Genetic Nicotinamide N-Methyltransferase (Nnmt) Deficiency in Male Mice Improves Insulin Sensitivity in Diet-Induced Obesity but Does Not Affect Glucose Tolerance
| العنوان: | Genetic Nicotinamide N-Methyltransferase (Nnmt) Deficiency in Male Mice Improves Insulin Sensitivity in Diet-Induced Obesity but Does Not Affect Glucose Tolerance |
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| المؤلفون: | Ralf Elvert, Maria Brachs, Kerstin Jahn-Hofmann, Sebastian Brachs, Felix Bärenz, Anja Pfenninger, Joachim Spranger, Daniel Margerie, James Polack, Aimo Kannt, Knut Mai |
| المصدر: | Diabetes. 68:527-542 |
| بيانات النشر: | American Diabetes Association, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Nicotinamide, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, Adipose tissue, 030209 endocrinology & metabolism, Nicotinamide N-methyltransferase, Biology, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Endocrinology, Insulin resistance, chemistry, Weight loss, Internal medicine, Blood plasma, Internal Medicine, medicine, medicine.symptom, Weight gain |
| الوصف: | Antisense oligonucleotide knockdown (ASO-KD) of nicotinamide N-methyltransferase (NNMT) in high-fat diet (HFD)–fed mice has been reported to reduce weight gain and plasma insulin levels and to improve glucose tolerance. Using NNMT-ASO-KD or NNMT knockout mice (NNMT−/−), we tested the hypothesis that Nnmt deletion protects against diet-induced obesity and its metabolic consequences in males and females on obesity-inducing diets. We also examined samples from a human weight reduction (WR) study for adipose NNMT (aNNMT) expression and plasma 1-methylnicotinamide (MNAM) levels. In Western diet (WD)–fed female mice, NNMT-ASO-KD reduced body weight, fat mass, and insulin level and improved glucose tolerance. Although NNMT−/− mice fed a standard diet had no obvious phenotype, NNMT−/− males fed an HFD showed strongly improved insulin sensitivity (IS). Furthermore, NNMT−/− females fed a WD showed reduced weight gain, less fat, and lower insulin levels. However, no improved glucose tolerance was observed in NNMT−/− mice. Although NNMT expression in human fat biopsy samples increased during WR, corresponding plasma MNAM levels significantly declined, suggesting that other mechanisms besides aNNMT expression modulate circulating MNAM levels during WR. In summary, upon NNMT deletion or knockdown in males and females fed different obesity-inducing diets, we observed sex- and diet-specific differences in body composition, weight, and glucose tolerance and estimates of IS. |
| تدمد: | 1939-327X 0012-1797 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::39f832a174ac69275e830a769b40f6a4 https://doi.org/10.2337/db18-0780 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........39f832a174ac69275e830a769b40f6a4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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