Browsing by Author "Lin, Wei-Sheng"

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    Ludwigia octovalvis extract improves glycemic control and memory performance in diabetic mice
    (Elsevier, 2017-07) Lin, Wei-Sheng; Lo, Jung-Hsin; Yang, Jo-Hsuan; Wang, Hao-Wei; Fan, Shou-Zen; Yen, Jui-Hung; Wang, Pei-Yu; Department of Microbiology and Immunology, IU School of Medicine
    Ethnopharmacological relevance Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) extracts have historically been consumed as a healthful drink for treating various conditions, including edema, nephritis, hypotension and diabetes. Aim of the study We have previously shown that Ludwigia octovalvis extract (LOE) can significantly extend lifespan and improve age-related memory deficits in Drosophila melanogaster through activating AMP-activated protein kinase (AMPK). Since AMPK has become a critical target for treating diabetes, we herein investigate the anti-hyperglycemic potential of LOE. Materials and methods Differentiated C2C12 muscle cells, HepG2 hepatocellular cells, streptozotocin (STZ)-induced diabetic mice and high fat diet (HFD)-induced diabetic mice were used to investigate the anti-hyperglycemic potential of LOE. The open field test and novel object recognition test were used to evaluate spontaneous motor activity and memory performance of HFD-induced diabetic mice. Results In differentiated C2C12 muscle cells and HepG2 hepatocellular cells, treatments with LOE and its active component (β-sitosterol) induced significant AMPK phosphorylation. LOE also enhanced uptake of a fluorescent glucose derivative (2-NBDG) and inhibited glucose production in these cells. The beneficial effects of LOE were completely abolished when an AMPK inhibitor, dorsomorphin, was added to the culture system, suggesting that LOE requires AMPK activation for its action in vitro. In streptozotocin (STZ)-induced diabetic mice, we found that both LOE and β-sitosterol induced an anti-hyperglycemic effect comparable to that of metformin, a drug that is commonly prescribed to treat diabetes. Moreover, LOE also improved glycemic control and memory performance of mice fed a HFD. Conclusions These results indicate that LOE is a potent anti-diabetic intervention that may have potential for future clinical applications.
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    Reduced Gut Acidity Induces an Obese-Like Phenotype in Drosophila melanogaster and in Mice
    (PLOS, 2015-10-05) Lin, Wei-Sheng; Huang, Cheng-Wen; Yen, Jui-Hung; Kuo, Ping- Chang; Yeh, Sheng-Rong; Lin, Hung-Yu; Fu, Tsai-Feng; Wu, Ming-Shiang; Wang, Horng- Dar; Wang, Pei-Yu; Song, You-Sheng; Department of Microbiology & Immunology, IU School of Medicine
    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.
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    Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement
    (PLOS, 2019-03-18) Teng, Ling-Ling; Lu, Guan-Ling; Chiou, Lih-Chu; Lin, Wei-Sheng; Cheng, Ya-Yun; Hsueh, Tai-En; Huang, Yi-Ching; Hwang, Nai-Hsuan; Yeh, Jin-Wei; Liao, Ruey-Ming; Fan, Shou-Zen; Yen, Jui-Hung; Fu, Tsai-Feng; Tsai, Ting-Fen; Wu, Ming-Shiang; Wang, Pei-Yu; Microbiology and Immunology, School of Medicine
    Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake.