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

Fenofibrate increases very-long-chain sphingolipids and improves blood glucose homeostasis in NOD mice

Research output: Contribution to journalJournal articleResearchpeer-review

  1. The Incidence of Free Peritoneal Tumor Cells before and after Neoadjuvant Chemotherapy in Gastroesophageal Junction Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. PPARs and the development of Type 1 Diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Pitfalls of histopathological evaluation of EUS guided microbiopsies from pancreatic cystic neoplasms

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. L-serine: a neglected amino acid with a potential therapeutic role in diabetes

    Research output: Contribution to journalReviewResearchpeer-review

View graph of relations

AIMS/HYPOTHESIS: Sphingolipid metabolism regulates beta cell biology and inflammation and is abnormal at the onset of type 1 diabetes. Fenofibrate, a regulator of sphingolipid metabolism, is known to prevent diabetes in NOD mice. Here, we aimed to investigate the effects of fenofibrate on the pancreatic lipidome, pancreas morphology, pancreatic sympathetic nerves and blood glucose homeostasis in NOD mice.

METHODS: We treated female NOD mice with fenofibrate from 3 weeks of age. The pancreatic lipidome was analysed using MS. Analysis of pancreas and islet volume was performed by stereology. Islet sympathetic nerve fibre volume was evaluated using tyrosine hydroxylase staining. The effect on blood glucose homeostasis was assessed by measuring non-fasting blood glucose from age 12 to 30 weeks. Furthermore, we measured glucose tolerance, fasting insulin and glucagon levels, and insulin tolerance.

RESULTS: We found that fenofibrate selectively increases the amount of very-long-chain sphingolipids in the pancreas of NOD mice. In addition, we found that fenofibrate causes a remodelling of the pancreatic lipidome with an increased amount of lysoglycerophospholipids. Fenofibrate did not affect islet or pancreas volume, but led to a higher volume of islet sympathetic nerve fibres and tyrosine hydroxylase-positive cells. Fenofibrate-treated NOD mice had a more stable blood glucose, which was associated with reduced non-fasting and increased fasting blood glucose. Furthermore, fenofibrate improved glucose tolerance, reduced fasting glucagon levels and prevented fasting hyperinsulinaemia.

CONCLUSIONS/INTERPRETATION: These data indicate that fenofibrate alters the pancreatic lipidome to a more anti-inflammatory and anti-apoptotic state. The beneficial effects on islet sympathetic nerve fibres and blood glucose homeostasis indicate that fenofibrate could be used as a therapeutic approach to improve blood glucose homeostasis and prevent diabetes-associated pathologies.

Original languageEnglish
Issue number12
Pages (from-to)2262-2272
Number of pages11
Publication statusPublished - Dec 2019

ID: 58996873