H Yki-Järvinen

Minerva Foundation Institute for Medical Research, Helsinki, Southern Finland Province, Finland

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Publications (343)2223.66 Total impact

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    ABSTRACT: Objectives: Patients with type 1 diabetes (T1DM) lack the portal/peripheral insulin gradient, which might diminish insulin stimulation of hepatic lipogenesis and protect against development of non-alcoholic fatty liver disease (NAFLD). We compared liver fat content and insulin sensitivity of hepatic glucose production and lipolysis between overweight T1DM patients and non-diabetic subjects. Materials and Methods: We compared 32 overweight adult T1DM patients and 32 non-diabetic subjects matched for age, BMI and gender. Liver fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS), body composition by MRI and insulin sensitivity using the euglycemic hyperinsulinemic clamp technique (insulin 0.4mU/kg·min combined with infusion of D-[3-(3)H]glucose). We also hypothesized that low liver fat might protect from obesity-associated increases in insulin requirements and, therefore, determined insulin requirements across BMI categories in 3164T1DM patients. Results: Liver fat content was significantly lower in T1DM patients than in non-diabetic subjects [0.6(25th-75th quartiles, 0.3-1.1)% vs. 9.0(3.0-18.0)%; p<0.001]. The endogenous rate of glucose production (Ra) during euglycemic hyperinsulinemia was significantly lower [0.4(-0.7-0.8) mg/kg ffm·min vs. 0.9(0.2-1.6) mg/kg ffm·min; p=0.012] and the % suppression of endogenous Ra by insulin was significantly greater [89(78-112)% vs. 77(50-94)%; p=0.009] in T1DM patients than in non-diabetic subjects. Serum NEFA concentrations during euglycemic hyperinsulinemia were significantly lower [78.5(33.0-155.0)μmol/L vs. 306(200.0-438.0)μmol/L; p<0.001] and the % suppression of NEFA significantly higher [89.1(78.6-93.3)% vs. 51.4(36.5-71.1)%; p<0.001] in T1DM patients than in non-diabetic subjects. Insulin doses were similar across BMI categories. Conclusions: T1DM patients might be protected from steatosis and hepatic insulin resistance. Obesity may not increase insulin requirements in T1DM.
    Journal of Clinical Endocrinology &amp Metabolism 11/2014; · 6.31 Impact Factor
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    ABSTRACT: Aims The Glu167Lys (E167K) variant in TM6SF2 was recently shown to influence liver fat (LFAT) content. We aimed at studying how the variant influences the circulating triacylglycerol (TAG) signature and whether it influences hepatic or adipose tissue insulin sensitivity. Methods We genotyped 300 Finnish subjects for E167K (rs58542926) in TM6SF2 and for I148M (rs738409) in PNPLA3 in whom LFAT was measured using 1H-MRS and circulating lipids by UPLC-MS. We compared plasma lipidome between E167K carriers (TM6SF2EK/KK) and non-carriers (TM6SF2EE), and between three groups of NAFLD: i) carriers of E167K but not the I148M variant in PNPLA3 (‘TM6SF2 NAFLD’), ii) carriers of the I148M but not 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 LFAT content was 34% higher in TM6SF2EK/KK (13.07±1.57%) than TM6SF2EE (9.77±0.58%, p = 0.013). Insulin sensitivities of glucose production and lipolysis were significantly higher at any given LFAT in the TM6SF2EK/KK than in the TM6SF2EE group. Comparison of 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 distinct subtype of NAFLD characterized by preserved insulin sensitivity of lipolysis and hepatic glucose production and lack of hypertriglyceridemia despite clearly increased LFAT content.
    Journal of Hepatology 10/2014; · 10.40 Impact Factor
  • Canadian Journal of Diabetes 10/2014; 38(5). · 0.46 Impact Factor
  • Canadian Journal of Diabetes 10/2014; 38(5). · 0.46 Impact Factor
  • Canadian Journal of Diabetes 10/2014; 38(5). · 0.46 Impact Factor
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    ABSTRACT: To compare efficacy and safety of new insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in people with type 2 diabetes using basal insulin (≥42 U/day) plus oral antihyperglycemic drugs (OADs).
    Diabetes Care 09/2014; · 8.57 Impact Factor
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    ABSTRACT: miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. The endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance. Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and "whitening" of interscapular brown fat. Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte-like phenotype and reduced expression of several miRNAs. Brown preadipocyte whitening was partially reversed by expression of miR-365, a miRNA known to promote brown fat differentiation; however, introduction of other miRNAs, including miR-346 and miR-362, also contributed to reversal of the loss of the dicer phenotype. Interestingly, fat samples from patients with HIV-related lipodystrophy exhibited a substantial downregulation of dicer mRNA expression. Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy.
    The Journal of clinical investigation. 07/2014;
  • Diabetologia 05/2014; · 6.88 Impact Factor
  • Hannele Yki-Järvinen
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    ABSTRACT: Metabolic syndrome is a cluster of metabolic abnormalities that identifies people at risk of diabetes and cardiovascular disease, whereas non-alcoholic fatty liver disease (NAFLD) is defined as a disorder with excess fat in the liver due to non-alcoholic causes. Two key components of metabolic syndrome, glucose and triglycerides, are overproduced by the fatty liver. The liver is therefore a key determinant of metabolic abnormalities. The prevalence of both metabolic syndrome and NAFLD increases with obesity. Other acquired causes for both disorders include excessive intake of simple sugars and physical inactivity. Both disorders predict type 2 diabetes, cardiovascular disease, non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma. Because metabolic syndrome can be defined in many different ways, NAFLD might be a more direct predictor of these diseases. Half of people with NAFLD carry at least one variant (G) allele at rs738409 in the PNPLA3 gene, which is associated with high liver fat content. Steatosis in PNPLA3-associated NAFLD is not accompanied by features of metabolic syndrome. All forms of NAFLD increase the risk of NASH, cirrhosis, and hepatocellular carcinoma.
    The lancet. Diabetes & endocrinology. 04/2014;
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    ABSTRACT: Knowledge of liver volume is needed in the preoperative screening of liver transplant donors and in pharmacokinetic studies. In previous studies, body weight, surface area, age and gender have been identified as predictors of total liver volume, but the impact of non-alcoholic fatty liver disease (NAFLD) independent of body size on liver volume has not been determined. We examined whether and to what extent liver fat due to NAFLD influences liver volume. We quantified the % liver fat by proton magnetic resonance spectroscopy ((1) H-MRS) and liver total, lean and fat volumes using magnetic resonance imaging (MRI) in 112 subjects (62 women, 50 men), who were characterized with respect to metabolic parameters associated with NAFLD. 45% of the subjects had NAFLD (% liver fat 12.5±4.5% vs. 1.8±1.6%, NAFLD vs. no NAFLD, p<0.001). Total liver volume was 29% higher in subjects with NAFLD (1.91±0.45 L) than in those with no NAFLD (1.49±0.31 L, p<0.001). In multiple linear regression analysis, the % liver fat and body weight independently explained variation in total liver volume (r(2) =0.42, p<0.001). The r-values for the relationship between metabolic parameters and the total liver fat volume were not significantly better than those between metabolic parameters and the % liver fat. Both body weight and NAFLD increase liver volume independent of each other. Measurement of liver fat by (1) H-MRS allows accurate quantification of NAFLD and calculation of total liver volume.
    Hepatology Research 04/2014; · 2.22 Impact Factor
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    ABSTRACT: The I148M substitution in PNPLA3 (PNPLA3(I148M)) determines a genetic form of non-alcoholic fatty liver disease. To elucidate the mode of PNPLA3 action in human hepatocytes, we studied effects of wild-type PNPLA3 (PNPLA3(WT)) and PNPLA3(I148M) on HuH7 cell lipidome after [(13)C]glycerol labelling, cellular turnover of [D17]oleic acid in triacylglycerols (TAGs), and subcellular distribution of the protein variants. PNPLA3(I148M) induced a net accumulation of unlabelled TAGs, but not newly synthesized total [(13)C]TAGs. Principal component analysis (PCA) revealed that both PNPLA3(WT) and PNPLA3(I148M) induced a relative enrichment of TAGs with saturated or monounsaturated fatty acids, with concurrent enrichment of polyunsaturated phosphatidylcholines. PNPLA3(WT) associated in PCA with newly synthesized [(13)C]TAGs, particularly 52:1 and 50:1, while PNPLA3(I148M) associated with similar pre-existing TAGs. PNPLA3(WT) overexpression resulted in increased [D17]oleic acid labelling of TAGs during 24 h, and after longer incubations their turnover was accelerated, effects not detected with PNPLA3(I148M). PNPLA3(I148M) localized more extensively to lipid droplets (LD) than PNPLA3(WT), suggesting that the substitution alters distribution of PNPLA3 between LD and endoplasmic reticulum/cytosol. This study reveals a function of PNPLA3 in fatty acid-selective TAG remodelling, resulting in increased TAG saturation. A defect in TAG remodelling activity likely contributes to the TAG accumulation observed in cells expressing PNPLA3(I148M).
    The Journal of Lipid Research 02/2014; · 4.73 Impact Factor
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    ABSTRACT: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology. Clinical characteristics, PNPLA3 genotype at rs738409, and serum cytokeratin 18 fragments were measured in 296 consecutive bariatric surgery patients who underwent a liver biopsy to discover and validate a NASH score ('NASH score'). We also defined the cut-off for NASH for a previously validated NAFLD liver fat score to diagnose NASH in the same cohort ('NASH liver fat score'). Both scores were validated in an Italian cohort comprising of 380, mainly non-bariatric surgery patients, who had undergone a liver biopsy for NASH. The cut-offs were utilized in the Finnish population-based D2D-study involving 2849 subjects (age 45-74 years) to estimate the population prevalence of NASH. The final 'NASH Score' model included PNPLA3 genotype, AST and fasting insulin. It predicted NASH with an AUROC 0.774 (0.709, 0.839) in Finns and 0.759 (0.711, 0.807) in Italians (NS). The AUROCs for 'NASH liver fat score' were 0.734 (0.664, 0.805) and 0.737 (0.687, 0.787), respectively. Using 'NASH liver fat score' and 'NASH Score', the prevalences of NASH in the D2D study were 4.2% (95% CI: 3.4, 5.0) and 6.0% (5.0, 6.9%). Sensitivity analysis was performed by taking into account stochastic false-positivity and false-negativity rates in a Bayesian model. This analysis yielded population prevalences of NASH of 3.1% (95% stimulation limits 0.2-6.8%) using 'NASH liver fat score' and 3.6% (0.2-7.7%) using 'NASH Score'. Population prevalence of NASH in 45-74 year old Finnish subjects is ∼5%.
    Journal of Hepatology 12/2013; · 9.86 Impact Factor
  • Hua Bian, Antti Hakkarainen, Nina Lundbom, Hannele Yki-Järvinen
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    ABSTRACT: Objective: To compare effects of similar weight loss induced either by a short-term low carbohydrate or a long-term hypocaloric diet, and to determine effects of high carbohydrate overfeeding on liver total, lean and fat volumes. Design and Methods: Liver total, lean and fat volumes were measured before and after i) a 6-day low carbohydrate diet (n=17), ii) a 7-month standard hypocaloric diet (n=26) and iii) a 3-week high carbohydrate diet (n=17), by combining magnetic resonance imaging and proton magnetic resonance spectroscopy techniques. Results: At baseline, three groups were comparable with respect to age, BMI, liver volumes and the % liver fat. Body weight decreased similarly by the short-term and long-term hypocaloric diets. Liver total volume decreased significantly more during the short-term low carbohydrate (-22±2%) than the long-term (-7±2%) hypocaloric diet (p<0.001). This was due to a greater decrease in liver lean volume in the short-term (-20±2%) than the long-term (-4±2%) weight loss group (p<0.001). Decreases in liver fat were comparable. Liver volume increased by 9±3% by overfeeding (p<0.02 for before vs. after). Conclusions: These data support use of a short-term low carbohydrate diet whenever a reduction in liver volume is desirable. Overeating carbohydrate is harmful because it increases liver volume.
    Obesity 09/2013; · 4.39 Impact Factor
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    ABSTRACT: Context:Obesity is associated with increased circulating 17β-estradiol (E2) but less is known about E2 concentrations in adipose tissue. In addition to E2, adipose tissue synthesizes E2 fatty acyl esters (E2-FAE).Objective:The aim was to compare estrogen concentrations and expression of estrogen-converting enzymes in adipose tissue between severely obese men and women.Design and Setting:Tissue samples were obtained during elective surgery in University Central Hospital in the years 2008-2011.Patients:We studied 14 men and 22 premenopausal women undergoing bariatric surgery and 10 control women operated for non-malignant reasons.Interventions:Paired samples were taken from abdominal subcutaneous and visceral adipose tissue and serum and analyzed for E2 and E2-FAE by fluoroimmunoassay and liquid chromatography-tandem mass spectrometry. mRNA expression of genes was analyzed by qPCR.Results:Compared to men, E2 levels in subcutaneous adipose tissue in obese women were higher, along with higher relative mRNA expressions of steroid sulfatase and 17β-hydroxysteroid dehydrogenases 1, 7, and 12. In men, E2-FAE concentrations in adipose tissue were similar to E2 but in women significantly lower compared to E2. Adipose tissue E2-FAE and serum E2-FAE levels correlated positively in obese subjects. Serum E2 did not significantly correlate with E2 concentration or mRNA expression of genes in adipose tissue in obese men or women.Conclusions:The production of E2 by the large adipose mass was not reflected by increased circulating E2 concentrations in severely obese men or women. However, adipose tissue may contribute to concentrations of serum E2-FAE.
    The Journal of Clinical Endocrinology and Metabolism 09/2013; · 6.31 Impact Factor
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    ABSTRACT: OBJECTIVE To evaluate the efficacy and long-term safety of linagliptin added to basal insulins in type 2 diabetes inadequately controlled on basal insulin with or without oral agents.RESEARCH DESIGN AND METHODSA total of 1,261 patients (HbA1c ≥7.0% [53 mmol/mol] to ≤10.0% [86 mmol/mol]) on basal insulin alone or combined with metformin and/or pioglitazone, were randomized (1:1) to double-blind treatment with linagliptin 5 mg once daily or placebo for ≥52 weeks. The basal insulin dose was kept unchanged for 24 weeks but could thereafter be titrated according to fasting plasma glucose levels at the investigators' discretion. The primary end point was the mean change in HbA1c from baseline to week 24. The safety analysis incorporated data up to a maximum of 110 weeks.RESULTSAt week 24, HbA1c changed from a baseline of 8.3% (67 mmol/mol) by -0.6% (-6.6 mmol/mol) and by 0.1% (1.1 mmol/mol) with linagliptin and placebo, respectively (treatment difference -0.65% [95% CI -0.74 to -0.55] (-7.1 mmol/mol); P < 0.0001). Despite the option to uptitrate basal insulin, it was adjusted only slightly upward (week 52, linagliptin 2.6 IU/day, placebo 4.2 IU/day; P < 0.003), resulting in no further HbA1c improvements. Frequencies of hypoglycemia (week 24, linagliptin 22.0%, placebo 23.2%; treatment end, linagliptin 31.4%, placebo 32.9%) and adverse events (linagliptin 78.4%, placebo 81.4%) were similar between groups. Mean body weight remained unchanged (week 52, linagliptin -0.30 kg, placebo -0.04 kg).CONCLUSIONS Linagliptin added to basal insulin therapy significantly improved glycemic control relative to placebo without increasing hypoglycemia or body weight.
    Diabetes care 09/2013; · 7.74 Impact Factor
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    ABSTRACT: We examined whether relative concentrations of circulating triacylglycerols between carriers as compared to non-carriers of PNPLA3(I148M) gene variant display deficiency of triacylglycerols, which accumulate in the liver because of defective lipase activity. We also analyzed effects of obesity associated non-alcoholic fatty liver disease (NAFLD) independent of genotype, and of NAFLD due to either PNPLA3(I148) gene variant or obesity on circulating triacylglycerols. 372 subjects were divided into groups based on PNPLA3 genotype or obesity. Absolute and relative deficiency of distinct circulating triacylglycerols was observed in the PNPLA3(148MM/148MI) as compared to the PNPLA3(148II) group. Obese and 'non-obese' groups had similar PNPLA3 genotypes but the obese were insulin-resistant. Liver fat was similarly increased in obese and PNPLA3(148MM/148MI) groups. Relative concentrations of triacylglycerols in the obese vs. 'non-obese' displayed multiple changes. These closely resembled those between obese subjects with NAFLD but without PNPLA3(I148M) vs. those with the I148M variant andNAFLDConclusions Etiology of NAFLD influences circulating triacylglycerol profiles. 'PNPLA3 NAFLD' is associated with relative deficiency of triacylglycerols, supporting the idea that the I148M variant impedes intrahepatocellular lipolysis rather than stimulates triacylglycerol synthesis. Obese NAFLD is associated with multiple changes in triacylglycerols, which can be attributed to obesity/insulin resistance rather than increased liver fat content per se.
    Diabetes 09/2013; · 7.90 Impact Factor
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    ABSTRACT: We examined whether analysis of lipids by ultra-performance liquid chromatography (UPLC) coupled to MS allows the development of a laboratory test for non-alcoholic fatty-liver disease (NAFLD), and how a lipid-profile biomarker compares with the prediction of NAFLD and liver-fat content based on routinely available clinical and laboratory data. We analysed the concentrations of molecular lipids by UPLC-MS in blood samples of 679 well-characterised individuals in whom liver-fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS) or liver biopsy. The participants were divided into biomarker-discovery (n = 287) and validation (n = 392) groups to build and validate the diagnostic models, respectively. Individuals with NAFLD had increased triacylglycerols with low carbon number and double-bond content while lysophosphatidylcholines and ether phospholipids were diminished in those with NAFLD. A serum-lipid signature comprising three molecular lipids ('lipid triplet') was developed to estimate the percentage of liver fat. It had a sensitivity of 69.1% and specificity of 73.8% when applied for diagnosis of NAFLD in the validation series. The usefulness of the lipid triplet was demonstrated in a weight-loss intervention study. The liver-fat-biomarker signature based on molecular lipids may provide a non-invasive tool to diagnose NAFLD, in addition to highlighting lipid molecular pathways involved in the disease.
    Diabetologia 07/2013; · 6.88 Impact Factor
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    ABSTRACT: Objective: Adipocyte hypertrophy has been suggested to be causally linked with inflammation and systemic insulin resistance. The aim of the study was to determine whether increased adipocyte size is associated with increased liver fat content due to nonalcoholic fatty liver disease (NAFLD) in humans independent of obesity, fat distribution and genetic variation in the patatin-like phospholipase domain-containing 3 gene (PNPLA3; adiponutrin) at rs738409. Design and Methods: One hundred nineteen non-diabetic subjects in a cross-sectional study with a median age of 39 years, mean ± SD BMI of 30.0 ± 5.7 kg m(-2) were studied. Abdominal subcutaneous (SC) adipocyte size, liver fat [proton magnetic resonance spectroscopy ((1) H-MRS)], intra-abdominal (IA), and abdominal SC adipose tissue volumes [magnetic resonance imaging (MRI)] and the PNPLA3 genotype at rs738409 were determined. Univariate and multiple linear regression analysis were used to identify independent predictors of liver fat content. Results: In multiple linear regression analysis, age, gender, BMI, the IA/SC ratio, and PNPLA3 genotype explained 42% of variation in liver fat content. Addition of adipocyte size (P < 0.0001) to the model increased the percent of explanation to 53%. Thus, 21% of known variation in liver fat could be explained by adipocyte size alone. Conclusions: Increased adipocyte size highly significantly contributes to liver fat accumulation independent of other causes.
    Obesity 06/2013; 21(6):1174-9. · 4.39 Impact Factor
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    ABSTRACT: We investigated: 1) the ability of purified glargine (GLA), metabolites 1 (M1) and 2 (M2), IGF-I, and NPH insulin to activate the insulin receptor (IR)-A and IR-B and IGF-I receptor (IGF-IR) in vitro; 2) plasma concentrations of GLA, M1, and M2 during long-term insulin therapy in type 2 diabetic patients; and 3) IR-A and IR-B activation in vitro induced by serum from patients treated with GLA or NPH insulin. A total of 104 patients (age 56.3 ± 0.8 years, BMI 31.4 ± 0.5 kg/m(2), and A1C 9.1 ± 0.1% [mean ± SE]) were randomized to GLA or NPH insulin therapy for 36 weeks. Plasma concentrations of GLA, M1, and M2 were determined by liquid chromatography-tandem mass spectrometry assay. IR-A, IR-B, and IGF-IR autophosphorylation was induced by purified hormones or serum by kinase receptor activation assays. In vitro, M1 induced comparable IR-A, IR-B, and IGF-IR autophosphorylation (activation) as NPH insulin. After 36 weeks, M1 increased from undetectable (<0.2 ng/mL) to 1.5 ng/mL (0.9-2.1), while GLA and M2 remained undetectable. GLA dose correlated with M1 (r = 0.84; P < 0.001). Serum from patients treated with GLA or NPH insulin induced similar IR-A and IR-B activation. These data suggest that M1 rather than GLA mediates GLA effects and that compared with NPH insulin, GLA does not increase IGF-IR signaling during long-term insulin therapy in type 2 diabetes.
    Diabetes 04/2013; · 7.90 Impact Factor
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    ABSTRACT: AIMS/HYPOTHESIS: The rs738409 C>G single-nucleotide polymorphism in PNPLA3 leads to a missense mutation (I148M) which increases liver fat but does not cause insulin resistance. We hypothesised that patients with non-alcoholic fatty liver disease (NAFLD) due to the PNPLA3 variant ('PNPLA3 NAFLD' = PNPLA3-148MM) do not have adipose tissue (AT) inflammation in contrast with those with NAFLD due to obesity ('obese NAFLD'). METHODS: Biopsy specimens of AT were taken, and PNPLA3 genotype and liver fat ((1)H-magnetic resonance spectroscopy) were determined in 82 volunteers, who were divided into groups based on either median BMI (obese 36.2 ± 0.7 kg/m(2); non-obese 26.0 ± 0.4 kg/m(2)) or PNPLA3 genotype. All groups were similar with respect to age and sex. The PNPLA3 subgroups were equally obese (PNPLA3-148MM, 31.1 ± 1.3 kg/m(2); PNPLA3-148II, 31.2 ± 0.8 kg/m(2)), while the obese and non-obese subgroups had similar PNPLA3 genotype distribution. Gene expression of proinflammatory (MCP-1, CD68) and anti-inflammatory (Twist1, ADIPOQ) markers was measured using quantitative real-time RT-PCR. RESULTS: Liver fat was similarly increased in obese NAFLD (9.5 ± 1.3% vs 5.1 ± 0.9%, obese vs non-obese, p = 0.007) and PNPLA3 NAFLD (11.4 ± 1.7% vs 5.3 ± 0.8%, PNPLA3-148MM vs PNPLA3-148II, p < 0.001). Fasting serum insulin was higher in the obese than the non-obese group (76 ± 6 vs 47 ± 6 pmol/l, p < 0.001), but similar in PNPLA3-148MM and PNPLA3-148II (60 ± 8 vs 62 ± 5 pmol/l, NS). In obese vs non-obese, MCP-1 and CD68 mRNAs were upregulated, whereas those of Twist1 and ADIPOQ were significantly downregulated. AT gene expression of MCP-1, CD68, Twist1 and ADIPOQ was similar in PNPLA3-148MM and PNPLA3-148II groups. CONCLUSIONS/INTERPRETATION: PNPLA3 NAFLD is characterised by an increase in liver fat but no insulin resistance or AT inflammation, while obese NAFLD has all three of these features.
    Diabetologia 01/2013; · 6.88 Impact Factor

Publication Stats

18k Citations
2,223.66 Total Impact Points


  • 2008–2014
    • Minerva Foundation Institute for Medical Research
      Helsinki, Southern Finland Province, Finland
  • 1984–2014
    • University of Helsinki
      • • Department of Oral Medicine
      • • Institute for Molecular Medicine Finland (FIMM)
      • • Department of Internal Medicine
      Helsinki, Southern Finland Province, Finland
  • 2013
    • Fudan University
      Shanghai, Shanghai Shi, China
  • 2007–2013
    • VTT Technical Research Centre of Finland
      Esbo, Southern Finland Province, Finland
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 2012
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
  • 2004–2012
    • Karolinska Institutet
      • • Centrum för molekylär medicin - CMM
      • • Institutionen för medicin, Huddinge
      Solna, Stockholm, Sweden
  • 1984–2012
    • Helsinki University Central Hospital
      • • Department of Medicine
      • • Department of Clinical Physiology and Nuclear Medicine
      • • Department of Psychiatry
      • • Department of Obstetrics and Gynaecology
      Helsinki, Southern Finland Province, Finland
  • 2006
    • University of Oxford
      • Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM)
      Oxford, ENG, United Kingdom
  • 2003
    • ORTON Foundation, Helsinki, Finland
      Helsinki, Southern Finland Province, Finland
  • 1995–2003
    • University of Turku
      • • Turku PET Centre
      • • Department of Clinical Neurophysiology
      Turku, Western Finland, Finland
    • Turku PET Centre
      Turku, Province of Western Finland, Finland
  • 1999
    • Joslin Diabetes Center
      Boston, Massachusetts, United States
    • The University of Edinburgh
      • Medical Genetics Unit
      Edinburgh, SCT, United Kingdom
  • 1997–1998
    • University of Texas Health Science Center at San Antonio
      • Division of Hospital Medicine
      San Antonio, Texas, United States
    • University of Padova
      Padua, Veneto, Italy
    • Università di Pisa
      Pisa, Tuscany, Italy
  • 1996–1998
    • Texas Tech University Health Sciences Center
      • Department of Medicine
      Lubbock, TX, United States
  • 1991
    • University of Washington Seattle
      • Division of General Internal Medicine
      Seattle, WA, United States
  • 1987–1989
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      Maryland, United States