Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FATTY LIVER”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed2005

[Effects of metformin on fatty liver in insulin-resistant rats].

OBJECTIVES: To investigate the effects of metformin on fatty livers in insulin-resistant rats. METHODS: Thirty-one male Wistar rats were randomly divided into a normal (n=8) and an experimental group (n=23). The normal group rats were fed a standard diet, and those of the experimental group with a high-fat diet. After 8 weeks, 7 rats from the experimental group were sacrificed to verify whether the model was established successfully. Then the experimental group was randomly subdivided into two groups: one with metformin treatment (n=8) and one without (n=8). After 6 weeks, insulin sensitivity was measured with glucose infusion rate (GIR) by euglycermic hyperinsulinemia clamp technique. Aminotransferase, triglyceride (TG) and free fatty acids (FFA) were measured by biochemical methods, insulin by radioimmunoassay and tumor necrosis factor-alpha (TNF alpha) by ELISA. The steatosis changes and inflammation activity of all rat livers were scored histologically. RESULTS: Compared with the model group, the insulin resistance, liver index, visceral adiposity and weight loss of the metformin group were dramatically ameliorated. The steatosis and the inflammatory activity in the livers and the level of serum aminotransferase of the metformin group were also significantly decreased. Furthermore, metformin treatment lowered serum TG, liver lipid accumulation and the production of FFA and TNF alpha. CONCLUSION: Metformin can significantly improved insulin resistance and fatty liver development in rats fed a high-fat diet. It may become a new choice for fatty liver treatment in the future.

Animals↗
PubMed1987

Effect of liver fatty acid binding protein on fatty acid movement between liposomes and rat liver microsomes.

Although movement of fatty acids between bilayers can occur spontaneously, it has been postulated that intracellular movement is facilitated by a class of proteins named fatty acid binding proteins (FABP). In this study we have incorporated long chain fatty acids into multilamellar liposomes made of phosphatidylcholine, incubated them with rat liver microsomes containing an active acyl-CoA synthetase, and measured formation of acyl-CoA in the absence or presence of FABP purified from rat liver. FABP increased about 2-fold the accumulation of acyl-CoA when liposomes were the fatty acid donor. Using fatty acid incorporated into liposomes made either of egg yolk lecithin or of dipalmitoylphosphatidylcholine, it was found that the temperature dependence of acyl-CoA accumulation in the presence of FABP correlated with both the physical state of phospholipid molecules in the liposomes and the binding of fatty acid to FABP, suggesting that fatty acid must first desorb from the liposomes before FABP can have an effect. An FABP-fatty acid complex incubated with microsomes, in the absence of liposomes, resulted in greater acyl-CoA formation than when liposomes were present, suggesting that desorption of fatty acid from the membrane is rate-limiting in the accumulation of acyl-CoA by this system. Finally, an equilibrium dialysis cell separating liposomes from microsomes on opposite sides of a Nuclepore filter was used to show that liver FABP was required for the movement and activation of fatty acid between the compartments. These studies show that liver FABP interacts with fatty acid that desorbs from phospholipid bilayers, and promotes movement to a membrane-bound enzyme, suggesting that FABP may act intracellularly by increasing net desorption of fatty acid from cell membranes.

Acyl Coenzyme A↗
PubMed2006

Mouse models in non-alcoholic fatty liver disease and steatohepatitis research.

Non-alcoholic fatty liver disease (NAFLD) represents a histological spectrum of liver disease associated with obesity, diabetes and insulin resistance that extends from isolated steatosis to steatohepatitis and cirrhosis. As well as being a potential cause of progressive liver disease in its own right, steatosis has been shown to be an important cofactor in the pathogenesis of many other liver diseases. Animal models of NAFLD may be divided into two broad categories: those caused by genetic mutation and those with an acquired phenotype produced by dietary or pharmacological manipulation. The literature contains numerous different mouse models that exhibit histological evidence of hepatic steatosis or, more variably, steatohepatitis; however, few replicate the entire human phenotype. The genetic leptin-deficient (ob/ob) or leptin-resistant (db/db) mouse and the dietary methionine/choline-deficient model are used in the majority of published research. More recently, targeted gene disruption and the use of supra-nutritional diets to induce NAFLD have gained greater prominence as researchers have attempted to bridge the phenotype gap between the available models and the human disease. Using the physiological processes that underlie the pathogenesis and progression of NAFLD as a framework, we review the literature describing currently available mouse models of NAFLD, highlight the strengths and weaknesses of established models and describe the key findings that have furthered the understanding of disease pathogenesis.

Adipose Tissue↗
PubMed2005

The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies.

BACKGROUND/AIMS: The histological course of nonalcoholic fatty liver disease (NAFLD) remains undescribed. Therefore, we examined the liver histology of NAFLD patients who had undergone sequential liver biopsies. METHODS: Data on 103 patients who underwent serial liver biopsies in the absence of effective treatment were reviewed, and biopsies scored in a blind fashion. RESULTS: Mean interval between biopsies was 3.2+/-3.0 years (range 0.7-21.3). Fibrosis stage apparently progressed in 37%, remained stable in 34% and regressed in 29%. Severity of steatosis, inflammation, hepatocyte ballooning and Mallory's hyaline improved significantly. Aminotransferases decreased significantly between biopsies, paralleling improvement in steatosis and inflammatory features but not fibrosis stage. The rate of fibrosis change ranged from -2.05 to 1.7 stages/year. By multivariate analysis, diabetes (P = 0.007) and low initial fibrosis stage (P < 0.001) were associated with higher rate of fibrosis progression, as was higher body mass index (P = 0.008) when cirrhotics were excluded. CONCLUSIONS: Fibrosis in NAFLD progresses slowly over time with considerable variability in the rate of changes among patients. Changes of aminotransferases do not parallel changes in fibrosis stage. Diabetic patients with elevated BMI and low fibrosis stage are at risk for higher rates of fibrosis progression.

Adult↗
PubMed2006

New treatments for nonalcoholic fatty liver disease.

The majority of patients with nonalcoholic fatty liver disease are overweight and obese, lead relatively sedentary lifestyles, and have underlying insulin resistance. Treatment aimed at improving body weight and activity should be the cornerstone of our therapeutic armamentarium in combating this disease. Evidence suggests that diets low in processed carbohydrates and saturated fats with a goal to achieve a 500- to 1000-calorie/day deficit improve insulin sensitivity, reduce serum aminotransferases, and decrease hepatic steatosis. Encouragingly, improvements are seen with as little as a 5% reduction in body weight. Histopathologic parameters of steatohepatitis also appear to improve with weight loss. Antioxidant supplementation, specifically with vitamin E, may be considered as adjunctive therapy. Other antioxidants and the thiazolidinediones (pioglitazone and rosiglitazone) appear to be efficacious, but larger confirmatory studies are needed to ensure they are safe and beneficial in patients with nonalcoholic steatohepatitis. Novel agents such as renin-angiotensin system inhibitors may eventually prove to be efficacious as well. Future treatment for patients failing to achieve weight loss goals is likely to consist of combination therapy targeting insulin resistance, oxidative stress, and fibrogenesis.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Decreased prevalence of nonalcoholic fatty liver disease in black obese children.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a common cause of pediatric liver disease. Studies suggest decreased prevalence in blacks, females, and younger children. However, the proportion of black subjects in these studies was small, and children under 12 were not included. We propose that abnormal alanine aminotransferase (ALT) is more common in whites than blacks, males than females, and children over 12 compared with younger children in a prospective study. METHODS: We enrolled 181 consecutive asymptomatic obese children attending general pediatric clinics who denied recent fever or known liver disease. Obesity was defined as body mass index (BMI) z score of greater than 1.64 (95th percentile for age and sex). Elevated ALT was defined as greater than 40 U/L. BMI z score, race, sex, age, and parental obesity were compared using the chi-square test and Fisher's exact test. RESULTS: The population included 81 males and 100 females, 147 non-Hispanic black, 33 non-Hispanic white, and 1 Hispanic white. Elevated ALT occurred in 14 (8%) subjects. White children were significantly more likely to have abnormal ALT (odds ratio [OR] = 4.0, P < .02). Very obese children (BMI z score >2.3) were more likely to have abnormal ALT compared with mildly obese children (OR = 4.0, P < 0.05). Sex, age, hepatomegaly, acanthosis nigricans, and parental obesity did not significantly predict elevated ALT. CONCLUSION: Eight percent of asymptomatic, obese children had an elevated ALT suggestive of NAFLD. White and very obese children are more likely to be affected. Sex and age are not good clinical predictors of NAFLD. We suggest that all obese children be screened for NAFLD.

Adolescent↗
PubMed2005

Hypoadiponectinemia and insulin resistance are associated with nonalcoholic fatty liver disease.

We investigated the association between nonalcoholic fatty liver disease (NAFLD) and plasma adiponectin levels and insulin resistance. We recruited study subjects among one hundred and eighty one persons who were examined abdominal ultrasound at routine screening tests. A standard interview (consumption of alcohol and medical history), physical examination (height, weight, waist circumference, and blood pressure), and biochemical study (lipid parameters, aminotransferases, fasting plasma glucose, fasting insulin, and plasma adiponectin) were performed. Subjects who consumed alcohol more than moderate, evidence of viral hepatitis, toxic hepatitis, and serious cardiac, renal, or hepatic disease were excluded. Thirty-eight NAFLD patients and 53 control subjects diagnosed by ultrasound were finally analyzed. The plasma adiponectin level was significantly correlated with HDL-cholesterol (r=0. 38, p<0.001), triglycerides (r=-0.22, p=0.04), fasting insulin (r=-0.37, p<0.01), and insulin resistance by homeostasis model of assessment-insulin resistance (HOMAIR) (r=-0.39, p<0.01), after adjusting for age, sex, and adiposity. Multiple logistic regression analysis indicated that HOMA-IR was a significant predictor of having NAFLD (odds ratio [OR]=2.38; 95% confidence interval [CI]: 1.52-5.74), while adiponectin had a protective effect against NAFLD (OR=0.22; 95% CI: 0.09-0.55). We demonstrated that hypoadiponectinemia and insulin resistance are associated with NAFLD independent of obesity.

Adiponectin↗
PubMed2006

Familial aggregation of insulin resistance in first-degree relatives of patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: An association between nonalcoholic fatty liver disease (NAFLD) and the insulin resistance (IR) syndrome exists. Familial clustering of IR may support a genetic predisposition to NAFLD or cryptogenic cirrhosis (CC). METHODS: Patients with NAFLD (n = 20) and healthy controls (n = 20) matched for age, sex, and body mass index with at least 4 living relatives and 2 generations of lineage participated in a familial aggregation study. A medical history was obtained from each subject and confirmed with first-degree family members. RESULTS: NAFLD patients were more likely to have cirrhosis (odds ratio [OR] = 12.0), cardiac disease (OR, 3.0), hyperlipidemia (OR, 12.1), diabetes mellitus (DM) (OR, 9.1), renal stones (OR, 4.1), and arthritis (OR, 6.1). IR (P = .042) (the primary dependent variable) and DM (P = .013) were noted in their first-degree relatives. A trend for familial clustering of NAFLD or CC (P = .059) with a maternal linkage for disease expression also may exist. Cholelithiasis (P = .047), presumed NAFLD and/or CC (P = .049), and a trend toward IR (P = .07) were noted in the mothers, but not the fathers, of patients with NAFLD. An increased risk of DM (OR, 4.2; 95% confidence interval, 1.26-18.7; P = .013), IR (OR, 2.86; 95% confidence interval, 1.02-9.38; P = .042), and smoking (OR, 3.41; 95% confidence interval, 1.43-9.07; P = .003) was observed in first-degree relatives of NAFLD patients. No significant survival difference was observed between family cohorts. CONCLUSIONS: Familial clustering and a potential maternal linkage for IR support a genetic predisposition for NAFLD. Alternatively, the presence of suppressor genes modifying the expression of IR in paternal lineage warrants further investigation.

Adult↗
PubMed1998

Comparisons of the effects of temperature on the liver fatty acid binding proteins from hibernator and nonhibernator mammals.

Hibernating mammals rely heavily on lipid metabolism to supply energy during hibernation. We wondered if the fatty acid binding protein from a hibernator responded to temperature differently than that from a nonhibernator. We found that the Kd for oleate of the liver fatty acid binding protein (1.5 microM) isolated from ground squirrel (Spermophilus richardsonii) was temperature insensitive over 5-37 degrees C, while the rat liver fatty acid binding protein was affected with the Kd at 37 degrees C being about half (0.8 microM) that found at lower temperatures. This same trend was observed when comparing the specificity of various fatty acids of differing chain length and degree of unsaturation for the two proteins at 5 and 37 degrees C. At the lower temperature, ground squirrel protein bound long-chain unsaturated fatty acids, particularly linoleate and linolenate, at least as well as at the higher temperature and matched requirements for these fatty acids in the diet. The most common long-chain fatty acid, palmitate, was a more effective ligand for ground squirrel liver fatty acid binding protein at 5 degrees C than at 37 degrees C, with the opposite occurring in the eutherm. Rat protein was clearly not adapted to function optimally at temperatures lower than the animal's body temperature.

Animals↗
PubMed2006

Nonalcoholic fatty liver disease and obesity.

PURPOSE: The aim of this review is to update concepts of the nonalcoholic fatty liver disease (NAFLD) and to establish a relationship between this condition and obesity. METHODS: By means of a comprehensive literature review where special attention was devoted to articles published in the last 5 years, NAFLD is discussed in view of new concepts, diagnosis, staging, and treatment. RESULTS: NAFLD is emerging as one of the main causes of chronic liver disease and it is believed to be the hepatic component of the metabolic syndrome, whose central features include obesity, hyperinsulinemia, peripheral insulin resistance, diabetes, dyslipidemia, and hypertension. The surgical treatment of morbid obesity is one of the options available for the treatment of NAFLD. CONCLUSION: Nonalcoholic fatty liver disease is strongly related with obesity.

Adult↗
PubMed1982

Persistent transaminasemia and fatty liver. Their use in the diagnosis of presymptomatic Wilson's disease.

A 41/2-year-old asymptomatic girl with persistent elevated serum transaminase levels for eight months was found to have Wilson's disease. The diagnosis was suspected by the presence of fatty liver and nonspecific chronic hepatitis on liver biopsy and was proved by studies of copper metabolism, including determinations of serum ceruloplasmin and hepatic copper concentrations. Unexplained persistent transaminase elevation in children demand investigation by needle liver biopsy. Th presence of fatty liver and hepatitis should raise the possibility of Wilson's disease, which may then be confirmed by more specific tests. Advantages to early diagnosis include the institution of specific therapy and prevention of progressive liver disease.

Biopsy, Needle↗
PubMed1988

Computed tomography in acute fatty liver of pregnancy.

A case of the diagnosis of acute fatty liver of pregnancy proved by biopsy is described. In this case computed tomography showed decreased attenuation over the liver, and this attenuation is compatible with fatty infiltration. Computed tomography may be useful in the differential diagnosis of jaundice in pregnancy.

Acute Disease↗
PubMed2006

Nonalcoholic fatty liver disease treated by gastroplasty.

Nonalcoholic steatohepatitis (NASH), which is the most severe histologic form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in obese patients. The prevalence of NASH may increase with the rise in the rate of obesity and metabolic syndrome in affluent communities. The aim of this work is to describe clinical and histopathologic findings and correlate liver tissue damage to the length of duration of the obesity in the group of patients who underwent surgery as obesity treatment. Eighty-seven severely or morbidly obese patients underwent gastroplasty. Each patient was evaluated with complete clinical and laboratory medical assessment together with wedge liver biopsy taken from 59 unselected patients during the surgery. Patients were followed up for 41 months. Repeat liver biopsy was taken from 10 patients. Pathologic analysis recorded the presence and degree of steatosis, portal and lobular inflammation and fibrosis. Age, body mass index (BMI), and laboratory assessment correlated with pathologic data. Male patients showed more pronounced metabolic syndrome and fatty liver damage. Patients who become obese in childhood or as teenagers showed no differences in metabolic syndrome and NAFLD in mature age. There was statistically significant association between BMA, elevated transaminases, NAFLD, and fibrosis. Significant weight reduction was observed within first year after surgery, was slower in the second year, and stabilized within third year. Remarkable improvement followed in biological markers of metabolic syndrome. Ninety-six percent of initial liver biopsies had steatosis; 16% developed steatohepatitis and mild perivenular fibrosis. Significant improvement of the degenerative and inflammatory hepatic lesions in repeated biopsies and liver function readings was noted within 8 months after surgery. Obesity is a major and independent risk factor for the metabolic syndrome, NAFLD, NASH, and fibrosis. Surgical treatment improves metabolic abnormalities and hepatic lesions in long-term observations.

Adult↗
PubMed1995

The activity of lecithin:cholesterol acyltransferase in the serum of cows at parturition or with fatty liver.

The activity of lecithin:cholesterol acyltransferase (LCAT), which is responsible for esterification of plasma cholesterol, was evaluated in bovine serum. It was associated with the high-density lipoprotein fraction that contains apolipoprotein A-I, an activator of LCAT. In lactating cows, the activity was around 1000 U (decrease in nmol of free cholesterol per h per ml of serum), slightly higher than in 1-month-old calves. LCAT activity decreased around parturition, at which the time the serum concentrations of cholesteryl esters and free cholesterol were concomitantly decreased. A reduced LCAT activity was also found in cows with fatty livers induced by the administration of ethionine. In the cows with fatty livers, the serum concentration of cholesteryl esters was markedly decreased, whereas that of free cholesterol was only slightly decreased, thereby increasing the free- to esterified-cholesterol ratio. These results suggest that the decrease in LCAT activity may be involved in the reduction in fertility associated with fatty liver because esterification of cholesterol by LCAT is essential for its transport from the liver to peripheral tissues, such as the corpus luteum, and because cholesterol serves as the source of progesterone synthesis in the latter organ.

Animals↗
PubMed1988

Fatty liver in dairy cows.

An increase in liver fat concentration during the peripartum period is extremely common in dairy cows and, to some degree, is probably normal. When severe, it is associated with clinical problems including increased morbidity and mortality and reduced breeding efficiency. Fatty liver develops when serum NEFA concentrations rise and hepatic uptake of NEFA exceeds the liver's ability to synthesize and secrete lipoproteins. In most cases, hepatic lipid accumulation appears to commence prepartum, in association with rising serum NEFA concentrations and declining serum lipoprotein concentrations. Commonly used clinicopathologic tests of liver function do not yield clearly abnormal results except in animals with extremely high concentrations of liver fat. Clinically useful estimates of hepatic lipid concentration can be obtained in the field by determining the buoyancy of needle biopsy samples in liquids of various specific gravities. Clinically ill animals with liver fat concentrations of greater than 35 per cent by weight have a poor prognosis, and those that do survive will have a protracted convalescence. Treatment of dairy cows with clinical fatty liver should be aimed at reducing further adipose lipid mobilization and promoting hepatic lipoprotein synthesis; however, protocols for therapy have not as yet been evaluated critically. Prevention of fatty liver is more rewarding than treatment. Dry cows should be maintained in a moderately fat condition and fed high-quality, palatable feeds in amounts necessary to met or slightly exceed their energy requirements. Free-choice feeding of high-energy feeds should be avoided in late lactation and during the nonlactating period.

Animals↗
PubMed1999

Fatty liver--an additional and treatable feature of the insulin resistance syndrome.

To test the hypothesis that fatty liver coexists with other metabolic abnormalities of the insulin resistance syndrome, and responds to their amelioration, we prospectively studied 48 consecutive patients with chronically elevated liver enzymes and clinical, ultrasound and histological findings consistent with fatty infiltration of the liver. Most of the patients were overweight or obese (64%) with increased waist circumference which closely relates to visceral fat. Only 10% of the patients had normal glucose tolerance: 44% had diabetes mellitus, 29% impaired glucose tolerance, and 17% were hyperinsulinaemic. The most common dyslipidaemia found was hypertriglyceridaemia and/or low HDL-C (86%). Dietary intervention and follow-up (median 24 months), supplemented by oral hypoglycaemic or lipid-lowering drugs as needed, resulted not only in weight loss (mean 3.7 kg), decreased fasting blood glucose (p < 0.005) and improvement in serum lipid profile (p < 0.02 for both triglycerides or HDL-C) but also in an improvement of serum liver enzymes in 96%, which became normal in more than half of the patients. Thus, fatty liver was strongly associated with many features of the insulin resistance syndrome, and follow-up revealed a high potential for reversibility and a benign course.

Alanine Transaminase↗
PubMed1985

Ultrastructural studies in 4-aminopyrazolopyrimidine (4-APP)-induced fatty liver.

Ultrastructural alterations of 4-aminopyrazolopyrimidine (4-APP)-induced fatty liver were studied. Light microscopically, liver sections after 3 to 5 days of 4-APP administration demonstrated more extensive fatty changes and highly osmiophilic lipid droplets were mainly observed in the portal zones of the lobules. The most striking ultrastructural alterations were seen in the Golgi complexes and rough endoplasmic reticulum. Golgi complexes were markedly dilated and osmiophilic vesicles were noted near the Golgi complexes. In the rough endoplasmic reticulum, dilatation of cisternae, loss of the parallel arrangement and dilated vesicles, most of which contained diminished numbers of ribosomes, were also seen. In addition, degranulation of rough endoplasmic reticulum was observed. However, no remarkable changes were noted in the mitochondria. Based on these findings, the functional state of the organellae concerned was discussed.

Adenine↗