Creeping Fat-Derived Free Fatty Acids Induce Hyperplasia of Intestinal Muscularis Propria Muscle Cells: A Novel Link Between Fat and Intestinal Stricture Formation in Crohn's Disease.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Liu Weiwei, Mao Ren, Nga Le Thi Hong, West Gail, Varadharajan Venkateshwari, Banerjee Rakhee, Doyon Genevieve, Mukherjee Pranab, Nguyen Quang Tam, Mulya Anny, Rennison Julie H, Gordon Ilyssa O, Cruise Michael, Hu Shaomin, Czarnecki Doug, Plesec Thomas, Chandra Jyotsna, Banerjee Suhanti, Wang Jie, Massey William J, Goren Idan, Lin Si-Nan, Kurada Satya, Cohen Benjamin L, Qazi Taha, Holubar Stefan D, Lipman Jeremy, Kanters Arielle, Gliniak Christy M, Scherer Philipp E, Chen Min-Hu, Siegmund Britta, Ivanov Andrei I, Fiocchi Claudio, Van Wagoner David R, Brown J Mark, Rieder Florian
Аннотация
METHODS: Free fatty acids (FFAs) in creeping fat or noncreeping mesenteric fat organ cultures were measured via lipidomic mass spectrometry. Primary HIMCs were exposed to FFAs and cell proliferation was assessed. Intracellular FFA metabolism pathways and reactive oxygen species were functionally evaluated. Muscle thickness was investigated in dextran sodium sulfate colitis with small molecule inhibition of FFA transport and a novel fat deletion mouse model.
RESULTS: Subserosal creeping fat is associated with a markedly thickened MP. Experimental deletion of mesenteric fat (FAT-ATTAC [fat apoptosis through targeted activation of caspase 8] mouse) reduced MP thickness. Human creeping fat-conditioned medium strongly up-regulated HIMC proliferation. Creeping fat released higher amounts of 5 long-chain FFAs, including palmitate. Inhibition of HIMC long-chain FFA metabolism or FFA uptake into mitochondria through carnitine palmitoyltransferase-1 reduced the palmitate-induced HIMC proliferation. Blockade of conversion of palmitate into phospholipids reduced HIMC proliferation. Prophylactic inhibition of carnitine palmitoyltransferase-1 in experimental dextran sodium sulfate colitis did not ameliorate inflammation, but reduced MP thickness.
CONCLUSIONS: Creeping fat-released long-chain FFAs induce a selective proliferative response by HIMC. These results point to creeping fat as a novel contributor to stricture formation in Crohn's disease.