scholarly journals GLP-1 Responses Are Heritable and Blunted in Acquired Obesity With High Liver Fat and Insulin Resistance

Diabetes Care ◽  
2013 ◽  
Vol 37 (1) ◽  
pp. 242-251 ◽  
Author(s):  
Niina Matikainen ◽  
Leonie H. Bogl ◽  
Antti Hakkarainen ◽  
Jesper Lundbom ◽  
Nina Lundbom ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Fat ◽  
High Liver

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 Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat

Diabetologia ◽  
2005 ◽  
Vol 48 (11) ◽  
pp. 2282-2291 ◽  
Author(s):  
N. Stefan ◽  
F. Machicao ◽  
H. Staiger ◽  
J. Machann ◽  
F. Schick ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adiponectin Receptor ◽  
Liver Fat ◽  
Gene Encoding ◽  
Adiponectin Receptor 1 ◽  
High Liver

scholarly journals Dissociation of Fatty Liver and Insulin Resistance in I148M PNPLA3 Carriers: Differences in Diacylglycerol (DAG) FA18:1 Lipid Species as a Possible Explanation

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1314 ◽  
Author(s):  
Andras Franko ◽  
Dietrich Merkel ◽  
Marketa Kovarova ◽  
Miriam Hoene ◽  
Benjamin Jaghutriz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Normal Liver ◽  
Liver Fat ◽  
Wild Type ◽  
Group 4 ◽  
Allele Group ◽  
Group 2 ◽  
High Liver

Fatty liver is tightly associated with insulin resistance and the development of type 2 diabetes. I148M variant in patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene is associated with high liver fat but normal insulin sensitivity. The underlying mechanism of the disassociation between high liver fat but normal insulin sensitivity remains obscure. We investigated the effect of I148M variant on hepatic lipidome of subjects with or without fatty liver, using the Lipidyzer method. Liver samples of four groups of subjects consisting of normal liver fat with wild-type PNPLA3 allele (group 1); normal liver fat with variant PNPLA3 allele (group 2); high liver fat with wild-type PNPLA3 allele (group 3); high liver fat with variant PNPLA3 allele (group 4); were analyzed. When high liver fat to normal liver fat groups were compared, wild-type carriers (group 3 vs. group 1) showed similar lipid changes compared to I148M PNPLA3 carriers (group 4 vs. group 2). On the other hand, in wild-type carriers, increased liver fat significantly elevated the proportion of specific DAGs (diacylglycerols), mostly DAG (FA18:1) which, however, remained unchanged in I148M PNPLA3 carriers. Since DAG (FA18:1) has been implicated in hepatic insulin resistance, the unaltered proportion of DAG (FA18:1) in I148M PNPLA3 carriers with fatty liver may explain the normal insulin sensitivity in these subjects.

A diet low in sugar reduces the production of atherogenic lipoproteins in men with high liver fat

2015 ◽  
Vol 241 (1) ◽  
pp. e46 ◽  
Author(s):  
M. Umpleby ◽  
F. Shojaee-Moradie ◽  
B. Fielding ◽  
X. Li ◽  
C. Isherwood ◽  
...  
Keyword(s):  
Liver Fat ◽  
High Liver

scholarly journals Fructose and NAFLD: metabolic implications and models of induction in rats

2011 ◽  
Vol 26 (suppl 2) ◽  
pp. 45-50 ◽  
Author(s):  
Gabriela S. F. Castro ◽  
João F. R. Cardoso ◽  
Helio Vannucchi ◽  
Sérgio Zucoloto ◽  
Alceu Afonso Jordão
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Wistar Rats ◽  
Liver Steatosis ◽  
Experimental Designs ◽  
Liver Fat ◽  
Excessive Consumption ◽  
Chronic Models ◽  
Simple Carbohydrates ◽  
Fasted Rats

PURPOSE: The increase in fructose consumption is paralleled by a higher incidence of obesity worldwide. This monosaccharide is linked to metabolic syndrome, being associated with hypertriglyceridemia, hypertension, insulin resistance and diabetes mellitus. It is metabolized principally in the liver, where it can be converted into fatty acids, which are stored in the form of triglycerides leading to NAFLD. Several models of NAFLD use diets high in simple carbohydrates. Thus, this study aimed to describe the major metabolic changes caused by excessive consumption of fructose in humans and animals and to present liver abnormalities resulting from high intakes of fructose in different periods of consumption and experimental designs in Wistar rats. METHODS: Two groups of rats were fasted for 48 hours and reefed for 24 or 48 hours with a diet containing 63% fructose. Another group of rats was fed an diet with 63% fructose for 90 days. RESULTS: Refeeding for 24 hours caused accumulation of large amounts of fat, compromising 100% of the hepatocytes. The amount of liver fat in animals refed for 48 hours decreased, remaining mostly in zone 2 (medium-zonal). In liver plates of Wistar rats fed 63% fructose for 45, 60 and 90 days it's possible to see that there is an increase in hepatocytes with fat accumulation according to the increased time; hepatic steatosis, however, is mild, compromising about 20% of the hepatocytes. CONCLUSIONS: Fructose is highly lipogenic, however the induction of chronic models in NAFLD requires long periods of treatment. The acute supply for 24 or 48 hours, fasted rats can cause big changes, liver steatosis with macrovesicular in all lobular zones.

scholarly journals Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1316 ◽  
Author(s):  
Nicolai Worm
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Body Weight ◽  
Liver Disease ◽  
Glycogen Synthesis ◽  
Liver Fat ◽  
Meal Replacement ◽  
Alcoholic Fatty Liver ◽  
Therapeutic Concept ◽  
The Metabolic Syndrome

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent liver disease in industrialized countries. It is regarded as the hepatic manifestation of the metabolic syndrome (MetS) resulting from insulin resistance. Moreover, insulin resistance impairs glycogen synthesis, postprandially diverting a substantial amount of carbohydrates to the liver and storing them there as fat. NAFLD has far-reaching metabolic consequences involving glucose and lipoprotein metabolism disorders and risk of cardiovascular disease, the leading cause of death worldwide. No pharmaceutical options are currently approved for the treatment of NAFLD. Exercise training and dietary interventions remain the cornerstone of NAFLD treatment. Current international guidelines state that the primary goal of nutritional therapy is to reduce energy intake to achieve a 7%–10% reduction in body weight. Meal replacement therapy (formula diets) results in more pronounced weight loss compared to conventional calorie-restricted diets. However, studies have shown that body mass index (BMI) or weight reduction is not obligatory for decreasing hepatic fat content or to restore normal liver function. Recent studies have achieved significant reductions in liver fat with eucaloric diets and without weight loss through macronutrient modifications. Based on this evidence, an integrative nutritional therapeutic concept was formulated that combines the most effective nutrition approaches termed “liver-fasting.” It involves the temporary use of a low calorie diet (total meal replacement with a specific high-protein, high-soluble fiber, lower-carbohydrate formula), followed by stepwise food reintroduction that implements a Mediterranean style low-carb diet as basic nutrition.

Effect of liver fat on insulin clearance

2007 ◽  
Vol 293 (6) ◽  
pp. E1709-E1715 ◽  
Author(s):  
Anna Kotronen ◽  
Satu Vehkavaara ◽  
Anneli Seppälä-Lindroos ◽  
Robert Bergholm ◽  
Hannele Yki-Järvinen
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fat Content ◽  
Insulin Clearance ◽  
Liver Fat ◽  
Hepatic Insulin Resistance ◽  
Model Assessment ◽  
Liver Fat Content ◽  
Hepatic Insulin Sensitivity ◽  
Impaired Insulin

A fatty liver is associated with fasting hyperinsulinemia, which could reflect either impaired insulin clearance or hepatic insulin action. We determined the effect of liver fat on insulin clearance and hepatic insulin sensitivity in 80 nondiabetic subjects [age 43 ± 1 yr, body mass index (BMI) 26.3 ± 0.5 kg/m2]. Insulin clearance and hepatic insulin resistance were measured by the euglycemic hyperinsulinemic (insulin infusion rate 0.3 mU·kg−1·min−1for 240 min) clamp technique combined with the infusion of [3-3H]glucose and liver fat by proton magnetic resonance spectroscopy. During hyperinsulinemia, both serum insulin concentrations and increments above basal remained ∼40% higher ( P < 0.0001) in the high (15.0 ± 1.5%) compared with the low (1.8 ± 0.2%) liver fat group, independent of age, sex, and BMI. Insulin clearance (ml·kg fat free mass−1·min−1) was inversely related to liver fat content ( r = −0.52, P < 0.0001), independent of age, sex, and BMI ( r = −0.37, P = 0.001). The variation in insulin clearance due to that in liver fat (range 0–41%) explained on the average 27% of the variation in fasting serum (fS)-insulin concentrations. The contribution of impaired insulin clearance to fS-insulin concentrations increased as a function of liver fat. This implies that indirect indexes of insulin sensitivity, such as homeostatic model assessment, overestimate insulin resistance in subjects with high liver fat content. Liver fat content correlated significantly with fS-insulin concentrations adjusted for insulin clearance ( r = 0.43, P < 0.0001) and with directly measured hepatic insulin sensitivity ( r = −0.40, P = 0.0002). We conclude that increased liver fat is associated with both impaired insulin clearance and hepatic insulin resistance. Hepatic insulin sensitivity associates with liver fat content, independent of insulin clearance.

scholarly journals Protein Tyrosine Phosphatase Activity in Insulin-Resistant RodentPsammomys Obesus

2002 ◽  
Vol 3 (3) ◽  
pp. 199-204 ◽  
Author(s):  
Joseph Meyerovitch ◽  
Yigal Balta ◽  
Ehud Ziv ◽  
Joseph Sack ◽  
Eleazar Shafrir
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Food Deprivation ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Protein Band ◽  
Liver Fat ◽  
Albino Rats ◽  
Insulin Resistant ◽  
Ptpase Activity

Phosphotyrosine phosphatase (PTPase) activity and its regulation by overnight food deprivation were studied inPsammomys obesus(sand rat), a gerbil model of insulin resistance and nutritionally induced diabetes mellitus. PTPase activity was measured using a phosphopeptide substrate containing a sequence identical to that of the major site of insulin receptor (IR) β-subunit autophosphorylation. The PTPase activity in membrane fractions was 3.5-, 8.3-, and 5.9-fold lower in liver, fat, and skeletal muscle, respectively, compared with corresponding tissues of albino rat.Western blotting of tissue membrane fractions inPsammomysshowed lower PTPase and IR than in albino rats. The density of PTPase transmembrane protein band was 5.5-fold lower in liver and 12-fold lower in adipose tissue. Leukocyte antigen receptor (LAR) and IR were determined by specific immunoblotting and protein bands densitometry and were also found to be 6.3-fold lower in the liver and 22-fold lower in the adipose tissue in the hepatic membrane fractions. Liver cytosolic PTPase activity after an overnight food deprivation in the nondiabeticPsammomysrose 3.7-fold compared with postprandial PTPase activity, but it did not change significantly in diabetic fasted animals. Similar fasting-related changes were detected in the activity of PTPase derived from membrane fraction. In conclusion, the above data demonstrate that despite the insulin resistance,Psammomysis characterized by low level of PTPase activities in membrane and cytosolic fractions in all 3 major insulin responsive tissues, as well as in liver. PTPase activity does not rise in activity as a result of insulin resistance and nutritionally induced diabetes.

Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy

2004 ◽  
Vol 286 (6) ◽  
pp. E941-E949 ◽  
Author(s):  
Jussi Sutinen ◽  
Katja Kannisto ◽  
Elena Korsheninnikova ◽  
Rachel M. Fisher ◽  
Ewa Ehrenborg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Highly Active Antiretroviral Therapy ◽  
Subcutaneous Adipose Tissue ◽  
Binding Protein ◽  
Lipid Binding ◽  
Liver Fat ◽  
Highly Active ◽  
Subcutaneous Adipose

Highly active antiretroviral therapy (HAART) has improved the prognosis of human immunodeficiency virus (HIV)-infected patients but is associated with severe adverse events, such as lipodystrophy and insulin resistance. Rosiglitazone did not increase subcutaneous fat in patients with HAART-associated lipodystrophy (HAL) in a randomized, double-blind, placebo-controlled trial, although it attenuated insulin resistance and decreased liver fat content. The aim of this study was to examine effects of rosiglitazone on gene expression in subcutaneous adipose tissue in 30 patients with HAL. The mRNA concentrations in subcutaneous adipose tissue were measured using real-time PCR. Twenty-four-week treatment with rosiglitazone (8 mg/day) compared with placebo significantly increased the expression of adiponectin, peroxisome proliferator-activated receptor-γ (PPARγ), and PPARγ coactivator 1 and decreased IL-6 expression. Expression of other genes involved in lipogenesis, fatty acid metabolism, or glucose transport, such as acyl-CoA synthase, adipocyte lipid-binding protein, CD45, fatty acid transport protein-1 and -4, GLUT1, GLUT4, keratinocyte lipid-binding protein, lipoprotein lipase, PPARδ, and sterol regulatory element-binding protein-1c, remained unchanged. Rosiglitazone also significantly increased serum adiponectin concentration. The change in serum adiponectin concentration was inversely correlated with the change in fasting serum insulin concentration and liver fat content. In conclusion, rosiglitazone induced significant changes in gene expression in subcutaneous adipose tissue and ameliorated insulin resistance in patients with HAL. Increased expression of adiponectin might have mediated most of the favorable insulin-sensitizing effects of rosiglitazone in these patients.

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