Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, 78245-0549, USA.
Endocrinology and Metabolism, Department of Health Science, University of Milan, Via A. di Rudini, 8, 20142, Milan, Italy.
Acta Diabetol. 2019 Feb;56(2):227-236. doi: 10.1007/s00592-019-01286-w. Epub 2019 Jan 23.
Ectopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity.
Duodenal tissues were collected from aged (21.2 ± 1.3 years, 19.5 ± 3.1 kg, n = 39) female baboons (Papio sp.). Fasted blood was collected for metabolic profiling and abdominal circumference (AC) measurements were taken. Primary tissue samples were collected at the major duodenal papilla at necropsy: one full cross section was processed for hematoxylin and eosin staining and evaluated; a second full cross section was processed for direct chemical lipid analysis on which percentage duodenal fat content was calculated.
Duodenal fat content obtained by direct tissue quantification showed considerable variability (11.95 ± 6.93%) and was correlated with AC (r = 0.60, p < 0.001), weight (r = 0.38, p = 0.02), leptin (r = 0.63, p < 0.001), adiponectin (r = - 0.32, p < 0.05), and triglyceride (r = 0.41, p = 0.01). The relationship between duodenal fat content and leptin remained after adjusting for body weight and abdominal circumference. Intramural adipocytes were found in duodenal sections from all animals and were localized to the submucosa. Consistent with the variation in tissue fat content, the submucosal adipocytes were non-uniformly distributed in clusters of varying size. Duodenal adipocytes were larger in obese vs. lean animals (106.9 vs. 66.7 µm, p = 0.02).
Fat accumulation inside the duodenal wall is strongly associated with adiposity and adiposity related circulating biomarkers in baboons. Duodenal tissue fat represents a novel and potentially metabolically active site of ectopic fat deposition.
异位脂肪是胰岛素抵抗和代谢功能障碍的公认原因,而肠壁组织内脂肪沉积的作用仍有待研究。我们进行这项研究是为了直接定量和定位十二指肠组织内的壁内脂肪沉积,并确定其与肥胖的关系。
从年龄较大的(21.2±1.3 岁,19.5±3.1kg,n=39)雌性狒狒(Papio sp.)中收集十二指肠组织。空腹采集血液进行代谢谱分析,并测量腹围(AC)。在尸检时,在主要十二指肠乳头处采集组织样本:一个完整的横截面用于苏木精和伊红染色,并进行评估;第二个完整的横截面用于直接化学脂质分析,计算十二指肠脂肪含量的百分比。
直接组织定量获得的十二指肠脂肪含量显示出相当大的可变性(11.95±6.93%),与 AC(r=0.60,p<0.001)、体重(r=0.38,p=0.02)、瘦素(r=0.63,p<0.001)、脂联素(r=-0.32,p<0.05)和甘油三酯(r=0.41,p=0.01)呈正相关。调整体重和腹围后,瘦素与十二指肠脂肪含量之间的关系仍然存在。在所有动物的十二指肠切片中都发现了壁内脂肪细胞,并定位于黏膜下层。与组织脂肪含量的变化一致,黏膜下层脂肪细胞不均匀地分布在大小不一的簇中。肥胖动物的十二指肠脂肪细胞比瘦素动物的更大(106.9 比 66.7µm,p=0.02)。
在狒狒中,十二指肠壁内脂肪堆积与肥胖和肥胖相关的循环生物标志物密切相关。十二指肠组织脂肪代表了异位脂肪沉积的一个新的、潜在的代谢活跃部位。