Cover Image

Impaired Detoxification of Trans, Trans-2,4-Decadienal, an Oxidation Product from Omega-6 Fatty Acids, Alters Insulin Signaling, Gluconeogenesis and Promotes Microvascular Disease

Omega-6 fatty acids are the primary polyunsaturated fatty acids in most Western diets, while their role in diabetes remains controversial. Exposure of omega-6 fatty acids to an oxidative environment results in the generation of a highly reactive carbonyl species known as trans, trans-2,4-decadienal...

Full description

Saved in:
Bibliographic Details
Main Authors: Qian, Xin (Author) , Klatt, Stephan (Author) , Bennewitz, Katrin (Author) , Wohlfart, David Philipp (Author) , Lou, Bowen (Author) , Meng, Ye (Author) , Büttner, Michael (Author) , Poschet, Gernot (Author) , Morgenstern, Jakob (Author) , Fleming, Thomas (Author) , Sticht, Carsten (Author) , Haußer-Siller, Ingrid (Author) , Fleming, Ingrid (Author) , Szendrödi, Julia (Author) , Nawroth, Peter Paul (Author) , Kroll, Jens (Author)
Format: Article (Journal)
Language:English
Published: January 26, 2024
In: Advanced science
Year: 2024, Volume: 11, Issue: 4, Pages: 1-17
ISSN:2198-3844
DOI:10.1002/advs.202302325
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/advs.202302325
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202302325
Get full text
Author Notes:Xin Qian, Stephan Klatt, Katrin Bennewitz, David Philipp Wohlfart, Bowen Lou, Ye Meng, Michael Buettner, Gernot Poschet, Jakob Morgenstern, Thomas Fleming, Carsten Sticht, Ingrid Hausser, Ingrid Fleming, Julia Szendroedi, Peter Paul Nawroth, and Jens Kroll
Description
Summary:Omega-6 fatty acids are the primary polyunsaturated fatty acids in most Western diets, while their role in diabetes remains controversial. Exposure of omega-6 fatty acids to an oxidative environment results in the generation of a highly reactive carbonyl species known as trans, trans-2,4-decadienal (tt-DDE). The timely and efficient detoxification of this metabolite, which has actions comparable to other reactive carbonyl species, such as 4-hydroxynonenal, acrolein, acetaldehyde, and methylglyoxal, is essential for disease prevention. However, the detoxification mechanism for tt-DDE remains elusive. In this study, the enzyme Aldh9a1b is identified as having a key role in the detoxification of tt-DDE. Loss of Aldh9a1b increased tt-DDE levels and resulted in an abnormal retinal vasculature and glucose intolerance in aldh9a1b−/− zebrafish. Transcriptomic and metabolomic analyses revealed that tt-DDE and aldh9a1b deficiency in larval and adult zebrafish induced insulin resistance and impaired glucose homeostasis. Moreover, alterations in hyaloid vasculature is induced by aldh9a1b knockout or by tt-DDE treatment can be rescued by the insulin receptor sensitizers metformin and rosiglitazone. Collectively, these results demonstrated that tt-DDE is the substrate of Aldh9a1b which causes microvascular damage and impaired glucose metabolism through insulin resistance.
Item Description:Online verfügbar: 7. Dezember 2023
Gesehen am 29.01.2024
Physical Description:Online Resource
ISSN:2198-3844
DOI:10.1002/advs.202302325

Similar Items