Over-expression of Follistatin-like 3 attenuates fat accumulation and improves insulin sensitivity in mice
| Autor: | Claus Brandt, Julie Gehl, Pernille Hojman, Jakob Bondo Hansen, Thomas Mandrup-Poulsen, Pia Galle, Rasmus Hvass Hansen, Bente Klarlund Pedersen, Caroline Holkmann Olsen |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Follistatin-Related Proteins Endocrinology Diabetes and Metabolism medicine.medical_treatment Subcutaneous Fat Myostatin Diet High-Fat Muscle Development Glucagon Islets of Langerhans Random Allocation Endocrinology Insulin resistance Downregulation and upregulation Internal medicine Glucose Intolerance medicine Animals Insulin Muscle Skeletal Adiposity geography geography.geographical_feature_category biology Proteins Islet medicine.disease Recombinant Proteins Insulin oscillation Activins Up-Regulation Mice Inbred C57BL Liver biology.protein Female Insulin Resistance Follistatin Signal Transduction |
| Zdroj: | Metabolism: clinical and experimental. 64(2) |
| ISSN: | 1532-8600 |
| Popis: | Objective Follistatin-like 3 (fstl3), a natural inhibitor of members of the TGF-β family, increases during resistance training in human plasma. Fstl3 primarily binds myostatin and activin A, and thereby inhibits their functions. We hypothesize that blocking myostatin and activin A signalling through systemic fstl3 over-expression protects against diet-induced obesity and insulin resistance. Methods Fstl3 was over-expressed by DNA electrotransfer in tibialis anterior, quadriceps and gastrocnemius muscles in female C57BL/C mice, and the mice were subsequently randomized to chow or high-fat feeding. Body weight, food intake, fat accumulation by MR scanning, and glucose, insulin and glucagon tolerance were evaluated, as was the response in body weight and metabolic parameters to 24 h fasting. Effects of fstl3 on pancreatic insulin and glucagon content, and pancreatic islet morphology were determined. Results Fstl3 over-expression reduced fat accumulation during high-fat feeding by 16%, and liver fat by 50%, as determined by MRI. No changes in body weight were observed, while the weight of the transfected muscles increased by 10%. No transcriptional changes were found in the subcutaneous adipose tissue. Fstl3 mice displayed improved insulin sensitivity and muscle insulin signalling. In contrast, glucose tolerance was impaired in high-fat fed fstl3 mice, which was explained by increased hepatic glucagon sensitivity and glucose output, as well as a decrease in the pancreatic insulin/glucagon ratio. Accordingly, fstl3 transfection improved counter-regulation to 24 h fasting. Conclusion Fstl3 over-expression regulates insulin and glucagon sensitivities through increased muscular insulin action, as well as increased hepatic glucagon sensitivity and pancreatic glucagon content. |
| Databáze: | OpenAIRE |
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