Department of Animal Science, California Polytechnic State University, San Luis Obispo, California.
Department of Food Science and Nutrition, California Polytechnic State University, San Luis Obispo, California.
Am J Physiol Endocrinol Metab. 2022 Sep 1;323(3):E187-E206. doi: 10.1152/ajpendo.00052.2022. Epub 2022 Jul 20.
The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-day-old Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: ) lard-enriched (LAR; = 5 pens), ) olive oil-enriched (OLI; = 5), and ) coconut oil-enriched (COC; = 5). Animals were euthanized on after blood sampling, and liver, colon, and distal ileum (DI) were collected for histology, metabolomics, and transcriptomics. Data were analyzed by multivariate and univariate statistics. Compared with OLI and LAR, COC increased primary and secondary BAs in liver, plasma, and colon. In addition, both COC and OLI reduced circulating fibroblast growth factor 19, increased hepatic necrosis, composite lesion score, and liver enzymes in serum, and upregulated genes involved in hepatocyte proliferation and DNA repair. The severity of liver disease in COC and OLI pigs was associated with increased levels of phosphatidylcholines, medium-chain triacylglycerides, trimethylamine-N-oxide, and long-chain acylcarnitines in the liver, and the expression of profibrotic markers in DI, but not with changes in the composition or size of BA pool. In conclusion, our results indicate a role of dietary FAs in the regulation of BA metabolism and progression of NAFLD. Interventions that aim to modify the composition of dietary FAs, rather than to regulate BA metabolism or signaling, may be more effective in the treatment of NAFLD. Bile acid homeostasis and signaling is disrupted in NAFLD and may play a central role in the development of the disease. However, there are no studies addressing the impact of diet on bile acid metabolism in patients with NAFLD. In juvenile Iberian pigs, we show that fatty acid composition in high-fat high-fructose diets affects BA levels in liver, plasma, and colon but these changes were not associated with the severity of the disease.
本研究旨在通过多组学方法结合组织学和血清生化分析，研究饲粮脂肪酸（FA）组成对非酒精性脂肪性肝病（NAFLD）猪模型胆汁酸（BA）代谢的影响。30 头 20 日龄伊比利亚猪成对饲养在猪舍中，随机分为 3 组接受 10 周高卡路里饮食：）富含猪油（LAR；n = 5 个栏），）富含橄榄油（OLI；n = 5）和）富含椰子油（COC；n = 5）。动物在采血后 1 周内安乐死，收集肝脏、结肠和回肠远端（DI）进行组织学、代谢组学和转录组学分析。采用多变量和单变量统计方法进行数据分析。与 OLI 和 LAR 相比，COC 增加了肝脏、血浆和结肠中的初级和次级 BA。此外，COC 和 OLI 均降低了循环成纤维细胞生长因子 19，增加了肝坏死、综合病变评分和血清中肝酶，并上调了参与肝细胞增殖和 DNA 修复的基因。COC 和 OLI 猪的肝病严重程度与肝脏中磷脂酰胆碱、中链三酰甘油、三甲胺 N-氧化物和长链酰基辅酶 A 的水平升高以及 DI 中纤维生成标记物的表达有关，但与 BA 池的组成或大小变化无关。总之，我们的研究结果表明，饲粮 FA 组成在调节 BA 代谢和 NAFLD 进展中起作用。旨在改变饲粮 FA 组成而不是调节 BA 代谢或信号的干预措施可能更有效地治疗 NAFLD。NAFLD 患者的 BA 代谢存在失衡，并可能在疾病的发生发展中起核心作用。然而，目前还没有研究探讨饮食对 NAFLD 患者 BA 代谢的影响。在幼年伊比利亚猪中，我们表明高脂肪高果糖饮食中的脂肪酸组成会影响肝脏、血浆和结肠中的 BA 水平，但这些变化与疾病的严重程度无关。
