Reduced gut acidity induces an obese-like phenotype in drosophila melanogaster and in mice
Journal
PLoS ONE
Journal Volume
10
Journal Issue
10
Date Issued
2015
Author(s)
Lin W.-S.
Huang C.-W.
Song Y.-S.
Yen J.-H.
Kuo P.-C.
Yeh S.-R.
Lin H.-Y.
Fu T.-F.
Wang H.-D.
Abstract
In order to identify genes involved in stress and metabolic regulation, we carried out a Drosophila P-element-mediated mutagenesis screen for starvation resistance. We isolated a mutant, m2, that showed a 23% increase in survival time under starvation conditions. The P-element insertion was mapped to the region upstream of the vha16-1 gene, which encodes the c subunit of the vacuolar-type H+-ATPase. We found that vha16-1 is highly expressed in the fly midgut, and that m2 mutant flies are hypomorphic for vha16-1 and also exhibit reduced midgut acidity. This deficit is likely to induce altered metabolism and contribute to accelerated aging, since vha16-1 mutant flies are short-lived and display increases in body weight and lipid accumulation. Similar phenotypes were also induced by pharmacological treatment, through feeding normal flies and mice with a carbonic anhydrase inhibitor (acetazolamide) or proton pump inhibitor (PPI, lansoprazole) to suppress gut acid production. Our study may thus provide a useful model for investigating chronic acid suppression in patients.
Publisher
Public Library of Science
Type
journal article