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Query: UMLS:C0015695 (fatty liver)
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The insulin resistance syndrome (syndrome X, metabolic syndrome) has become the major health problem of our times. Associated obesity, dyslipidemia, atherosclerosis, hypertension, and type 2 diabetes conspire to shorten life spans, while hyperandrogenism with polycystic ovarian syndrome affect the quality of life and fertility of increasing numbers of women. Whereas a growing number of single genetic diseases affecting satiety or energy metabolism have been found to produce the clinical phenotype, strong familial occurrences, especially in racially prone groups such as those from the Indian subcontinent, or individuals of African, Hispanic, and American Indian descents, together with emerging genetic findings, are revealing the polygenetic nature of the syndrome. However, the strong lifestyle factors of excessive carbohydrate and fat consumption and lack of exercise are important keys to the phenotypic expression of the syndrome. The natural history includes small for gestational age birth weight, excessive weight gains during childhood, premature pubarche, an allergic diathesis, acanthosis nigricans, striae compounded by gynecomastia, hypertriglyceridemia, hepatic steatosis, premature atherosclerosis, hypertension, polycystic ovarian syndrome, and focal glomerulonephritis appearing increasingly through adolescence into adulthood. Type 2 diabetes, which develops because of an inherent and/or an acquired failure of an insulin compensatory response, is increasingly seen from early puberty onward, as is atheromatous disease leading to coronary heart disease and stroke. A predisposition to certain cancers and Alzheimer's disease is also now recognized. The looming tragedy from growing numbers of individuals affected by obesity/insulin resistance syndrome requires urgent public health approaches directed at their early identification and intervention during childhood. Such measures include educating the public on the topic, limiting the consumption of sucrose-containing drinks and foods with high carbohydrate and fat contents, and promoting exercise programs in our nation's homes and schools.
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PMID:Insulin resistance syndrome in children. 1518 Oct 20

The effect of significant weight loss on nonalcoholic fatty liver disease remains unclear. In this case series of 36 selected obese patients, we examined the effect of weight loss on nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. These 36 patients (11 males, 25 females) had paired liver biopsies, the first at the time of laparoscopic adjustable gastric band placement and the second after weight loss. Second biopsies were obtained from two groups: those requiring a subsequent laparoscopic procedure (n = 19) and those with index biopsy score of 2 or greater for zone 3-centric hepatic fibrosis (n = 17). All biopsies were scored, blinded to the patient's identity and clinical condition, for individual histological features and for NASH stage and grade. Initial biopsies demonstrated NASH in 23 patients and steatosis in 12 patients. Repeat biopsies were taken at 25.6 +/- 10 months (range, 9-51 months) after band placement. Mean weight loss was 34.0 +/- 17 kg, and percentage of excess weight loss was 52 +/- 17%. There were major improvements in lobular steatosis, necroinflammatory changes, and fibrosis at the second biopsy (P <.001 for all). Portal abnormalities remained unchanged. Only four of the repeat biopsies fulfilled the criteria for NASH. There were 18 patients with an initial fibrosis score of 2 or more compared with 3 patients at follow-up (P <.001). Those with the metabolic syndrome (n = 23) had more extensive changes before surgery and greater improvement with weight loss. In conclusion, weight loss after surgery provides major improvement or resolution of obesity and metabolic syndrome-associated abnormal liver histological features in severely obese subjects.
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PMID:Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. 1518 6

Metabolic syndrome is a pathophysiological state in which risks for atherosclerosis are clustered. Etiology of metabolic syndrome is multi-factorial. Excess energy intake causes imbalance of energy transcription factors such as PPARs and SREBP-1c, which are deeply involved in lipid and carbohydrate metabolism, leading to insulin resistance and dyslipidemia. Especially hepatic SREBP-1c could be involved in production of remnant lipoproteins, fatty liver, and hepatic insulin resistance. Meanwhile, currently, therapeutic trend is activation of energy expenditure, in which PPAR alpha, delta, and AMP kinase are current targets of treatment. Proinflammatory agents should also be involved and adipocytokines could play an important role in peripheral insulin resistance.
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PMID:[Pathophysiology of metabolic syndrome]. 1520 38

Insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflammatory cytokines have been suggested to contribute to the development of these disorders, the molecular mechanism is poorly understood. Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c. Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia. In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity. Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.
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PMID:Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse. 1524 Aug 80

Nonalcoholic steatohepatitis (NASH) represents an advanced stage of fatty liver disease developed in the absence of alcohol abuse. Its increasing prevalence in western countries, the diagnostic difficulties by noninvasive tests, and the possibility of progression to advanced fibrosis and even cirrhosis make NASH a challenge for hepatologists. NASH is frequently associated with type 2 diabetes and the metabolic syndrome, and several genetic and acquired factors are involved in its pathogenesis. Insulin resistance plays a central role in the development of a steatotic liver, which becomes vulnerable to additional injuries. Several cyclic mechanisms leading to self-enhancement of insulin resistance and hepatic accumulation of fat have been recently identified. Excess intracellular fatty acids, oxidant stress, tumor necrosis factor-alpha, and mitochondrial dysfunction are causes of hepatocellular injury, thereby leading to disease progression and to the establishment of NASH. Intestinal bacterial overgrowth also plays a role, by increasing production of endogenous ethanol and proinflammatory cytokines. Therapeutic strategies aimed at modulating insulin resistance, normalizing lipoprotein metabolism, and downregulating inflammatory mediators with probiotics have promising potential.
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PMID:Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. 1527 42

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can lead to hepatic fibrosis and cirrhosis. Portal fibrosis in the absence of NASH, called isolated portal fibrosis (IPF), has received less attention and has not been classified as a spectrum of NAFLD. The aims of this study were to determine the prevalence of IPF in subjects undergoing gastric bypass surgery, to identify biochemical variables associated with IPF, and to assess the metabolic syndrome as defined by the AdultTreatment Panel III criteria. We analyzed liver biopsies from 195 morbidly obese subjects after excluding all other causes of liver disease. The prevalence of fatty liver (FL) only, IPF, and NASH was 30.3%, 33.3%, and 36.4%, respectively. Several biochemical parameters significantly trended across the 3 groups, with IPF falling between FL and NASH. Hyperglycemia was the only metabolic parameter associated with NASH (OR, 5.4; 95% CI, 2.4-12; P < .0001) and IPF (OR, 2.8; 95% CI, 1.2-6.5; P = .01). Subjects with diabetes had the greatest risk for NASH (OR, 8; 95% CI, 3.3-19.7; P < .0001) and IPF (OR, 4.3; 95% CI, 1.6-11.6; P = .003). The metabolic syndrome was identified in 78.5% of subjects, and a significant trend for the number of metabolic criteria was observed across the spectrum of FL, IPF, and NASH. In conclusion, a significant subset of morbidly obese individuals has portal fibrosis in the absence of NASH that is associated with glycemic dysregulation. Therefore, IPF should be considered a spectrum of NAFLD that may prelude NASH in morbid obesity.
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PMID:Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease. 1536 53

Metabolic syndrome also can be named insulin resistance syndrome. The main clinical manifestations include metabolic disorders of glucose and lipid and some diseases caused by the metabolic disorder, such as impaired glucose tolerance or diabetes, obesity, hyperlipemia, fatty liver, hypertension, coronary heart disease, microalbuminuria, etc. According to the theory of zang-fu organs (viscera) in traditional Chinese medicine, these diseases all result from the deficiency of spleen-qi. They are characterized by deficiency in the Ben (root) and excess in the Biao (branch). The Ben (root) is the failure of the spleen in transportation, and the Biao (branch) is stagnation of qi, blood, phlegm, fire, dampness and food. In the prevention and treatment of metabolic syndrome, it is advocated that the intervention of medicine should be used as early as possible, so as to slow down the occurrence and development of insulin resistance, and that emphasis should be transferred from decreasing blood glucose alone to comprehensive prevention of risk factors, especially to the prevention of cardiovascular events. The effect of traditional Chinese herbs is not as good as the western drugs in decreasing the blood pressure and glucose. However, the traditional Chinese herbs have distinctive superiority in ameliorating the insulin resistance, protecting the injury of vascular endothelial cells, regulating the metabolism of lipid, inhibiting the hypercoagulability, and treating the inflammation. Moreover, they are relatively safe. Therefore, the integration of the traditional Chinese medicine and western medicine is worth further research.
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PMID:[Prevention and treatment of metabolic syndrome with integrated traditional Chinese and western medicine]. 1538 69

The metabolic syndrome is one of the most common disease of our era that may cause numerous complications. There are some studies showing the need to take attention to the hepatic manifestation of the metabolic syndrome besides its already well-known consequences. In most of the cases there are histopathological evidences for the presence of fatty liver and mainly non alcoholic steatohepatitis. These conditions can lead to hepatic cirrhosis, hepatic failure or even to hepatocellular carcinoma. The risk of these consequences is the greater the more severe the metabolic syndrome is and the more components of it are included. All these emphasise the importance of examining the hepathological status of the patients suffering from the metabolic syndrome.
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PMID:[Is non alcoholic steatohepatitis (NASH) part of the metabolic syndrome?]. 1545 20

Chronic aethylism has always been a major social as well as health problem. It may lead, at least in some patients, to steatohepatitis (ASH) which is known to progress to cirrhosis more rapidly. Because of the fact that the prevalence of obesity in association with the metabolic syndrome (insulin resistance) is strikingly increasing in the Western world, we will more and more often be faced with a second form of steatohepatitis, the so called non-alcoholic steatohepatitis (NASH). Clinical differentiation between these two entities may often be difficult. The use of the CAGE-questions as well as interviewing family members can help to indentify hidden alcohol abuse. Clinically, the presence of both diseases can only be speculated. To get the diagnosis, liver biopsy must be performed to show the typical histologic feature of fatty liver with hepatocyte necrosis as well as infiltration of polymorphcellular leukocytes. Histology cannot differentiate between ASH and NASH. Therefore, similar pathogenetic mechanisms are supposed. However, therapeutic approaches are different. Treatment of choice in ASH is alcohol abstinence, that of NASH the reduction of insulin resistance, primarily by weight loss.
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PMID:[Alcoholic and non-alcoholic steatohepatitis]. 1545 67

The prevalence of the metabolic syndrome is increasing owing to lifestyle changes leading to obesity. This syndrome is a complex association of several interrelated abnormalities that increase the risk for cardiovascular disease and progression to diabetes mellitus (DM). Insulin resistance is the key factor for the clustering of risk factors characterizing the metabolic syndrome. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III defined the criteria for the diagnosis of the metabolic syndrome and established the basic principles for its management. According to these guidelines, treatment involves the improvement of the underlying insulin resistance through lifestyle modification (eg, weight reduction and increased physical activity) and possibly by drugs. The coexistent risk factors (mainly dyslipidemia and hypertension) should also be addressed. Since the main goal of lipid-lowering treatment is to achieve the NCEP low-density lipoprotein cholesterol (LDL-C) target, statins are a good option. However, fibrates (as monotherapy or in combination with statins) are useful for the treatment of the metabolic syndrome that is commonly associated with hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) levels. The blood pressure target is < 140/90 mm Hg. The effect on carbohydrate homeostasis should possibly be taken into account in selecting an antihypertensive drug. Patients with the metabolic syndrome commonly have other less well-defined metabolic abnormalities (eg, hyperuricemia and raised C-reactive protein levels) that may also be associated with an increased cardiovascular risk. It seems appropriate to manage these abnormalities. Drugs that beneficially affect carbohydrate metabolism and delay or even prevent the onset of DM (eg, thiazolidinediones or acarbose) could be useful in patients with the metabolic syndrome. Furthermore, among the more speculative benefits of treatment are improved liver function in nonalcoholic fatty liver disease and a reduction in the risk of acute gout.
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PMID:Prevention and treatment of the metabolic syndrome. 1554 46


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