Supplementary choline attenuates olive oil lipid emulsion‐induced enterocyte apoptosis through suppression of CELF1/AIF pathway

• Published in: Journal of cellular and molecular medicine 2018-03, Vol.22 (3), p.1562-1573
• Main Authors: Yan, Jun‐Kai, Zhu, Jie, Gong, Zi‐Zhen, Wen, Jie, Xiao, Yong‐Tao, Zhang, Tian, Cai, Wei
• Format: Article
• Language: English
• Subjects: AIF; Animals; apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Apoptosis Inducing Factor - genetics; Apoptosis Inducing Factor - metabolism; Atrophy - chemically induced; Atrophy - genetics; Atrophy - physiopathology; Atrophy - prevention & control; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Caco-2 Cells; Caco‐2; Caspase 3 - genetics; Caspase 3 - metabolism; CELF1; CELF1 Protein - genetics; CELF1 Protein - metabolism; choline; Choline - administration & dosage; Choline Deficiency - genetics; Choline Deficiency - physiopathology; Choline Deficiency - prevention & control; Disease Models, Animal; Emulsions; Enterocytes - drug effects; Enterocytes - metabolism; Enterocytes - pathology; Gene Expression Regulation; Humans; intestinal atrophy; Intestines - drug effects; Intestines - physiopathology; Male; Mitochondria - drug effects; Mitochondria - metabolism; Olive Oil - administration & dosage; Olive Oil - adverse effects; olive oil lipid emulsion; Original; Parenteral Nutrition, Total - adverse effects; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; total parenteral nutrition
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13430

Enterocyte apoptosis induced by lipid emulsions is a key cause of intestinal atrophy under total parenteral nutrition (TPN) support, and our previous work demonstrated that olive oil lipid emulsion (OOLE) could induce enterocyte apoptosis via CUGBP, Elav‐like family member 1 (CELF1)/ apoptosis‐inducing factor (AIF) pathway. As TPN‐associated complications are partially related to choline deficiency, we aimed to address whether choline supplementation could attenuate OOLE‐induced enterocyte apoptosis. Herein we present evidence that supplementary choline exhibits protective effect against OOLE‐induced enterocyte apoptosis both in vivo and in vitro. In a rat model of TPN, substantial reduction in apoptotic rate along with decreased expression of CELF1 was observed when supplementary choline was added to OOLE. In cultured Caco‐2 cells, supplementary choline attenuated OOLE‐induced apoptosis and mitochondria dysfunction by suppressing CELF1/AIF pathway. Compared to OOLE alone, the expression of CELF1 and AIF was significantly decreased by supplementary choline, whereas the expression of Bcl‐2 was evidently increased. No obvious alterations were observed in Bax expression and caspase‐3 activation. Mechanistically, supplementary choline repressed the expression of CELF1 by increasing the recruitment of CELF1 mRNA to processing bodies, thus resulting in suppression of its protein translation. Taken together, our data suggest that supplementary choline exhibits effective protection against OOLE‐induced enterocyte apoptosis, and thus, it has the potential to be used for the prevention and treatment of TPN‐induced intestinal atrophy.