Reduced Gut Acidity Induces an Obese-Like Phenotype in Drosophila melanogaster and in MiceReport as inadecuate




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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.



Author: Wei-Sheng Lin , Cheng-Wen Huang , You-Sheng Song , Jui-Hung Yen, Ping-Chang Kuo, Sheng-Rong Yeh, Hung-Yu Lin, Tsai-Feng Fu, Ming-

Source: http://plos.srce.hr/



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