TY - JOUR
T1 - Individual and combined effects of GIP and xenin on differentiation, glucose uptake and lipolysis in 3T3-L1 adipocytes
AU - English, Andrew
AU - Craig, Sarah
AU - Flatt, PR
AU - Irwin, Nigel
N1 - 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 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/25
Y1 - 2020/10/25
N2 - 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.
AB - 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.
KW - 3T3-L1 adipocytes
KW - differentiation
KW - glucose uptake
KW - glucose-dependent insulinotropic polypeptide (GIP)
KW - lipid metabolism
KW - xenin
UR - http://www.scopus.com/inward/record.url?scp=85092292402&partnerID=8YFLogxK
U2 - 10.1515/hsz-2020-0195
DO - 10.1515/hsz-2020-0195
M3 - Article
C2 - 32769216
VL - 401
SP - 1293
EP - 1303
JO - Biological Chemistry
JF - Biological Chemistry
SN - 1431-6730
IS - 11
ER -