Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital

Over-expression of Follistatin-like 3 attenuates fat accumulation and improves insulin sensitivity in mice

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Lipidome as a predictive tool in progression to type 2 diabetes in Finnish men

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Abnormal levels of adipokines in adolescent offspring of women with type 1 diabetes - Results from the EPICOM study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Imbalance of plasma amino acids, metabolites and lipids in patients with lysinuric protein intolerance (LPI)

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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 24h 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 24h 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.

Original languageEnglish
JournalMetabolism: Clinical and Experimental
Issue number2
Pages (from-to)283-95
Number of pages13
Publication statusPublished - Feb 2015

ID: 44847238