Leptin regulates gallbladder genes related to absorption and secretion

Deborah A. Swartz-Basile, Debao Lu, David P. Basile, Shannon J. Graewin, Hayder Al-Azzawi, James M. Kiely, Abhishek Mathur, Kyle Yancey, Henry A. Pitt

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Dysregulation of gallbladder ion and water absorption and/or secretion has been linked to cholesterol crystal and gallstone formation. We have recently demonstrated that obese, leptin-deficient (Lepob) mice have enlarged gallbladder volumes and decreased gallbladder contractility and that leptin administration to these mice normalizes gallbladder function. However, the effect of leptin on gallbladder absorption/secretion is not known. Therefore, we sought to determine whether leptin would alter the expression of genes involved in water and ion transport across the gallbladder epithelium. Affymetrix oligonucleotide microarrays representing 39,000 transcripts were used to compare gallbladder gene-expression profiles from 12-wk-old control salinetreated Lepob and from leptin-treated Lepob female mice. Leptin administration to Lepob mice decreased gallbladder volume, bile sodium concentration, and pH. Leptin repletion upregulated the expression of aquaporin 1 water channel by 1.3-fold and downregulated aquaporin 4 by 2.3-fold. A number of genes involved in sodium transport were also influenced by leptin replacement. Epithelial sodium channel-α and sodium hydrogen exchangers 1 and 3 were moderately downregulated by 2.0-, 1.6-, and 1.3-fold, respectively. Carbonic anhydrase-IV, which plays a role in the acidification of bile, was upregulated 3.7-fold. In addition, a number of inflammatory cytokines that are known to influence gallbladder epithelial cell absorption and secretion were upregulated. Thus leptin, an adipocyte-derived cytokine involved with satiety and energy balance, influences gallbladder bile volume, sodium, and pH as well as multiple inflammatory cytokine genes and genes related to water, sodium, chloride, and bicarbonate transport.

Original languageEnglish (US)
Pages (from-to)G84-G90
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume293
Issue number1
DOIs
StatePublished - Jul 2007

Keywords

  • Cytokines
  • Ion transport
  • Leptin
  • Obesity

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

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