Department of Foods & Nutrition, University of Georgia, Athens, GA 30602, USA.
Department of Food Science & Technology, University of Georgia, Athens, GA 30602, USA.
Int J Mol Sci. 2020 May 10;21(9):3368. doi: 10.3390/ijms21093368.
Gut-derived satiety hormones provide negative feedback to suppress food intake and maintain metabolic function in peripheral tissues. Despite the wealth of knowledge of the systemic effects of these hormones, very little is known concerning the mechanisms by which nutrients, such as dietary fats, can promote the expression of genes involved in L-cell hormone production. We have tested the role of various dietary fats and found that after hydrolysis into free fatty acids (FFA's), there is a differential response in the extent to which they induce PYY gene and protein production. The effect of FFA's also seems to relate to triglyceride (TG) re-esterification rate, with MUFA re-esterifying faster with lower PYY production. We have also found that there are differences in potency of FFA's based on their desaturation patterns in vitro. The potency effect of FFA's is influenced by the rate of TG re-esterification, such that the longer FFA's are in contact with L-cells, the more PYY they produce. We found that chronic consumption of high-fat diets enables the small intestine to re-esterify FFA's into TG faster and earlier which resulted in a blunted postprandial PYY response. Lastly, we found that FFA's induce X-box-binding protein-1 activation (Xbp1s) in L-cells and that adenoviral delivery of Xbp1s was sufficient to induce PYY gene expression. Taken together, the present work indicates that dietary fat can induce satiety, in part, prior to re-esterification. Chronic high-fat diet consumption increases the rate of re-esterification which diminishes satiety and may lead to increased food intake. Targeting intestinal TG synthesis may prove beneficial in restoring obesity-associated reductions in postprandial satiety.
肠源饱腹感激素通过负反馈抑制食物摄入并维持外周组织的代谢功能。尽管人们对这些激素的系统作用有了丰富的认识，但对于营养素（如膳食脂肪）如何促进与 L 细胞激素产生相关的基因表达的机制却知之甚少。我们已经测试了各种膳食脂肪的作用，发现它们在水解成游离脂肪酸（FFA）后，诱导 PYY 基因和蛋白产生的程度存在差异。FFA 的作用似乎也与甘油三酯（TG）再酯化率有关，MUFA 再酯化更快，PYY 产生量更低。我们还发现，FFA 的体外饱和模式存在效力差异。FFA 的效力受 TG 再酯化率的影响，因此 FFA 与 L 细胞接触的时间越长，产生的 PYY 就越多。我们发现，长期食用高脂肪饮食使小肠能够更快更早地将 FFA 再酯化回 TG，从而导致餐后 PYY 反应迟钝。最后，我们发现 FFA 可诱导 L 细胞中 X 盒结合蛋白-1 激活（Xbp1s），而腺病毒传递 Xbp1s 足以诱导 PYY 基因表达。总之，本研究表明，膳食脂肪可以在再酯化之前部分诱导饱腹感。慢性高脂肪饮食摄入会增加再酯化的速度，从而降低饱腹感，并可能导致食物摄入增加。靶向肠道 TG 合成可能有助于恢复与肥胖相关的餐后饱腹感降低。
