title: Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.
abstract: Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes.
authors.affiliation: Department Of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America; Institute Of Medicinal Plant Development, Chinese Academy Of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department Of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department Of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America; Department Of Animal And Avian Sciences, University Of Maryland, College Park, Maryland, United States of America.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department Of Animal And Avian Sciences, University Of Maryland, College Park, Maryland, United States of America.
authors.forename: Hongling
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department Of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America.
authors.forename: Freddy
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department Of Biology, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Bingzhong
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department Of Biology, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Hang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department Of Physiology, University Of South Alabama College Of Medicine, Mobile, Alabama, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department Of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America; Department Of Animal And Avian Sciences, University Of Maryland, College Park, Maryland, United States of America.
authors.forename: Liqing
authors.initials: L
authors.lastname: Yu
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006868:Hydrolysis; D007408:Intestinal Absorption / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000473:pathology; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D019518:Postprandial Period; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D014280:Triglycerides; D002784:Cholesterol; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C492986:Abhd5 protein, mouse; D008049:Lipase