Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies have revealed that high-fat (HF) diets promote hyperglycaemia, whole-body insulin resistance and non-alcoholic fatty liver disease (NAFLD). Recently, hepatic glucagon resistance has been shown to occur in rats fed a HF diet. More precisely, diet-induced obesity (DIO) reduces the number of hepatic plasma membrane glucagon receptors (GR), which results in a diminished response to glucagon during a hyperglucagonaemic clamp. The present study was undertaken to test the hypothesis that a HF-DIO is associated with a desensitization and destruction of the hepatic GR. We also hypothesized that a single bout of endurance exercise would modify the GR cellular distribution under our DIO model. Male rats were either fed a standard (SD) or a HF diet for two weeks. Each group was subdivided into a non-exercised (Rest) and an acute exercised (EX) group. The HF diet resulted in a reduction of total hepatic GR (55%) and hepatic plasma membrane GR protein content (20%). These changes were accompanied by a significant increase in endosomal and lysosomal GR content with the feeding of a HF diet. The reduction of GR plasma membrane as well as the increase in endosomal GR was strongly correlated with an increase of PKC-alpha, suggesting a role of PKC-alpha in GR desensitization. EX increased significantly PKC-alpha protein content in both diets, suggesting a role of PKC-alpha in EX-induced GR desensitization. The present results suggest that liver lipid infiltration plays a role in reducing glucagon action in the liver through a reduction in total cellular and plasma membrane GR content. Furthermore, the GR desensitization observed in our in vivo model of HF diet-induced hepatic steatosis and in EX individuals may be regulated by PKC-alpha.
 ...
PMID:High-fat diet-induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise. 1705 32

Severe fatty liver, a metabolic disease of dairy cows in early lactation, results in decreased health and reproductive performance, but can be alleviated by treatment with i.v. injections of glucagon. Mild fatty liver in cows effects on health and reproductive performance were determined by treatment with 14-day s.c. injections of glucagon at 7.5 or 15 mg/day. Multiparous Holstein cows (n=32) were grouped into Normal and Susceptible based on liver triacylglycerol concentrations (>1% liver tissue biopsy wet weight) at day 8 postpartum (day 0=day of parturition). Susceptible cows (n=24) were assigned randomly to three groups and s.c. injected with 0mg glucagon [60 ml 0.15M NaCl] [n=8] (same for Normal cows), 2.5 mg glucagon, or 5 mg glucagon every 8 h for 14 days, beginning day 8 postpartum. Mild fatty liver resulted in an increased number of days with elevated body temperature during the injection period, an increased incidence of mastitis after glucagon treatment, increased days to first estrus and insemination, increased days before conception occurred, and decreased conception rate. In cows with mild fatty liver, glucagon (15 mg/day) decreased the number of days with elevated body temperature and the incidence of mastitis after hormone treatment. From these results, we suggest that mild fatty liver is detrimental to health and reproduction of dairy cows and, furthermore, that exogenous glucagon decreases some of these detrimental effects.
 ...
PMID:Exogenous glucagon effects on health and reproductive performance of lactating dairy cows with mild fatty liver. 1712 5

The worldwide increase in degenerative diseases is in part due to modifications in the lifestyle including the diet. Epidemiological, clinical, and experimental evidence shows that soy protein may prevent lipotoxicity in non-adipose tissues during obesity. The molecular mechanism by which soy protein prevents lipotoxicity involves a reduction in the insulin/glucagon ratio, resulting in a down-regulation of lipogenic genes mediated by the transcription factor sterol regulatory element-binding protein (SREBP)-1, and up-regulation of SREBP-2 to reduce serum cholesterol. In addition, soy protein maintains the functionality of adipose tissue-liver axis to prevent hepatic steatosis during the development of obesity.
 ...
PMID:The role of dietary protein on lipotoxicity. 1760 16

Liver fatty acid-binding protein (L-FABP) is a highly conserved key factor in lipid metabolism. Amino acid replacements in L-FABP might alter its function and thereby affect glucose metabolism in lipid-exposed subjects, as indicated by studies in L-FABP knockout mice. Amino acid replacements in L-FABP were investigated in a cohort of 1,453 Caucasian subjects. Endogenous glucose production (EGP), gluconeogenesis, and glycogenolysis were measured in healthy carriers of the only common Thr(94)-to-Ala amino acid replacement (Ala/Ala(94)) vs. age-, sex-, and BMI-matched wild-type (Thr/Thr(94)) controls at baseline and after 320-min lipid/heparin-somatostatin-insulin-glucagon clamps (n = 18). Whole body glucose disposal was further investigated (subset; n = 13) using euglycemic-hyperinsulinemic clamps without and with lipid/heparin infusion. In the entire cohort, the only common Ala/Ala(94) mutation was significantly associated with reduced body weight, which is in agreement with a previous report. In lipid-exposed, individually matched subjects there was a genotype vs. lipid-treatment interaction for EGP (P = 0.009) driven mainly by reduced glycogenolysis in Ala/Ala(94) carriers (0.46 +/- 0.05 vs. 0.59 +/- 0.05 mgxkg(-1)xmin(-1), P = 0.013). The lipid-induced elevation of plasma glucose levels was smaller in Ala/Ala(94) carriers compared with wild types (P < 0.0001). Whole body glucose disposal was not different between lipid-exposed L-FABP genotypes. In summary, the Ala/Ala(94)-mutation contributed significantly to reduced glycogenolysis and less severe hyperglycemia in lipid-exposed humans and was further associated with reduced body weight in a large cohort. Data clearly show that investigation of L-FABP phenotypes in the basal overnight-fasted state yielded incomplete information, and a challenge test was essential to detect phenotypical differences in glucose metabolism between L-FABP genotypes.
 ...
PMID:A Thr94Ala mutation in human liver fatty acid-binding protein contributes to reduced hepatic glycogenolysis and blunted elevation of plasma glucose levels in lipid-exposed subjects. 1769 86

Inulin-type fructans have been tested for their capacity to modulate lipid and glucose metabolism in several animal models. Oligofructose (OFS) decreases food intake, fat mass development, and hepatic steatosis in normal and in obese rats; moreover, it exerts an antidiabetic effect in streptozotocin-treated rats and high-fat-fed mice. In most cases, the beneficial effects of OFS are linked to an increase of glucagon-like peptide-1 (GLP-1) level in the portal vein and of GLP-1 and proglucagon mRNA, its precursor, in the proximal colon. In this organ, OFS increases the number of GLP-1-positive L cells by promoting factors (Neurogenin 3 and NeuroD) involved in the differentiation of stem cells into L cells. The chronic administration of GLP-1 receptor antagonist exendin 9-39 totally prevents the beneficial effects of OFS (improved glucose tolerance, fasting blood glucose, glucose-stimulated insulin secretion, insulin-sensitive hepatic glucose production, and reduced body weight gain). Furthermore GLP-1 receptor knockout mice are completely insensitive to the antidiabetic actions of OFS. These findings highlight the potential interest of enhancing endogenous GLP-1 secretion by inulin-type fructans for the prevention/treatment of obesity and type 2 diabetes. Moreover, OFS is also able to modulate other gastrointestinal peptides (such as PYY and ghrelin) that could be involved in the control of food intake. Several studies in humans already support interest in OFS in the control of satiety, triglyceridemia, or steatohepatitis. The link with gut peptides production in humans remains to be proven.
 ...
PMID:Modulation of glucagon-like peptide 1 and energy metabolism by inulin and oligofructose: experimental data. 1795

Glucocorticoids (GCs) increase hepatic phosphatidate phosphatase (PAP1) activity. This is important in enhancing the liver's capacity for storing fatty acids as triacylglycerols (TAGs) that can be used subsequently for beta-oxidation or VLDL secretion. PAP1 catalyzes the conversion of phosphatidate to diacylglycerol, a key substrate for TAG and phospholipid biosynthesis. PAP1 enzymes in liver include lipin-1A and -1B (alternatively spliced isoforms) and two distinct gene products, lipin-2 and lipin-3. We determined the mechanisms by which the composite PAP1 activity is regulated using rat and mouse hepatocytes. Levels of lipin-1A and -1B mRNA were increased by dexamethasone (dex; a synthetic GC), and this resulted in increased lipin-1 synthesis, protein levels, and PAP1 activity. The stimulatory effect of dex on lipin-1 expression was enhanced by glucagon or cAMP and antagonized by insulin. Lipin-2 and lipin-3 mRNA were not increased by dex/cAMP, indicating that increased PAP1 activity is attributable specifically to enhanced lipin-1 expression. This work provides the first evidence for the differential regulation of lipin activities. Selective lipin-1 expression explains the GC and cAMP effects on increased hepatic PAP1 activity, which occurs in hepatic steatosis during starvation, diabetes, stress, and ethanol consumption.
 ...
PMID:Glucocorticoids and cyclic AMP selectively increase hepatic lipin-1 expression, and insulin acts antagonistically. 1824 16

This study examined the effects of multiple subcutaneous glucagon injections with or without co-administration of oral glycerol on energy status-related blood metabolites and hormones of Holstein dairy cows in the first 2 wk postpartum. Twenty multiparous cows were fed a dry cow ration supplemented with 6 kg of cracked corn during the dry period to increase the likelihood of developing postpartal fatty liver syndrome. Cows with a body condition score of >or=3.5 points (1- to 5-point scale) were assigned randomly to 1 of 4 treatment groups: saline, glucagon, glycerol, or glucagon plus glycerol. Following treatment, serial blood samples were collected over an 8-h period to determine the effects of glucagon and glycerol on blood metabolites and hormones. Treatment effects were determined by comparing the concentrations of metabolites and hormones during the first 4-h period and the entire 8-h period after treatment administration (time 0) with the concentration of the same compounds at time 0 on d 1, 7, and 13 postpartum. Administration of glucagon alone increased concentrations of plasma glucagon and insulin on d 1, 7, and 13 and increased plasma glucose and decreased plasma nonesterified fatty acids (NEFA) on d 7 and 13 postpartum relative to the saline group. Administration of glycerol alone increased plasma glucose on d 7 and plasma triacylglycerols on d 1 postpartum. Glycerol administration also decreased plasma glucagon and NEFA on d 1, 7, and 13 and plasma beta-hydroxybutyrate (BHBA) on d 1 postpartum relative to the saline group. Administration of glucagon plus glycerol increased and sustained concentrations of plasma glucagon, glucose, and insulin on d 1, 7, and 13 and decreased plasma NEFA on d 1, 7, and 13 and BHBA on d 1 and 7. Early postpartal treatment of dairy cows with glucagon plus glycerol increased plasma glucose and insulin, decreased plasma NEFA and BHBA, and increased secretion of liver NEFA as plasma triacylglycerols. This suggests that glucagon and glycerol, when co-administered, act to decrease the likelihood of metabolism-related syndrome development in dairy cows.
 ...
PMID:Acute metabolic responses of postpartal dairy cows to subcutaneous glucagon injections, oral glycerol, or both. 1876 90

Fish oil treatment was used in reversing the morphological and metabolic changes of C57BL/6 mice fed high-fat-high-sucrose (HFHS) diet. Two-month-old male C57BL/6 mice were fed HFHS chow or standard chow (SC). At 3 months of age, HFHS mice were separated into an untreated group (HFHS) and a group treated with fish oil (HFHS-Fo, 1.5g/kg/day). At 4 months of age, HFHS fed mice had an increase in body mass (BM) and total body fat, when the animals were sacrificed. Both parameters were lower in HFHS-Fo than in HFHS mice. Plasma glucose and insulin levels were not affected among the groups, but HFHS and HFHS-Fo animals had higher homeostasis model assessment for insulin resistance HOMA-IR ratio. HFHS and HFHS-FO mice had increased plasma total cholesterol and LDL-C, HFHS-Fo increased plasma HDL-C and decreased triglycerides levels. The liver mass (LM) and the adipocytes' size were larger in HFHS mice, while HFHS-Fo mice had a lower LM and smaller adipocytes. The liver steatosis and hepatocyte binucleation were increased in HFHS mice, while HFHS-Fo mice had reduced liver steatosis and hepatocyte binucleation. HFHS-Fo mice had a lower pancreas mass, while HFHS animals had higher islet pancreatic diameter. The SC group showed strong expression for insulin, glucagon and a glucose transporter type 2 GLUT-2 in all pancreatic islets, while in HFHS mice there was less expression for GLUT-2. However, HFHS-Fo mice showed an increase of GLUT-2 expression. In conclusion, dietary fish oil treatment reduces body mass and fat pad adiposity, and also by reducing plasma TG and pancreatic islet hypertrophy in mice fed high-fat-high-sucrose diet. Furthermore, fish oil improves glucagon and GLUT-2 expressions when it is decreased in insulin, but in hepatocyte binucleation and hepatic steatosis where the effect is reduced.
 ...
PMID:Adipose tissue, liver and pancreas structural alterations in C57BL/6 mice fed high-fat-high-sucrose diet supplemented with fish oil (n-3 fatty acid rich oil). 1918 42

The coexistence of intrauterine and neonatal malnutrition and the development of obesity, type 2 diabetes and related comorbidities have been confirmed in a number of studies in humans and animal models. Data from studies in animals suggest that epigenetic changes as a result of altered methylation of the genomic DNA may be responsible for such metabolic patterning. Methionine, an essential amino acid, plays a critical role in the methyltranferases involved in the methylation by providing the one-carbon units via the methionine transmethylation cycle. Because of its interaction with a number of vitamins (B12, folate, pyridoxine), its regulation by hormones, i.e. insulin and glucagon, and by the changes in redox state, methionine metabolism is effected by nutrient and environmental influences and by altered physiological states. In the present review the impact of human pregnancy, dietary protein restriction and fatty liver disease on methionine metabolism is discussed. The role of methionine in metabolic programming in a commonly used model of intrauterine growth retardation and in propagation of fatty liver disease is briefly described.
 ...
PMID:Metabolism of methionine in vivo: impact of pregnancy, protein restriction, and fatty liver disease. 1934 72

The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon-like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased low-density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.
 ...
PMID:Olive oil consumption and non-alcoholic fatty liver disease. 1937 Jul 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>