Obesity/insulin resistance rather than liver fat increases coagulation factor activities and expression in humans

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Increased liver fat may be caused by insulin resistance and adipose tissue inflammation or by the common I148M variant in PNPLA3 at rs738409, which lacks both of these features. We hypothesised that obesity/insulin resistance rather than liver fat increases circulating coagulation factor activities. We measured plasma prothrombin time (PT, Owren method), activated partial thromboplastin time (APTT), activities of several coagulation factors, VWF:RCo and fibrinogen, and D-dimer concentration in 92 subjects divided into groups based on insulin sensitivity [insulin-resistant (‘IR’) versus insulin-sensitive (‘IS’)] and PNPLA3 genotype (PNPLA3148MM/ MI vs PNPLA3148II). Liver fat content (1H-MRS) was similarly increased in ‘IR’ (13 ± 1%) and PNPLA3148MM/MI (12 ± 2%) as compared to ‘IS’ (6 ± 1%, p<0.05) and PNPLA3148II (8 ± 1%, p<0.05), respectively. FVIII, FIX, FXIII, fibrinogen and VWF:RCo activities were increased, and PT and APTT shortened in ‘IR’ versus ‘IS’, in contrast to these factors being similar between PNPLA3148MM/MI and PNPLA3148II groups. In subjects undergoing a liver biopsy and entirely lacking the I148M variant, insulin-resistant subjects had higher hepatic expression of F8, F9 and FGG than equally obese insulin-sensitive subjects. Expression of pro-inflammatory genes in adipose tissue correlated positively with PT (% of normal), circulating FVIII, FIX, FXI, VWR:RCo and fibrinogen, and expression of anti-inflammatory genes negatively with PT (%), FIX and fibrinogen. We conclude that obesity/insulin resistance rather than an increase in liver fat is associated with a procoagulant plasma profile. This reflects adipose tissue inflammation and increased hepatic production of coagulation factors and their susceptibility for activation.

Detaljer

Författare
  • Susanna Lallukka
  • Panu K. Luukkonen
  • You Zhou
  • Elina Isokuortti
  • Marja Leivonen
  • Anne Juuti
  • Antti Hakkarainen
  • Marju Orho-Melander
  • Nina Lundbom
  • Vesa M. Olkkonen
  • Riitta Lassila
  • Hannele Yki-Järvinen
Enheter & grupper
Externa organisationer
  • Helsinki University Central Hospital
  • Minerva Foundation Institute for Medical Research
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes

Nyckelord

Originalspråkengelska
Sidor (från-till)286-294
Antal sidor9
TidskriftThrombosis and Haemostasis
Volym117
Utgivningsnummer2
StatusPublished - 2017
PublikationskategoriForskning
Peer review utfördJa