title: Impact of murine intestinal apolipoprotein A-IV expression on regional lipid absorption, gene expression, and growth.
abstract: Apolipoprotein A-IV (apoA-IV) is synthesized by intestinal enterocytes during lipid absorption and secreted into lymph on the surface of nascent chylomicrons. A compelling body of evidence supports a central role of apoA-IV in facilitating intestinal lipid absorption and in regulating satiety, yet a longstanding conundrum is that no abnormalities in fat absorption, feeding behavior, or weight gain were observed in chow-fed apoA-IV knockout (A4KO) mice. Herein we reevaluated the impact of apoA-IV expression in C57BL6 and A4KO mice fed a high-fat diet. Fat balance and lymph cannulation studies found no effect of intestinal apoA-IV gene expression on the efficiency of fatty acid absorption, but gut sac transport studies revealed that apoA-IV differentially modulates lipid transport and the number and size of secreted triglyceride-rich lipoproteins in different anatomic regions of the small bowel. ApoA-IV gene deletion increased expression of other genes involved in chylomicron assembly, impaired the ability of A4KO mice to gain weight and increase adipose tissue mass, and increased the distal gut hormone response to a high-fat diet. Together these findings suggest that apoA-IV may play a unique role in integrating feeding behavior, intestinal lipid absorption, and energy storage.
authors.affiliation: Departments of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Trang
authors.initials: T
authors.lastname: Simon
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Cook
authors.forename: Anuradha
authors.initials: A
authors.lastname: Rao
authors.forename: Richard B
authors.initials: RB
authors.lastname: Weinberg
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D002404:Catheterization; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating / Q000235:genetics; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D048788:Growth and Development / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics*; D042601:Lymphatic Vessels / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D019894:Peptide YY / Q000097:blood; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001054:Apolipoproteins A; D004041:Dietary Fats; D014280:Triglycerides; C022205:apolipoprotein A-IV; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1