scholarly journals Hepatic Glucokinase Expression Is Associated with Lipogenesis and Fatty Liver in Humans

2011 ◽  
Vol 96 (7) ◽  
pp. E1126-E1130 ◽  
Author(s):  
Andreas Peter ◽  
Norbert Stefan ◽  
Alexander Cegan ◽  
Mareike Walenta ◽  
Silvia Wagner ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Human Liver ◽  
De Novo ◽  
Fat Content ◽  
De Novo Lipogenesis ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Human Liver Biopsies ◽  
Triglyceride Content ◽  
Liver Biopsies

Abstract Background/Aims: Glucokinase (GCK) phosphorylates glucose to form glucose 6-phosphate and thereby regulates hepatic glucose disposal and activates hepatic lipogenesis. Hepatic GCK activity is regulated on the level of GCK mRNA expression and by the inhibitory glucokinase regulatory protein. In this study, we aimed to investigate the relation between GCK mRNA expression and markers of lipogenesis as well as liver fat content in human liver biopsies. Additionally, we investigated whether genetic variation in the liver specific GCK promoter determines liver fat content in humans. Methods: Hepatic mRNA expression and liver triglyceride content was analyzed in 50 human liver biopsies. In a second cohort of 330 individuals, liver fat was precisely measured by 1H magnetic resonance spectroscopy. Results: Hepatic GCK mRNA expression is associated with triglyceride content in human liver biopsies (r = 0.50, P = 0.0002). Furthermore, hepatic GCK mRNA expression is associated with lipogenic gene expression (fatty acid synthase, r = 0.49, P = 0.0003; acetyl-coenzyme A carboxylase-α, r = 0.44, P = 0.0015, and acetyl-coenzyme A carboxylase-β, r = 0.48, P = 0.0004) and the de novo lipogenesis index (r = 0.36, P = 0.01). In support of these findings, the single-nucleotide polymorphism rs2041547 in the liver-specific GCK promoter is associated with liver fat content in prediabetic individuals (P = 0.047). Conclusions: In this study, we demonstrate for the first time that GCK mRNA expression is associated with markers of de novo lipogenesis and liver triglyceride content in humans. This suggests that increased GCK activity may induce fatty liver and its metabolic and hepatic consequences in humans. Thus, the widely used approach to nonspecifically activate β-cell and hepatic GCK to treat diabetes mellitus is therefore questionable and may cause serious side effects.

scholarly journals Paradoxical Dissociation Between Hepatic Fat Content and De Novo Lipogenesis Due to PNPLA3 Sequence Variant

2015 ◽  
Vol 100 (5) ◽  
pp. E821-E825 ◽  
Author(s):  
Rosellina M. Mancina ◽  
Niina Matikainen ◽  
Cristina Maglio ◽  
Sanni Söderlund ◽  
Nina Lundbom ◽  
...  
Keyword(s):  
De Novo ◽  
Fat Content ◽  
De Novo Lipogenesis ◽  
Liver Fat ◽  
Sequence Variant ◽  
Deuterated Water ◽  
Epidemic Disease ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Hepatic Fat

Abstract Context: Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic disease characterized by increased hepatic fat, due to an imbalance between synthesis and removal of hepatic lipids. In particular, increased hepatic de novo lipogenesis (DNL) is a key feature associated with NAFLD. The genetic variations I148M in PNPLA3 and E167K in TM6SF2 confer susceptibility to NAFLD. Objective: Here we aimed to investigate the contribution of DNL to liver fat accumulation in the PNPLA3 I148M or TM6SF2 E167K genetic determinants of NAFLD. Patients and Methods: The PNPLA3 I148M and TM6SF2 E167K were genotyped in two well-characterized cohorts of Europeans. In the first cohort (Helsinki cohort; n = 88), we directly quantified hepatic DNL using deuterated water. In the second cohort (Milan cohort; n = 63), we quantified the hepatic expression of SREBP1c that we have found previously associated with increased fat content. Liver fat was measured by magnetic resonance proton spectroscopy in the Helsinki cohort, and by histological assessment of liver biopsies in the Milan cohort. Results: PNPLA3 148M was associated with lower DNL and expression of the lipogenic transcription factor SREBP1c despite substantial increased hepatic fat content. Conclusions: Our data show a paradoxical dissociation between hepatic DNL and hepatic fat content due to the PNPLA3 148M allele indicating that increased DNL is not a key feature in all individuals with hepatic steatosis, and reinforces the contribution of decreased mobilization of hepatic triglycerides for hepatic lipid accumulation in subject with the PNPLA3 148M allele.

Gene expression in human NAFLD

2008 ◽  
Vol 294 (5) ◽  
pp. G1281-G1287 ◽  
Author(s):  
Dario Greco ◽  
Anna Kotronen ◽  
Jukka Westerbacka ◽  
Oscar Puig ◽  
Perttu Arkkila ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Human Liver ◽  
Fat Content ◽  
Liver Fat ◽  
Fatty Acid Transport ◽  
Liver Fat Content ◽  
Nonalcoholic Fatty Liver ◽  
Glucose And Lipid Metabolism ◽  
Robust Model

Despite the high prevalence of nonalcoholic fatty liver disease (NAFLD), little is known of its pathogenesis based on study of human liver samples. By the use of Affymetrix GeneChips (17,601 genes), we investigated gene expression in the human liver of subjects with extreme steatosis due to NAFLD without histological signs of inflammation (liver fat 66.0 ± 6.8%) and in subjects with low liver fat content (6.4 ± 2.7%). The data were analyzed by using sequence-based reannotation of Affymetrix probes and a robust model-based normalization method. We identified genes involved in hepatic glucose and lipid metabolism, insulin signaling, inflammation, coagulation, and cell adhesion to be significantly associated with liver fat content. In addition, genes involved in ceramide signaling (MAP2K4) and metabolism (UGCG) were found to be positively associated with liver fat content. Genes involved in lipid metabolism (PLIN, ACADM), fatty acid transport (FABP4, CD36), amino acid catabolism (BCAT1), and inflammation (CCL2) were validated by real-time PCR and were found to be upregulated in subjects with high liver fat content. The data show that multiple changes in gene expression characterize simple steatosis.

Diabetes Remission Clinical Trial (DiRECT)—Plasma Liver Function Tests Reflect Change in Liver Fat Content in Early Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1834-P
Author(s):  
SVIATLANA V. ZHYZHNEUSKAYA ◽  
AHMAD AL-MRABEH ◽  
CARL PETERS ◽  
ALISON C. BARNES ◽  
KIEREN G. HOLLINGSWORTH ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Liver Function ◽  
Liver Function Tests ◽  
Fat Content ◽  
Diabetes Remission ◽  
Liver Fat ◽  
Early Type ◽  
Liver Fat Content

115-LB: Oral Insulin–Induced Reduction in Liver Fat Content in T2DM Patients with Nonalcoholic Steatohepatitis

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 115-LB
Author(s):  
MIRIAM KIDRON ◽  
SHARON PERLES ◽  
REEM KALOTI ◽  
RAMI GHANTOUS ◽  
SUHA F. SANDOUKA ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Fat Content ◽  
Liver Fat ◽  
Oral Insulin ◽  
Liver Fat Content

scholarly journals Liver fat content is independently associated with microalbuminuria in a normotensive, euglycaemic Chinese population: a community-based, cross-sectional study

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e044237
Author(s):  
Xiaoming Li ◽  
Mingfeng Xia ◽  
Hui Ma ◽  
Yu Hu ◽  
Hongmei Yan ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Blood Glucose ◽  
Density Lipoprotein ◽  
Fat Content ◽  
Lipoprotein Cholesterol ◽  
Liver Fat ◽  
Community Based ◽  
Liver Fat Content ◽  
Cross Sectional ◽  
Multivariable Logistic Regression

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is associated with microalbuminuria (MA) in patients with diabetes/pre-diabetes. Whether this association is mediated by blood glucose and blood pressure (BP) remains unclear. This study investigated whether liver fat content (LFC) was associated with MA in a normotensive and non-diabetic population.DesignA cross-sectional substudy.SettingsLFC was determined from the hepatic/renal echogenicity ratio at ultrasound. MA was defined as an albumin-to-creatinine ratio (ACR) of 30–300 µg/mg (early- morning urine sample). Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate LFC as a predictor of MA.ParticipantsBetween May 2010 and June 2011, this cross-sectional, community-based study enrolled residents from Shanghai (China), aged ≥40 years and with normal glucose tolerance and BP.ResultsA total of 550 residents (median age, 57 years; 174 men) were enrolled and stratified according to LFC quartiles. ACR (p<0.001) and MA prevalence (p=0.012) increased across the LFC quartiles. Multivariable logistic regression showed that the OR for MA (per SD increase in LFC) was 1.840 (95% CI 1.173 to 2.887, p=0.008) after adjustment for potential confounders including age, gender, waist-hip ratio, blood urea nitrogen, systolic and diastolic BP, fasting blood glucose, postprandial glucose, low-density lipoprotein-cholesterol, triglycerides, high-density lipoprotein-cholesterol, total cholesterol, estimated glomerular filtration rate and lipid-lowering drugs. The ROC analysis revealed that the optimal LFC cut-off value for predicting MA was 6.82%.ConclusionLFC is independently associated with MA in normotensive, euglycaemic middle-aged and elderly Chinese individuals. Screening for MA in people with NAFLD might facilitate early intervention to minimise kidney disease risk.

scholarly journals A carbohydrate-reduced high-protein diet improves HbA1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trial

Diabetologia ◽  
2019 ◽  
Vol 62 (11) ◽  
pp. 2066-2078 ◽  
Author(s):  
Mads J. Skytte ◽  
Amirsalar Samkani ◽  
Amy D. Petersen ◽  
Mads N. Thomsen ◽  
Arne Astrup ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
High Protein Diet ◽  
Fat Content ◽  
Protein Diet ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Randomised Controlled

Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes

2006 ◽  
Vol 291 (2) ◽  
pp. E282-E290 ◽  
Author(s):  
Riikka Lautamäki ◽  
Ronald Borra ◽  
Patricia Iozzo ◽  
Markku Komu ◽  
Terho Lehtimäki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Liver Steatosis ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Artery Disease ◽  
Myocardial Insulin Resistance ◽  
High Liver

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-d-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 ± 2.0%) and high (17.4 ± 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level ( P = 0.012) and muscle ( P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake ( P = 0.040) and glucose extraction rate ( P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 ( P < 0.05) and lower coronary flow reserve ( P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.

scholarly journals Collagen proline hydroxylase activity and 35S sulphate uptake in human liver biopsies

Gut ◽  
1974 ◽  
Vol 15 (4) ◽  
pp. 260-267 ◽  
Author(s):  
J. OD. McGee ◽  
R. S. Patrick ◽  
M. C. Rodger ◽  
C. M. Luty
Keyword(s):  
Human Liver ◽  
Hydroxylase Activity ◽  
Sulphate Uptake ◽  
Human Liver Biopsies ◽  
Liver Biopsies ◽  
Proline Hydroxylase

scholarly journals The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Trevor J. Orchard ◽  
Bertrand Cariou ◽  
Margery A. Connelly ◽  
James D. Otvos ◽  
Shuyu Zhang ◽  
...  
Keyword(s):  
Insulin Glargine ◽  
Basal Insulin ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Lipoprotein Particles ◽  
Patients With Diabetes

Choline requirement of the preruminant lamb during the first two or three weeks of life

1985 ◽  
Vol 36 (6) ◽  
pp. 829 ◽  
Author(s):  
SJ Al-Ali ◽  
NM Malouf ◽  
DM Walker
Keyword(s):  
Choline Chloride ◽  
Ammonia Excretion ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Butter Oil ◽  
Protein Energy ◽  
Gross Energy ◽  
Ad Libitum ◽  
Milk Replacers

Preruminant male crossbred lambs, aged 1-2 days at the start of the experiment, were bottle-fed on milk replacers containing casein as the sole source of protein for an experimental period of 15-21 days. Choline-deficient diets were used in experiment 1 to determine the effect on the performance of the lambs of thc dictary protein concentration (10, 15 and 25% protein energy), and in experiment 2 of different sources of fat (butter oil, maize oil or lard), unsupplemented, or with supplements of choline chloride or L-cystine. Supplements of choline chloride decreased liver fat content and decreased urinary creatine excretion, irrespective of dietary protein concentration or source of dietary fat. Ira general, urinary ammonia excretion increased as the sulfur amino acid content of the diets increased, but there were interactions with the source of fat, so that although sulfur intake remained constant ammonia excretion was higher with diets containing lard than with those containing maize oil or butter oil. The effect of the supplements of 1,-cystine on liver fat content and urinary creatine excretion was not significantly different from that of the unsupplemented choline-deficient diets. In experiments 3 and 4 a choline-deficient diet with 25% protein energy and butter oil as the source of fat was supplemented with graded amounts of choline chloride. Energy intake was ad libitum, or restricted to 80% of ad libitum. When the lambs were fed ad libitum there was a significant decrease in liver fat content even with the smallest supplement of choline chloride (c. 9 mg MJ-1 gross energy), but no significant effect when energy intake was restricted. Since liveweight gains and nitrogen balances were unaffected by the presence or absence of the choline supplements it was concluded that in milk replacers containing 25% protein energy from casein, with butter oil as the source of fat, supplementation with choline chloride to provide 9 mg MJ-1 gross energy (233 mg kg-1 dry matter) would be sufficient to prevent the increased deposition of fat in the liver during the 6rst three weeks of life.

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