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Alleviation of fatty liver in dairy cows with 14-day intravenous infusions of glucagon.

Twenty multiparous cows were fed additional concentrate during the final 30 d prepartum to cause susceptibility to fatty liver. From 14 to 42 d postpartum, all cows were subjected to a protocol to induce fatty liver and ketosis. To test glucagon as a treatment for fatty liver, either glucagon at 10 mg/d or excipient was infused via the jugular vein from 21 to 35 d postpartum. All cows had fatty liver at 14 d postpartum and became ketonemic and hypoglycemic during the induction of ketosis. Glucagon increased plasma glucose to 142% of that of controls throughout the 14-d treatment. The hypoinsulinemia present in cows with fatty liver was not affected by glucagon. Plasma beta-hydroxybutyrate and nonesterified fatty acids were decreased by glucagon. At 6 d postpartum, liver triacylglycerol averaged 12.9% of liver (wet weight basis). Glucagon had decreased triacylglycerol content of livers by 71% at d 35. Glycogen was 1.0% of the wet weight of livers at 6 d in milk, but it was decreased by glucagon to 0.5% at 2 d after glucagon began. Glycogen then increased in cows treated with glucagon until at 38 d in milk liver glycogen was 3.7% versus 1.6% in controls. Our results document that glucagon decreases the degree of fatty liver in early lactation dairy cows, which also decreases the incidence of ketosis after alleviation of fatty liver.

3-Hydroxybutyric Acid↗

[Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis].

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome. Since the prevalence of obesity and consequently of the metabolic syndrome is steadily increasing, the different types of NAFLD are nowadays the most common cause of liver injury in North America. The development of NASH and fatty liver cirrhosis occurs after a "two-hit-theory", in which hepatic steatosis is followed by lipid peroxidation, the production of cytokines and the induction of Fas ligand. A standardized drug based therapy does not exist so far, but glitazones have emerged as a promising treatment option. However, since the disease is related to Western lifestyle, treatment should be based on prevention and changes in lifestyle.

Fatty Liver↗

[Experimental and clinical studies on the mechanism of alcoholic fatty liver (author's transl)].

In order to clarify the mechanism of alcoholic fatty liver, rats were reared with alcohol diet from adult, foetal or weanling periods. When rats were fed with the diet from adult for 4 weeks, these livers showed apparent fatty deposition histologically and biochemically. Low density lipoprotein (LDL) in serums of these rats lowered in level significantly than control, which indicate decreased production of secretion of very low density lipoprotein (VLDL) in the liver from which converted to LDL in peripheral tissues. When rats were reared with the diet from their foetal life, their livers deposited little of fat at any time examined after birth up to 13 weeks in spite of good diet uptake. The same phenomenon was observed in rats reared from their weanling period with the diet. In situ liver perfusion was performed to clarify the anti-fatty liver mechanism. Ketone body (KB) production rates from palmitate infused constantly at physiological concentration and bile production rates were not different among control, weanling and foetal groups. Oxygen consumption rate in control decreased after infusion of palmitate-albumin complex solution. However the rates in weanling and foetal alcohol rats increased significantly after infusion of the solution. The latter group showed more increase in rate than the former. When theoretical oxygen consumption for production of KB was compared with actual one, livers from control rats seemed to use the whole oxygen for KB production. On the other hand only 59.7% of whole oxygen in foetal alcohol group and 85.9% in weanling group used for KB production respectively. It is surmized that the increased non ketone oxygen in these groups, especially in foetal alcohol group, indicate the anti-fatty liver mechanism in these groups, probably augmented FFA oxidation. Electrophoretic analysis of lipoproteins in chronic alcoholisms showed decreased beta and pre-beta band and increased alpha band. These changes returned to normal after 1 week of admission. These experimental and clinical data indicate that impaired oxidation of FFA is an important factor for the formation of alcoholic fatty liver and impaired transport of fat from liver might enhance the change in the liver.

Adult↗

Non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects a high proportion of the world's population. Insulin resistance and oxidative stress play a critical role in the pathogenesis of NAFLD. Clinical, biochemical and imaging studies are of value in the diagnostic evaluation of patients with NAFLD, but liver biopsy remains the most sensitive and specific means of providing important diagnostic and prognostic information. Simple steatosis has the best prognosis within the spectrum of NAFLD, but NAFLD has the potential to progress to steatohepatitis, fibrosis and even cirrhosis. No effective medical therapy is currently available for all patients with NAFLD. In patients with diabetes mellitus and hyperlipidemia, appropriate metabolic control is always recommended, but rarely effective in resolving the liver disease. Weight reduction, when achieved and sustained, may improve the liver disease, although the results with weight loss have been inconsistent. Pharmacological therapy aimed at the underlying liver disease holds promise. Several medications with different mechanisms of action and potential benefit are currently being evaluated in clinical trials. Liver transplantation is a life-extending therapeutic alternative for patients with end-stage NAFLD, but NAFLD may recur after liver transplantation.

Biopsy↗

Review article: the metabolic syndrome and non-alcoholic fatty liver disease.

Metabolic syndrome represents a common risk factor for premature cardiovascular disease and cancer whose core cluster includes diabetes, hypertension, dyslipidaemia and obesity. The liver is a target organ in metabolic syndrome patients in which it manifests itself with non-alcoholic fatty liver disease spanning steatosis through hepatocellular carcinoma via steatohepatitis and cirrhosis. Given that metabolic syndrome and non-alcoholic fatty liver disease affect the same insulin-resistant patients, not unexpectedly, there are amazing similarities between metabolic syndrome and non-alcoholic fatty liver disease in terms of prevalence, pathogenesis, clinical features and outcome. The available drug weaponry for metabolic syndrome includes aspirin, metformin, peroxisome proliferator-activated receptor agonists, statins, ACE (angiotensin I-converting enzyme) inhibitors and sartans, which are potentially or clinically useful also to the non-alcoholic fatty liver disease patient. Studies are needed to highlight the grey areas in this topic. Issues to be addressed include: diagnostic criteria for metabolic syndrome; nomenclature of non-alcoholic fatty liver disease; enlargement of the clinical spectrum and characterization of the prognosis of insulin resistance-related diseases; evaluation of the most specific clinical predictors of metabolic syndrome/non-alcoholic fatty liver disease and assessment of their variability over the time; characterization of the importance of new risk factors for metabolic syndrome with regard to the development and progression of non-alcoholic fatty liver disease.

Cardiovascular Diseases↗

Immunohistochemical and biochemical studies in 4-aminopyrazolopyrimidine (4-APP)-induced fatty liver.

Four-aminopyrazolopyrimidine (4-APP)-induced fatty livers were studied immunohistochemically and biochemically. Immunohistochemical localization of glutathione-peroxidase (GSH-PO) in control rat liver was predominantly observed in the hepatocytes of portal zones of the hepatic lobules. After 3 days of 4-APP administration, the intensity of GSH-PO staining was weaker than that of control. Especially, this tendency was predominantly observed in portal zones of the hepatic lobules. Biochemcally, lipid peroxide levels measured by thiobarbituric acid method in the liver homogenates were markedly increased following 4-APP administration. However, glutathione-peroxidase (GSH-PO) activity in the same homogenates was decreased. Based on our data, we strongly suggested that pathogenesis of 4-APP induced-fatty liver may be due to uncontrolled free radical formation, peroxidation of lipids, and an associated lipid accumulation in the liver.

Animals↗

Probucol prevents the progression of fatty liver in MSG obese mice.

We investigated the effect of Probucol in preventing fatty liver in monosodium-L-glutamate (MSG) treated obese mice and control mice fed a high fat diet. MSG mice became significantly obese 9 weeks after birth with higher levels of serum blood glucose, total cholesterol, HDL-cholesterol, GPT, and cholinesterase, and had greater triglyceride contents in their livers relative to control mice. Morphologically, MSG obese mice also had a marked fatty liver. Administration of Probucol mixed with the high fat diet for 2 weeks significantly decreased the serum levels of total cholesterol and HDL-cholesterol, and liver triglyceride contents in both MSG and control mice. Morphologically, the livers were less fatty after Probucol treatment. These results suggest that Probucol prevents the development of fatty liver, and in addition reduces hypercholesterolemia.

Animals↗

Relationship between fatty liver and liver metastasis in rats given injection of rat colon cancer cell line.

BACKGROUND/AIMS: In a previous study we described that colorectal cancer patients with fatty liver had few liver metastases. To clarify whether this clinical finding is correct, we studied whether rats with fatty liver had infrequent liver metastases using experimental colon cancer. METHODOLOGY: Twenty male inbred F344/DuCrj rats (CLEA JAPAN Inc.), 8 weeks of age, were used in this study. These 20 rats were divided into two groups: Fatty liver group (FL group, n = 10) and Non-fatty liver group (NFL group, n = 10). 1.0 ml of tumor-cell suspension containing 1 x 10(7) RCN-9 cells was injected just under the capsule of the spleen. All animals were sacrificed 2 weeks after tumor inoculation. RESULTS: 1) Four rats out of 10 in the FL group (40%) had at least one metastatic nodule on the surface of the liver, while there were 10 rats with metastatic nodules in the NFL group (100%) (p < 0.01). 2) The ratio of the liver metastasis area against the largest section of the left lobe of the lateral segment (RLML) was examined. The average RLML of the FL group was 0.45%, which was significantly lower than that of the NFL group (7.11%) (p < 0.0001). CONCLUSIONS: Rats with fatty liver seldom had liver metastases compared to normal rats. This means that fatty liver itself can possibly bring about situations with infrequent liver metastases.

Animals↗

[Ultrasonic and laboratory studies on fatty liver in white-collar workers].

Ultrasonic and laboratory studies were performed in 816 white-collar workers over 35 years old who received health examination. Prevalence of fatty liver diagnosed by ultrasonography was 17.9% in all subjects and was maximum (24.4%) in males 45-49 years of age. Obesity index and body mass index were higher in fatty liver than in normal controls. Serum levels of glutamate pyruvate transaminase (GPT), cholinesterase, glutamate oxaloacetate transaminase (GOT), gamma-glutamyl transpeptidase (gamma-GTP), triglyceride, total cholesterol, uric acid, HbA1c and glucose were significantly higher, and a serum level of HDL-cholesterol was significantly lower in males with fatty liver than in controls with obesity. Prevalence of abnormal laboratory findings in fatty liver was also shown, and prevalence of fatty liver was prominently high in males with severe obesity or with mild elevation of GPT. A major cause of fatty liver was considered as obesity. In conclusion, fatty liver was a common cause of liver dysfunction and was closely related to risk factors for atherosclerosis especially in white-collar workers.

Adult↗

Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease.

In the absence of surrogate markers, the evaluation of suspected nonalcoholic fatty liver disease (NAFLD) is highly dependent on histological examination. The extent of sampling variability affecting the reliability of a single liver biopsy in patients with suspected NAFLD is poorly characterized. This prospective study aimed to correlate precise histological findings in paired biopsies--right and left lobe--in the diagnosis of NAFLD in morbidly obese subjects undergoing bariatric surgery employing both Brunt and Matteoni classifications and the NAFLD Activity Score (NAS). We also aimed to determine whether the composite histopathological findings of the two biopsies would improve diagnostic accuracy. Consecutive subjects had an intraoperative biopsy from both right and left lobes, evaluated and scored in a blinded manner. Intraobserver agreement was also assessed. Kappa coefficients of agreement were calculated. Forty-one subjects had acceptable biopsies. Agreement for steatosis was excellent and moderate for fibrosis. Concordance was only fair for most features of necroinflammation. Intraobserver agreement was only moderate for lobular inflammation. Excellent agreement was seen for the diagnosis of NASH using Brunt criteria and good agreement when using Matteoni and NAS scoring systems. Composite biopsy data particularly improved identification of hepatocyte ballooning. The diagnostic accuracy also improved substantially when composite features were compared with single-sided biopsy features, especially for the Matteoni and NAS scoring systems. In conclusion, significant sampling variability occurs in NAFLD, particularly for features of necroinflammation. This should be factored into the design of clinical trials and studies of the natural history of the disease.

Adult↗

Hepatic circulation and hepatic oxygen consumption in alcoholic and nonalcoholic fatty liver.

The purpose of this study was to determine the differences in hepatic circulation and oxygen consumption in two groups: those with nonalcoholic obesity-related fatty live and those with alcoholic fatty liver. Although the histological degree of fatty infiltration was equal in the two groups, the delta Er569-650, as an index of the regional liver blood flow estimated by spectrophotometric method, was significantly lower in alcoholic fatty liver than in nonalcoholic fatty liver, and the in vivo hepatic oxygen consumption (VO2), also determined by hepatic reflectance spectrophotometry during peritoneoscopy, tended to be lower in alcoholic fatty liver than in nonalcoholic fatty liver. The oxygen saturation of hemoglobin in local liver blood (SO2) was, however, significantly higher in alcoholic fatty liver than in nonalcoholic fatty liver. These results suggest that an increase in oxygen extraction to maintain oxygen consumption, which was indicated by the lowering of the SO2, was not found in alcoholic fatty liver, in spite of a reduction of oxygen supply to the liver. It is concluded that the impairment of hepatic circulation and hepatic oxygen consumption was more serious in alcoholic fatty liver than in nonalcoholic fatty liver, possibly contributing to a different prognosis for the two forms of fatty liver.

Fatty Liver, Alcoholic↗

The natural history of nonalcoholic fatty liver: a follow-up study.

Nonalcohol-induced fatty liver is widely believed to be a benign condition with little or no risk of disease progression. There have been occasional reports of progression to cirrhosis but none in the absence of preexisting fibrosis on the index biopsy specimen even when co-existing hepatitis was present (steatohepatitis). From our histological database (1978 to 1985), we identified 161 patients with fatty liver seen at our institution and traced the case notes of 156. One hundred five patients were initially excluded as having an alcohol-induced cause, and the remaining 51 either were seen in the clinic (37) or had died, in which cases copies of their death certificates were obtained (14). A further 7 patients were excluded after clinic attendance gave evidence of alcohol excess and another 4 after review of their initial biopsy showed the presence of fibrosis or steatohepatitis. The apparent cause of the steatosis in the 40 included patients with strictly nonalcohol-induced pure fatty liver was obesity in 12, diabetes in 4 (1 obese patient), and cachexia associated with extrahepatic malignancy in 6. Four of the remaining 19 had serological evidence of an autoimmune disorder, but none of these had any clinical or histological features of autoimmune liver disease. Nine patients had evidence of hyperlipidemia, 3 of whom were also obese. At a median follow-up of 11 years (7 to 16), 12 of 26 living patients had abnormal results of liver blood tests and had repeat liver biopsies performed. None had progressed to steatohepatitis or cirrhosis; 1 obese patient had developed mild fibrosis 9.8 years after her index biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of dietary hyperlipidemic components and fish oil on concentration of lipids in liver and liver fatty acid profile of rats.

This investigation was attempted to clarify the effects of dietary hyperlipidemic components and fish oil on concentration of lipids in liver and liver fatty acid profile of rats. In a first experiment male Sprague-Dawley rats were maintained on a semipurified low-fat diet with 6.5% coconut oil and 1.5% safflower oil, but without added cholesterol, or a high-fat hyperlipidemic diet supplemented with 7.3% coconut oil, 7.3% beef tallow, 0.4% safflower oil, and 1.5% cholesterol for 28 days. Rats fed the hyperlipidemic diet were then switched to fish oil diets with 1.4%, 2.8%, and 5.6% fish oil in exchange for coconut oil and beef tallow for, respectively, 10 and 20 days. In a second experiment male Sprague-Dawley rats were fed low-fat or high-fat diets without or with 1.5% added cholesterol for 28 days. Half of each group was then changed to a fish oil diet (for 20 days) which contained 5.6% fish oil in exchange for coconut oil and beef tallow. In experiment 1, rats fed the hyperlipidemic diet had enlarged fatty livers within 28 days. Experiment 2 showed that cholesterol in the diet was responsible for the accumulating liver lipids. Feeding diets with added cholesterol, the proportions of saturated fatty acids (SFA), especially 18:0, were markedly reduced in liver, whereas levels of monounsaturated fatty acids (MUFA) were greatly increased compared to diets without added cholesterol. This increase was most pronounced with respect to 16:1 and 18:1. In contrast, fish oil diets lowered MUFA level in liver in spite of its high MUFA content. Rats fed the highly saturated hyperlipidemic diet low in 18:2 n-6 had reduced 18:2 n-6 levels in liver compared to rats fed the low-fat diet without added cholesterol. Also, 20:4 n-6 level in liver was markedly reduced after the administration of the hyperlipidemic diet or the fish oil diets. Results of experiment 2 elucidate that cholesterol as well as fish oil sharply lowered 20:4 n-6 level in liver, which might be due to a reduced desaturation. In both experiments feeding fish oil increased all long-chain n-3 polyunsaturated fatty acids (PUFA) in liver. This occurred in a dose-dependent fashion and reached a maximum level with 5.6% fish oil in the diet. When additional cholesterol was applied 22:6 n-3 level in liver fell. This indicates also an impaired desaturation of PUFA due to dietary cholesterol.

Animals↗

Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease.

BACKGROUND/AIMS: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. METHODS AND RESULTS: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P < 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P < 0.01) compared with those with homeostasis model of insulin resistance below the median. CONCLUSIONS: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.

Adult↗

A comparison study of ultrasound and Xenon-133 hepatic retention ratio in fatty liver.

BACKGROUND/AIMS: We compared ultrasound and Xenon-133 hepatic retention ratio to evaluate the accuracy of ultrasound in diagnosing fatty liver. METHODOLOGY: One hundred and forty-six patients with suspected fatty liver were included. All patients underwent an ultrasound study followed by a determination of the Xenon-133 hepatic retention. RESULTS: Using the Xenon-133 hepatic retention ratio as the diagnostic standard, the overall accuracy of ultrasound in detecting fatty liver was 57.5%, with 100% sensitivity and 6.0% specificity. CONCLUSIONS: Ultrasound can be used as a first-line screening imaging modality for fatty liver. If the result of ultrasound is equivocal, then Xenon-133 hepatic retention determination should be performed for the diagnosis and management of fatty liver.

Adult↗

Avian fatty liver hemorrhagic syndrome: a comparative review.

Metabolic fatty liver syndromes occur in a variety of species including chickens, humans, cows, and cats. Both energy excess and deficit appear to initiate the accumulation of liver fat. Although the conditions preceding the onset of liver steatosis vary, all syndromes share a common basis in altered lipid utilization, lipoprotein assembly, and secretion. Laying hens and humans appear to develop fatty livers under similar metabolic conditions of energy excess. This similarity and the additional structural requirements inherent in yolk deposition make the laying hen an exciting model in which to study lipoprotein synthesis, assembly, and secretion. The overfed hen provides additional insights into the effects of nutrition and hormones on these same processes. Within this model it may be possible to distinguish the effects of altered gene expression versus altered physical properties (lipids) and postranslational processing (proteins) in mediating the observed responses.

Animals↗

Nonalcoholic fatty liver disease decrease in obese adolescents after multidisciplinary therapy.

BACKGROUND: Despite the increasing prevalence of nonalcoholic fatty liver disease, its pathogenesis and clinical significance remain poorly defined and there is no ideal treatment. OBJECTIVE: The aim of this study was to assess the short-term (12-week) multidisciplinary therapy on visceral adiposity and nonalcoholic fatty liver disease control. METHODS: We evaluated and compared the distribution of visceral adiposity and nonalcoholic fatty liver disease, by ultrasonography, in 73 post-puberty obese participants (17.01+/-1.6 years old; body mass index 36.54+/-2.86 kg/m), submitted to a multidisciplinary treatment without medications, at the beginning and after 12 weeks of intervention. Descriptive and one-way analysis of variance, and paired t-test were performed. RESULTS: The results indicated that after intervention the adolescents had a significant reduction in visceral adiposity (4.05+/-1.55 to 3.37+/-1.44) and nonalcoholic fatty liver disease prevalence (from 52 to 29% on the right side and from 48 to 29% on the left side). It is a positive result because nonalcoholic fatty liver disease can progress to cirrhosis, even in children and adolescents. CONCLUSIONS: The short-term treatment suggests a profound impact on the control of obesity-related co-morbidities in young people.

Adiposity↗

Serum magnesium levels in patients with alcoholic and non-alcoholic fatty liver.

INTRODUCTION: Magnesium is currently a subject of major interest in biology and medicine. Magnesium is intimately involved in over 300 enzymatic reactions. particularly in processes involving the formation and utilization of ATP. It is known that alcoholism is connected with hypomagnesemia. There are also several studies describing the disorders of magnesium balance in patients with liver diseases. THE AIM OF STUDY: was to investigate the serum magnesium levels in patients with liver steatosis. We compared the magnesium levels in patients with non-alcoholic and alcoholic fatty liver to estimate if alcoholism is the only cause of magnesium disorders or if also liver function disorders play any role in the development of magnesium dysbalance in patients with liver steatosis. PATIENTS AND METHODS: The studied group consisted of 44 patients with hepatic steatosis (25 non-alcoholic and 19 alcoholic). The control group consisted of 57 healthy subjects. Magnesium levels were assayed by atomic absorption spectrometry. RESULTS: Serum magnesium levels were significantly decreased in patients with alcoholic (0.67 +/- 0.10 vs 1.02 +/- 0.11 mmol.l(-1)) and also in patients with non-alcoholic liver steatosis (0.65 +/- 0.14 vs 1.02 +/- 0.11 mmol.l(-1)). There were also moderately increased activities of aminotransferases and gamma-glutamyltransferase. Plasma triacylglycerols were increased in both studied groups. Albumin and prealbumin levels were not changed in comparison to the control group. There was a slight increase in plasma levels of immunoglobulin A and immunoglobulin G. CONCLUSIONS: The results of our study showed hypomagnesemia in both studied groups. Decreased magnesium levels found also in patients with non-alcoholic fatty liver suggest that alcoholism cannot be the only cause of hypomagnesemia in patients with fatty liver. Hypomagnesemia is not only a laboratory symptom of fatty liver but due to its connection with increased oxidative stress it might be a risk factor in the progression of fatty liver to steatohepatitis (Tab. 3, Ref: 19).

Adult↗