Enhanced Gastrointestinal Expression of Cytosolic Malic Enzyme (ME1) Induces Intestinal and Liver Lipogenic Gene Expression and Intestinal Cell Proliferation in Mice
| العنوان: | Enhanced Gastrointestinal Expression of Cytosolic Malic Enzyme (ME1) Induces Intestinal and Liver Lipogenic Gene Expression and Intestinal Cell Proliferation in Mice |
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| المؤلفون: | Trang Van, Charles P. Mercado, Patricia A. Wight, Rosalia C. M. Simmen, Frank A. Simmen, John Mark P. Pabona, Charles M. Quick, Hamdan Hamdan, Adam R. Brown, Ahmed Al-Dwairi |
| المصدر: | PLoS ONE PLoS ONE, Vol 9, Iss 11, p e113058 (2014) |
| بيانات النشر: | Public Library of Science, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, Physiology, medicine.medical_treatment, Digestive Physiology, lcsh:Medicine, Adipose tissue, Biochemistry, Fats, Immunoenzyme Techniques, Mice, Cytosol, Malate Dehydrogenase, Intestinal Mucosa, lcsh:Science, Cells, Cultured, Adiposity, 2. Zero hunger, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Fatty Acids, Lipids, Lipid Profiles, Intestines, medicine.anatomical_structure, Cholesterol, Liver, Lipid digestion, Research Article, Nutrient and Storage Proteins, medicine.medical_specialty, Transgene, Lipoproteins, Malic enzyme, Mice, Transgenic, Biology, Diet, High-Fat, Real-Time Polymerase Chain Reaction, Gastrointestinal epithelium, Internal medicine, Glucose Intolerance, medicine, Animals, RNA, Messenger, Nutrition, Cell Proliferation, Endocrine Physiology, Insulin, Lipogenesis, lcsh:R, Biology and Life Sciences, Proteins, Nutrients, Lipid Metabolism, Small intestine, IRS1, Diet, Rats, Gastrointestinal Tract, Endocrinology, Metabolism, Gene Expression Regulation, lcsh:Q, Insulin Resistance, Energy Metabolism |
| الوصف: | The small intestine participates in lipid digestion, metabolism and transport. Cytosolic malic enzyme 1 (ME1) is an enzyme that generates NADPH used in fatty acid and cholesterol biosynthesis. Previous work has correlated liver and adipose ME1 expression with susceptibility to obesity and diabetes; however, the contributions of intestine-expressed ME1 to these conditions are unknown. We generated transgenic (Tg) mice expressing rat ME1 in the gastrointestinal epithelium under the control of the murine villin1 promoter/enhancer. Levels of intestinal ME1 protein (endogenous plus transgene) were greater in Tg than wildtype (WT) littermates. Effects of elevated intestinal ME1 on body weight, circulating insulin, select adipocytokines, blood glucose, and metabolism-related genes were examined. Male Tg mice fed a high-fat (HF) diet gained significantly more body weight than WT male littermates and had heavier livers. ME1-Tg mice had deeper intestinal and colon crypts, a greater intestinal 5-bromodeoxyuridine labeling index, and increased expression of intestinal lipogenic (Fasn, Srebf1) and cholesterol biosynthetic (Hmgcsr, Hmgcs1), genes. The livers from HF diet-fed Tg mice also exhibited an induction of cholesterol and lipogenic pathway genes and altered measures (Irs1, Irs2, Prkce) of insulin sensitivity. Results indicate that gastrointestinal ME1 via its influence on intestinal epithelial proliferation, and lipogenic and cholesterologenic genes may concomitantly impact signaling in liver to modify this tissue's metabolic state. Our work highlights a new mouse model to address the role of intestine-expressed ME1 in whole body metabolism, hepatomegaly, and crypt cell proliferation. Intestinal ME1 may thus constitute a therapeutic target to reduce obesity-associated pathologies. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc6429400167ad673d8dcbf9a352a6b5Test http://europepmc.org/articles/PMC4234650Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dc6429400167ad673d8dcbf9a352a6b5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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