Individual and combined effects of GIP and xenin on differentiation, glucose uptake and lipolysis in 3T3-L1 adipocytes

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Abstract

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP), released postprandially from K-cells, has established actions on adipocytes and lipid metabolism. In addition, xenin, a related peptide hormone also secreted from K-cells after a meal, has postulated effects on energy regulation and lipid turnover. The current study has probed direct individual and combined effects of GIP and xenin on adipocyte function in 3T3-L1 adipocytes, using enzyme-resistant peptide analogues, (D-Ala2)GIP and xenin-25-Gln, and knockdown (KD) of receptors for both peptides. (D-Ala2)GIP stimulated adipocyte differentiation and lipid accumulation in 3T3-L1 adipocytes over 96h, with xenin-25-Gln evoking similar effects. Combined treatment significantly countered these individual adipogenic effects. Individual receptor KD impaired lipid accumulation and adipocyte differentiation, with combined receptor KD preventing differentiation. (D-Ala2)GIP and xenin-25-Gln increased glycerol release from 3T3-L1 adipocytes, but this lipolytic effect was significantly less apparent with combined treatment. Key adipogenic and lipolytic genes were upregulated by (D-Ala2)GIP or xenin-25-Gln, but not by dual peptide culture. Similarly, both (D-Ala2)GIP and xenin-25-Gln stimulated insulin-induced glucose uptake in 3T3-L1 adipocytes, but this effect was annulled by dual treatment. In conclusion, GIP and xenin possess direct, comparable, lipogenic and lipolytic actions in 3T3-L1 adipocytes. However, effects on lipid metabolism are significantly diminished by combined administration.
Original languageEnglish
Pages (from-to)1293-1303
Number of pages11
JournalBiological Chemistry
Volume401
Issue number11
Early online date26 Aug 2020
DOIs
Publication statusPublished - 25 Oct 2020

Bibliographical note

Funding Information:
These studies were supported by research grants from Invest Northern Ireland Proof of Concept funding, European Foundation for the Study of Diabetes and Department for the Economy, Northern Ireland.

Publisher Copyright:
© 2020 De Gruyter. All rights reserved.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • 3T3-L1 adipocytes
  • differentiation
  • glucose uptake
  • glucose-dependent insulinotropic polypeptide (GIP)
  • lipid metabolism
  • xenin

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