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Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes
KTH, Centres, Science for Life Laboratory, SciLifeLab.
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 27, p. 151-155Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV , 2018. Vol. 27, p. 151-155
Keywords [en]
3-Hydroxyisobutyric acid (3-HIB), Branched-chain amino acids (BCAAs), T2D, Insulin resistance, Insulin secretion
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:kth:diva-224059DOI: 10.1016/j.ebiom.2017.12.008ISI: 000425875400020PubMedID: 29246479OAI: oai:DiVA.org:kth-224059DiVA, id: diva2:1190975
Note

QC 20180316

Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2018-03-16Bibliographically approved

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Mardinoglu, Adil

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