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

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

  • EBioMedicine. 2018 Jan:27:151-155. doi: 10.1016/j.ebiom.2017.12.008.
Adil Mardinoglu 1,  Silvia Gogg 2,  Luca A Lotta 3,  Alena Stančáková 4,  Annika Nerstedt 5,  Jan Boren 6,  Matthias Blüher 7,  Ele Ferrannini 8,  Claudia Langenberg 9,  Nicholas J Wareham 10,  Markku Laakso 11,  Ulf Smith 12
Affiliations

Affiliations

  • 1 Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden. Electronic address: adilm@scilifelab.se.
  • 2 Department of Molecular and Clinical Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: silvia.gogg@medic.gu.se.
  • 3 MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. Electronic address: luca.lotta@mrc-epid.cam.ac.uk.
  • 4 Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio University Hospital, Kuopio, Finland. Electronic address: alena.yaluri@uef.fi.
  • 5 Department of Molecular and Clinical Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: annika.nerstedt@gu.se.
  • 6 Department of Molecular and Clinical Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: Jan.Boren@wlab.gu.se.
  • 7 University of Leipzig, Department of Medicine, Leipzig, Germany. Electronic address: Matthias.Blueher@medizin.uni-leipzig.de.
  • 8 CNR Institute of Clinical Physiology, Pisa, Italy. Electronic address: ferranni@ifc.cnr.it.
  • 9 MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. Electronic address: Claudia.Langenberg@mrc-epid.cam.ac.uk.
  • 10 MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. Electronic address: nick.wareham@mrc-epid.cam.ac.uk.
  • 11 Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio University Hospital, Kuopio, Finland. Electronic address: markku.laakso@uef.fi.
  • 12 Department of Molecular and Clinical Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: ulf.smith@medic.gu.se.
PMID: 29246479 DOI: 10.1016/j.ebiom.2017.12.008
Abstract

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.

Keywords

3-Hydroxyisobutyric acid (3-HIB); Branched-chain amino acids (BCAAs); Insulin resistance; Insulin secretion; T2D.

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