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Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes

Artikel i vetenskaplig tidskrift
Författare A. Mardinoglu
Silvia Gogg
L. A. Lotta
A. Stancakova
Annika Nerstedt
Jan Borén
M. Bluher
E. Ferrannini
C. Langenberg
N. J. Wareham
M. Laakso
Ulf Smith
Publicerad i Ebiomedicine
Volym 27
Sidor 151-155
ISSN 2352-3964
Publiceringsår 2018
Publicerad vid Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor 151-155
Språk en
Länkar dx.doi.org/10.1016/j.ebiom.2017.12....
Ämnesord 3-Hydroxyisobutyric acid (3-HIB), Branched-chain amino acids (BCAAs), T2D, Insulin resistance, Insulin, insulin sensitivity, glucose-tolerance, cardiovascular-disease, metabolic signature, mannose levels, resistance, obesity, risk, General & Internal Medicine, Research & Experimental Medicine
Ämneskategorier Klinisk medicin

Sammanfattning

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.

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