Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes
Artikel i vetenskaplig tidskrift, 2018
Branched-chain amino acids (BCAAs) metabolite, 3-Hydroxyisobutyric acid (3-HIB) has been identified as a secreted mediator of endothelial cell fatty acid transport and insulin resistance (IR) using animal models. To identify if 3-HIB is a marker of human IR and future risk of developing Type 2 diabetes (T2D), we measured plasma levels of 3-HIB and associated metabolites in around 10,000 extensively phenotyped individuals. The levels of 3-HIB were increased in obesity but not robustly associated with degree of IR after adjusting for BMI. Nevertheless, also after adjusting for obesity and plasma BCAA, 3-HIB levels were associated with future risk of incident T2D. We also examined the effect of 3-HIB on fatty acid uptake in human cells and found that both HUVEC and human cardiac endothelial cells respond to 3-HIB whereas human adipose tissue-derived endothelial cells do not respond to 3-HIB. In conclusion, we found that increased plasma level of 3-HIB is a marker of future risk of T2D and 3-HIB may be important for the regulation of metabolic flexibility in heart and muscles.
3-Hydroxyisobutyric acid (3-HIB)
Insulin resistance
T2D
Branched-chain amino acids (BCAAs)
Insulin secretion
Författare
Adil Mardinoglu
Chalmers, Biologi och bioteknik, Systembiologi
Kungliga Tekniska Högskolan (KTH)
Silvia Gogg
Göteborgs universitet
Luca A. Lotta
University of Cambridge
Annika Nerstedt
Göteborgs universitet
Jan Boren
Göteborgs universitet
Matthias Blueher
Universität Leipzig
Ele Ferrannini
Consiglio Nazionale delle Ricerche (CNR)
Claudia Langenberg
University of Cambridge
Nicholas J. Wareham
University of Cambridge
Markku Laakso
Itä-Suomen Yliopisto
Ulf Smith
Göteborgs universitet
EBioMedicine
2352-3964 (eISSN)
Vol. 27 151-155Ämneskategorier (SSIF 2011)
Endokrinologi och diabetes
Annan klinisk medicin
Cell- och molekylärbiologi
DOI
10.1016/j.ebiom.2017.12.008
PubMed
29246479