-0.
Peptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models. The effect was predominantly attributable to the histone deacetylase inhibitory activity of SCFA and minor, but significant contributions of FFA2 (GPR43). Consistent with the SCFA-dependent elevation of PYY gene expression, we also observed increased basal and stimulated PYY hormone secretion. Interestingly, the transcriptional stimulation of PYY was specific to human-derived cell models and not reproduced in murine primary cultures. This is likely due to substantial differences in PYY gene structure between mouse and human. In summary, this study revealed a strong regulation of PYY production by SCFA that was evident in humans but not mice, and suggests that high fibre diets elevate plasma concentrations of the anorexigenic hormone PYY, both by targeting gene expression and hormone secretion.
肽 YY（PYY）和胰高血糖素样肽-1（GLP-1）在调节食物摄入和胰岛素分泌方面发挥着重要作用，它们在肥胖和糖尿病领域的转化研究中具有重要意义。PYY 的产生在位于远端肠道的肠内分泌细胞中最高，反映了肠道微生物群产生短链脂肪酸（SCFA）的高浓度部位。我们在这里表明，丙酸盐和丁酸盐强烈增加了人细胞系和肠原代培养模型中 PYY 的表达，但对 GCG 的表达没有影响。这种作用主要归因于 SCFA 的组蛋白去乙酰化酶抑制活性，而游离脂肪酸 2（GPR43）的作用较小，但也很重要。与 SCFA 依赖性 PYY 基因表达升高一致，我们还观察到基础和刺激后 PYY 激素分泌增加。有趣的是，PYY 的转录刺激特异性于人源细胞模型，而在鼠原代培养物中无法重现。这可能是由于人和鼠 PYY 基因结构存在很大差异。总之，这项研究揭示了 SCFA 对 PYY 产生的强烈调节作用，这种作用在人类中很明显，但在小鼠中却没有，这表明高纤维饮食通过靶向基因表达和激素分泌来提高厌食激素 PYY 的血浆浓度。
