oru.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Circulating triacylglycerol signatures and insulin sensitivity in NAFLD associated with the E167K variant in TM6SF2
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Minerva Foundation Institute for Medical Research, Helsinki, Finland; CIBERDEM, Endocrinology Unit, Joan XXIII University Hospital, IISPV Pere Virgili Health Research Institute, Rovira i Virgili University, Tarragona, Spain.
Steno Diabetes Center, Gentofte, Denmark.ORCID iD: 0000-0002-2856-9165
Örebro University, School of Science and Technology. Steno Diabetes Center, Gentofte, Denmark.
Show others and affiliations
2015 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 62, no 3, p. 657-663, article id S0168-8278(14)00739-9Article in journal (Refereed) Published
Abstract [en]

BACKGROUND & AIMS: The Glu167Lys (E167K) variant in the transmembrane 6 superfamily member 2 protein (TM6SF2) was recently shown to influence liver fat (LFAT) content. We aimed at studying how this variant influences circulating triacylglycerol (TAG) signatures and whether it influences hepatic or adipose tissue insulin sensitivity.

METHODS: We genotyped 300 Finnish subjects for the E167K (rs58542926) variant in TM6SF2 and for the I148M (rs738409) variant in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) in whom LFAT was measured using 1H-MRS and circulating lipids by UPLC-MS. We compared the plasma lipidome between E167K carriers (TM6SF2EK/KK) and non-carriers (TM6SF2EE), and between three groups of NAFLD: (i) carriers of the E167K but not of the I148M variant in PNPLA3 ('TM6SF2 NAFLD'), (ii) carriers of the I148M but not of the E167K variant ('PNPLA3 NAFLD'), and (iii) non-carriers of either risk allele ('Non-risk NAFLD'). Hepatic and adipose tissue insulin sensitivities were measured using the euglycemic hyperinsulinemic clamp technique combined with infusion of [3-3H]glucose in 111 subjects.

RESULTS: The LFAT content was 34% higher in the TM6SF2EK/KK (13.07±1.57%) than in the TM6SF2EE group (9.77±0.58%, p=0.013). The effect of insulin on glucose production and lipolysis were significantly higher in the TM6SF2EK/KK than in the TM6SF2EE group. Comparison of the three NAFLD groups with similar LFATs showed that both the 'TM6SF2 NAFLD' and 'PNPLA3 NAFLD' had significantly lower triglyceride levels and were characterized by lower levels of most common TAGs compared to the 'Non-risk NAFLD' group.

CONCLUSIONS: We conclude that the E167K variant in TM6SF2 is associated with a distinct subtype of NAFLD, characterized by preserved insulin sensitivity with regard to lipolysis, hepatic glucose production and lack of hypertriglyceridemia despite a clearly increased LFAT content.

Place, publisher, year, edition, pages
Elsevier, 2015. Vol. 62, no 3, p. 657-663, article id S0168-8278(14)00739-9
Keywords [en]
Glucose production, Lipolysis, Liver, Magnetic resonance spectroscopy, Mass spectrometry
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-63702DOI: 10.1016/j.jhep.2014.10.010ISI: 000349855400023PubMedID: 25457209Scopus ID: 2-s2.0-84923064699OAI: oai:DiVA.org:oru-63702DiVA, id: diva2:1169267
Funder
Swedish Heart Lung FoundationSwedish Research Council
Note

Funding agencies:

Academy of Finland

European Union/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative 115372

Sigrid Juselius Foundation

EVO Foundation

Novo Nordisk Foundation

Pahlsson

Gemma Llaurado

Instituto de Salud Carlos III (Spain) CM12/00044

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-01-30Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records BETA

Oresic, MatejHyötyläinen, Tuulia

Search in DiVA

By author/editor
Oresic, MatejHyötyläinen, Tuulia
By organisation
School of Science and Technology
In the same journal
Journal of Hepatology
Gastroenterology and Hepatology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 35 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf