Gastroenterology
Volume 137, Issue 3 , Pages 997-1005.e4, September 2009

Glucagon-Like Peptide-2 Increases Intestinal Lipid Absorption and Chylomicron Production via CD36

  • Joanne Hsieh

      Affiliations

    • Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
    • Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
    • ,
  • Christine Longuet

      Affiliations

    • Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    • ,
  • Adriano Maida

      Affiliations

    • Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    • ,
  • Jasmine Bahrami

      Affiliations

    • Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    • ,
  • Elaine Xu

      Affiliations

    • Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
    • ,
  • Christopher L. Baker

      Affiliations

    • Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
    • ,
  • Patricia L. Brubaker

      Affiliations

    • Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    • Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    • ,
  • Daniel J. Drucker

      Affiliations

    • Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    • ,
  • Khosrow Adeli

      Affiliations

    • Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
    • Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
    • Corresponding Author InformationReprint requests Address requests for reprints to: Khosrow Adeli, MD, Division of Clinical Biochemistry, DPLM, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Atrium Room 3652, Toronto, Ontario, Canada, M5G 1X8. fax: (416) 813-6257

Received 17 September 2008; accepted 20 May 2009. published online 01 June 2009.

Background & Aims

Excessive postprandial lipemia is a prevalent condition that results from intestinal oversecretion of apolipoprotein B48 (apoB48)-containing lipoproteins. Glucagon-like peptide-2 (GLP-2) is a gastrointestinal-derived intestinotropic hormone that links nutrient absorption to intestinal structure and function. We investigated the effects of GLP-2 on intestinal lipid absorption and lipoprotein production.

Methods

Intestinal lipid absorption and chylomicron production were quantified in hamsters, wild-type mice, and Cd36−/− mice infused with exogenous GLP-2. Newly synthesized apoB48 was metabolically labelled in primary hamster jejunal fragments. Fatty acid absorption was measured, and putative fatty acid transporters were assessed by immunoblotting.

Results

Human GLP-2 increased secretion of the triglyceride (TG)-rich lipoprotein (TRL)-apoB48 following oral administration of olive oil to hamsters; TRL and cholesterol mass each increased 3-fold. Fast protein liquid chromatography profiling indicated that GLP-2 stimulated secretion of chylomicron/very low-density lipoprotein-sized particles. Moreover, GLP-2 directly stimulated apoB48 secretion in jejunal fragments cultured ex vivo, increased expression of fully glycosylated cluster of differentiation 36/fatty acid translocase (CD36), and induced intestinal absorption of [3H]triolein. The ability of GLP-2 to increase intestinal lipoprotein production was lost in Cd36−/− mice.

Conclusions

GLP-2 stimulates intestinal apoB48-containing lipoprotein secretion, possibly through increased lipid uptake, via a pathway that requires CD36. These findings suggest that GLP-2 represents a nutrient-dependent signal that regulates intestinal lipid absorption and the assembly and secretion of TRLs from intestinal enterocytes.

Abbreviations used in this paper: apoB48, apolipoprotein B48, CM, chylomicron, CD36, cluster of differentiation 36/fatty acid translocase, FPLC, fast protein liquid chromatography, FATP4, fatty acid transporter protein 4, GLP-2, glucagon-like peptide-2, HDL, high-density lipoprotein, LDL, low-density lipoprotein, MTP, microsomal triglyceride transfer protein, TG, triglyceride, TRL, triglyceride-rich lipoprotein, VLDL, very low-density lipoprotein

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 Conflicts of interest The authors disclose the following: Daniel J. Drucker (Dr Drucker is a party to a licensing agreement among the University of Toronto, the University Health Network, and NPS Pharmaceuticals Inc in regard to the clinical development of GLP-2). The remaining authors disclose no conflicts.

 Funding Supported by CIHR grant MOP-53093 (to K.A.) and CIHR grant MOP-14799 (to D.J.D.). J.H. is supported by the NSERC CGS M, Restracomp, and CIHR CGS D fellowships.

PII: S0016-5085(09)00868-3

doi:10.1053/j.gastro.2009.05.051

Refers to article:

  • Intestinal Lipid Absorption, GLP-2, and CD36: Still More Mysteries to Moving Fat , 29 July 2009

    Elizabeth P. Newberry, Nicholas O. Davidson
    Gastroenterology September 2009 (Vol. 137, Issue 3, Pages 775-778)

Gastroenterology
Volume 137, Issue 3 , Pages 997-1005.e4, September 2009

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