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Leptin action in intestinal cells

N M Morton1, V Emilsson, Y L Liu

  • 1Clore Laboratory, University of Buckingham, Buckingham, MK18 1EG, United Kingdom.

The Journal of Biological Chemistry
|September 25, 1998
PubMed
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Leptin, an adipocyte hormone, activates signaling pathways in the jejunum, suggesting a direct role in lipid handling and potentially contributing to obesity. This study identifies the jejunum as a novel target for leptin action.

Area of Science:

  • Endocrinology
  • Gastroenterology
  • Molecular Biology

Background:

  • Leptin is known to regulate satiety and energy expenditure via hypothalamic pathways.
  • Leptin's in vivo signaling in tissues beyond the hypothalamus remains largely uncharacterized.
  • The role of leptin in gastrointestinal function and metabolism is an area of active investigation.

Purpose of the Study:

  • To investigate leptin receptor expression and signaling in the mouse gastrointestinal tract.
  • To determine if leptin directly influences jejunal function, particularly in lipid handling.
  • To elucidate the role of leptin signaling in the small intestine in the context of obesity.

Main Methods:

  • Reverse transcription-polymerase chain reaction (RT-PCR) to detect leptin receptor (OB-Rb) expression in isolated enterocytes.

Related Experiment Videos

  • In vivo studies involving intravenous leptin injection in wild-type, obese (ob/ob), and diabetic (db/db) mice.
  • Analysis of STAT3 and STAT5 DNA binding activity, immediate-early gene induction (c-fos), and apolipoprotein AIV transcript levels in jejunal tissue.
  • In vitro studies using CACO-2 cells, a human small intestine epithelium model.

    • Main Results:

    • Functional leptin receptor (OB-Rb) expression was detected in the jejunum, specifically in enterocytes.
    • Leptin administration rapidly induced STAT5 DNA binding activity and c-fos expression in the jejunum of wild-type and ob/ob mice, but not in db/db mice.
    • Leptin significantly reduced apolipoprotein AIV transcript levels in the jejunum following a fat load.
    • Leptin-mediated induction of immediate-early genes and STAT3/STAT5 activation was confirmed in CACO-2 cells.

    Conclusions:

    • The jejunum epithelium is a direct target of leptin action, mediated by the OB-Rb receptor.
    • Leptin signaling in the jejunum plays a role in regulating lipid handling, as evidenced by changes in apolipoprotein AIV expression.
    • Leptin deficiency or resistance in the jejunum may contribute to obesity and related metabolic disorders by impacting lipid metabolism.