An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption

Jahangir Iqbal, Xiaosong Li, Benny Hung Junn Chang, Lawrence Chan, Gary J. Schwartz, Streamson C. Chua, Jr., M. Mahmood Hussain

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Fat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat storage and metabolism. Our aim was to identify the role of leptin signaling in MTP regulation and lipid absorption using several mouse models deficient in leptin receptor (LEPR) signaling and downstream effectors. Mice with spontaneous LEPR B mutations or targeted ablation of LEPR B in proopiomelanocortin (POMC) or agouti gene related peptide (AGRP) expressing cells had increased triglyceride in plasma, liver, and intestine. Furthermore, melanocortin 4 receptor (MC4R) knockout mice expressed a similar triglyceride phenotype, suggesting that leptin might regulate intestinal MTP expression through the melanocortin pathway. Mechanistic studies revealed that the accumulation of triglyceride in the intestine might be secondary to decreased expression of MTP and lipid absorption in these mice. Surgical and chemical blockade of vagal efferent outflow to the intestine in wild-type mice failed to alter the triglyceride phenotype, demonstrating that central neural control mechanisms were likely not involved in the observed regulation of intestinal MTP. Instead, we found that enterocytes express LEPR, POMC, AGRP, and MC4R. We propose that a peripheral, local gut signaling mechanism involving LEPR B and MC4R regulates intestinal MTP and controls intestinal lipid absorption.

Original languageEnglish (US)
Pages (from-to)1929-1942
Number of pages14
JournalJournal of Lipid Research
Volume51
Issue number7
DOIs
StatePublished - Jul 1 2010

Fingerprint

Melanocortins
Leptin Receptors
Leptin
Receptor, Melanocortin, Type 4
Lipids
Intestines
Triglycerides
Pro-Opiomelanocortin
Tissue
Liver
Genes
Fats
Phenotype
Peptides
Enterocytes
Intestinal Absorption
Apolipoproteins B
Ablation
Metabolism
Knockout Mice

Keywords

  • AGRP
  • ApoB
  • Fat absorption
  • Leptin receptor
  • MTP
  • POMC

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology
  • Medicine(all)

Cite this

An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption. / Iqbal, Jahangir; Li, Xiaosong; Chang, Benny Hung Junn; Chan, Lawrence; Schwartz, Gary J.; Chua, Jr., Streamson C.; Hussain, M. Mahmood.

In: Journal of Lipid Research, Vol. 51, No. 7, 01.07.2010, p. 1929-1942.

Research output: Contribution to journalArticle

Iqbal, Jahangir ; Li, Xiaosong ; Chang, Benny Hung Junn ; Chan, Lawrence ; Schwartz, Gary J. ; Chua, Jr., Streamson C. ; Hussain, M. Mahmood. / An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption. In: Journal of Lipid Research. 2010 ; Vol. 51, No. 7. pp. 1929-1942.
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