Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes
Journal article, 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.
Insulin secretion
Insulin resistance
3-Hydroxyisobutyric acid (3-HIB)
Branched-chain amino acids (BCAAs)
T2D
Author
Adil Mardinoglu
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Royal Institute of Technology (KTH)
Silvia Gogg
University of Gothenburg
Luca A. Lotta
University of Cambridge
Annika Nerstedt
University of Gothenburg
Jan Boren
University of Gothenburg
Matthias Blueher
Leipzig University
Ele Ferrannini
CNR Inst Clin Physiol
Claudia Langenberg
University of Cambridge
Nicholas J. Wareham
University of Cambridge
Markku Laakso
University of Eastern Finland
Ulf Smith
University of Gothenburg
EBioMedicine
2352-3964 (eISSN)
Vol. 27 151-155Subject Categories
Endocrinology and Diabetes
Other Clinical Medicine
Cell and Molecular Biology
DOI
10.1016/j.ebiom.2017.12.008
PubMed
29246479