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

Liver fatty acid-binding protein (LFABP) is an abundant protein in hepatocytes that binds most of the long chain fatty acids present in the cytosol. It is suggested to be of importance for fatty acid uptake and utilization in the hepatocyte. In the present study, the effects of bovine GH (bGH) and other hormones on the expression of LFABP and its messenger RNA (mRNA) were studied in hypophysectomized rats and in vitro using primary cultures of rat hepatocytes. One injection of bGH increased LFABP mRNA levels about 5-fold after 6 h, but there was no effect of this treatment on LFABP levels. However, 7 days of bGH treatment increased both LFABP mRNA and LFABP protein levels 2- to 5-fold. Female rats had higher levels of LFABP than male rats. Hypophysectomy of female rats, but not that of male rats, decreased LFABP levels markedly. Treatment of hypophysectomized rats with bGH for 7 days as two daily injections or as a continuous infusion increased LFABP levels to a similar degree. This finding indicates that the sex difference in the expression of LFABP is not regulated by the sexually dimorphic secretory pattern of GH. Neither insulin nor insulin-like growth factor I treatment of hypophysectomized rats for 6-7 days had any effect on LFABP mRNA or LFABP levels. In vitro, bGH dose-dependently increased the expression of LFABP mRNA, but only in the presence of insulin. Insulin alone had a marked dose-dependent effect on LFABP mRNA levels and was of importance for maintaining the expression of LFABP mRNA during the culture. Incubation with bGH increased LFABP mRNA levels within 3 h. GH had no effect on LFABP mRNA levels in the presence of actinomycin D, indicating a transcriptional effect of GH. Incubation with glucagon in vitro decreased LFABP mRNA levels markedly, indicating that glucagon, in contrast to GH, has an effect opposite that of insulin on LFABP mRNA expression. It is concluded that GH is an important regulator of LFABP in vivo and in vitro. In contrast to the effect of GH on insulin-like growth factor I mRNA, the presence of insulin was a prerequisite for the effect of GH on LFABP mRNA expression in vitro. The results emphasize the role of GH in the regulation of hepatic fatty acid metabolism.
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PMID:Hormonal regulation of liver fatty acid-binding protein in vivo and in vitro: effects of growth hormone and insulin. 960 75

Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPalpha, PPARgamma, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFalpha were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans.
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PMID:Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. 978 93

A girl with partial lipodystrophy is described presenting with muscle weakness and developmental delay several years before lipoatrophy became apparent. The patient subsequently developed epilepsy, fatty liver, secondary amenorrhoea, hirsutism, insulin-resistant diabetes mellitus, hyperlipidaemia, and hypothyroidism. She remains weak with poor exercise tolerance. This case illustrates an atypical presentation of the Barraquer-Simon syndrome.
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PMID:Partial lipodystrophy presenting with myopathy. 1007 99

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.
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PMID:Fatty liver--an additional and treatable feature of the insulin resistance syndrome. 1020 58

The effects of glucagon infusions on expression of mRNA for enzymes that regulate gluconeogenesis were studied in lactating cows. Normal cows and cows with fatty liver that were susceptible to ketosis were assigned to either glucagon-treated or control groups. Glucagon at 0 or 10 mg/d was infused for 14 d beginning at d 21 postpartum. In normal cows, glucagon infusions increased concentrations of both plasma glucagon and glucose, which caused plasma insulin to increase. Consequently, hepatic phosphoenolpyruvate carboxykinase mRNA decreased during wk 1 of glucagon infusions. Glucagon infusions into cows with fatty liver also increased plasma glucagon and glucose, but concentrations of plasma insulin and hepatic phosphoenolpyruvate carboxykinase mRNA did not change. More phosphoenolpyruvate carboxykinase mRNA was present in the livers of cows with fatty liver than in livers of normal cows. In a follow-up experiment with midlactation cows, 3.5-h infusions of glucagon at 14 mg/d increased plasma glucose and insulin and decreased plasma nonesterified fatty acids and hepatic glycogen. Hepatic phosphoenolpyruvate carboxykinase mRNA was decreased 41%, pyruvate carboxylase mRNA was increased 50%, but fructose-1,6-bisphosphatase mRNA did not change. We conclude that the expression of the hepatic phosphoenolpyruvate carboxykinase gene in normal cows is inhibited by insulin to balance elevated carbohydrate status during glucagon infusions; however, inhibited expression of hepatic phosphoenolpyruvate carboxykinase mRNA probably is not involved in the pathogenesis of lactation ketosis.
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PMID:Regulation of messenger ribonucleic acid expression for gluconeogenic enzymes during glucagon infusions into lactating cows. 1038 1

In dairy cows, overfeeding during the dry period leads to overcondition at calving and to depression of appetite after calving. As a consequence, at calving overconditioned high-producing dairy cows inevitably go into a more severe negative energy balance (NEB) postpartum than cows that have a normal appetite. During the period of NEB, the energy requirements of the cow are satisfied by lipolysis and proteolysis. Lipolysis results in an increased concentration of non esterified fatty acids (NEFA) in the blood. In the liver, these NEFA are predominantly esterified to triacylglycerols (TAG) that are secreted in very low density lipoproteins (VLDL). In early lactation in cows with a severe NEB, the capacity of the liver to maintain the export of the TAG in the form of VLDL in balance with the hepatic TAG production is not always adequate. As a result, the excess amount of TAG accumulates in the liver, leading to fatty infiltration of the liver (hepatic lipidosis or fatty liver). The NEB and/or fatty liver postpartum are frequently associated with postparturient problems. In general, a severe NEB induces changes in biochemical, endocrinological, and metabolic pathways that are responsible for production, maintenance of health, and reproduction of the postparturient dairy cow. These changes include a decrease in blood glucose and insulin concentrations, and an increase in blood NEFA concentrations. High NEFA concentrations caused by intensive lipolysis are accompanied by impairment of the immune system, making the cows more vulnerable to infections. Metabolic diseases such as ketosis, milk fever, and displaced abomasum are related to overcondition at calving. The changes in biochemical, endocrinological, and metabolic pathways are associated with delay of the first visible signs of oestrus, an increase in the interval from calving to first ovulation, a decrease in conception rate, and a prolonged calving interval. It is possible that the increased blood NEFA concentration directly impairs ovarian function.
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PMID:Relationship between overfeeding and overconditioning in the dry period and the problems of high producing dairy cows during the postparturient period. 1042 30

The mouse fatty liver dystrophy (fld) mutation is characterized by transient hypertriglyceridemia and fatty liver during the neonatal period, followed by development of a peripheral neuropathy. To uncover the metabolic pathway that is disrupted by the fld mutation, we analyzed the altered pattern of gene expression in the fatty liver of fld neonates by representational difference analysis of cDNA. Differentially expressed genes detected include a novel member of the Ras superfamily of small GTP-binding proteins, a novel Ser/Thr kinase, and several actin cytoskeleton-associated proteins including actin, profilin, alpha-actinin, and myosin light chain. Because these proteins have a potential functional link in the propagation of hormone signals, we investigated cytoskeleton dynamics in fld cells in response to hormone treatment. These studies revealed that preadipocytes from fld mice exhibit impaired formation of actin membrane ruffles in response to insulin treatment. These findings suggest that the altered mRNA expression levels detected in fld tissue represent a compensatory response for the nonfunctional fld gene and that the fld gene product may be required for development of normal insulin response.
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PMID:Altered gene expression pattern in the fatty liver dystrophy mouse reveals impaired insulin-mediated cytoskeleton dynamics. 1043 76

The association of several risk factors, obesity, dyslipoproteinemia, hepatic steatosis, insulin resistance and hypertension with Type 2 (non-insulin-dependent) diabetes mellitus and myocardial infarction has long been known and has been termed the "metabolic syndrome". In 1988 Reaven introduced syndrome X as the link between insulin resistance and hypertension. It has been suggested that a critical factor in the association between obesity, Type 2 diabetes and cardiovascular morbidity is the mass of intraabdominal fat. Striking similarities exist between the metabolic syndrome and untreated growth hormone (GH) deficiency in adults. The central findings in both these syndromes are abdominal/visceral obesity and insulin resistance. Other features common to both conditions are premature atherosclerosis and increased mortality from cardiovascular diseases. These similarities indicate that undetectable and low levels of GH may be of importance in the metabolic aberrations observed in both these conditions. Recent investigations have found that abdominal/visceral distribution of adipose tissue is associated with endocrine disturbances including increased activity of the hypothalamic-pituitary-adrenal axis and a blunted secretion of GH and sex steroids. Theoretically, these endocrine perturbations can be a consequence of obesity, but the endocrine aberrations may have causal effects. We studied moderately obese, middle-aged men with a preponderance of abdominal body fat. As a group, they had slight to moderate metabolic changes known to be associated with abdominal/visceral obesity. Nine months of GH treatment reduced their total body fat and resulted in a specific and a marked decrease in both abdominal subcutaneous and visceral adipose tissue. Moreover, insulin sensitivity improved and serum concentrations of total cholesterol and triglyceride decreased. Diastolic blood pressure also decreased. The finding that GH replacement in men with abdominal obesity can diminish the negative metabolic consequences of visceral obesity suggests that low levels of this hormone are of importance for the metabolic aberrations associated with visceral/abdominal obesity.
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PMID:Growth hormone and the metabolic syndrome. 1044 70

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by a paucity of adipose (fat) tissue which is evident at birth and is accompanied by a severe resistance to insulin, leading to hyperinsulinaemia, hyperglycaemia and enlarged fatty liver. We have developed a mouse model that mimics these features of CGL: the syndrome occurs in transgenic mice expressing a truncated version of a nuclear protein known as nSREBP-1c (for sterol-regulatory-element-binding protein-1c) under the control of the adipose-specific aP2 enhancer. Adipose tissue from these mice was markedly deficient in messenger RNAs encoding several fat-specific proteins, including leptin, a fat-derived hormone that regulates food intake and energy metabolism. Here we show that insulin resistance in our lipodystrophic mice can be overcome by a continuous systemic infusion of low doses of recombinant leptin, an effect that is not mimicked by chronic food restriction. Our results support the idea that leptin modulates insulin sensitivity and glucose disposal independently of its effect on food intake, and that leptin deficiency accounts for the insulin resistance found in CGL.
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PMID:Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. 1048 7

Hepatic steatosis is common in non-insulin-dependent diabetes and can be associated with fibrosis and cirrhosis in a subset of individuals. Increased rates of fatty acid synthesis have been reported in livers from rodent models of diabetes and may contribute to the development of steatosis. Sterol regulatory element-binding proteins (SREBPs) are a family of regulated transcription factors that stimulate lipid synthesis in liver. In the current studies, we measured the content of SREBPs in livers from two mouse models of diabetes, obese ob/ob mice and transgenic aP2-SREBP-1c436 (aP2-SREBP-1c) mice that overexpress nuclear SREBP-1c only in adipose tissue. The aP2-SREBP-1c mice exhibit a syndrome that resembles congenital generalized lipodystrophy in humans. Both lines of mice develop hyperinsulinemia, hyperglycemia, and hepatic steatosis. Nuclear SREBP-1c protein levels were significantly elevated in livers from ob/ob and aP2-SREBP-1c mice compared with wild-type mice. Increased nuclear SREBP-1c protein was associated with elevated mRNA levels for known SREBP target genes involved in fatty acid biosynthesis, which led to significantly higher rates of hepatic fatty acid synthesis in vivo. These studies suggest that increased levels of nuclear SREBP-1c contribute to the elevated rates of hepatic fatty acid synthesis that leads to steatosis in diabetic mice.
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PMID:Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. 1051 88


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