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)

Abdominal obesity is often associated with a constellation of comorbidities that include central adiposity, insulin resistance, dyslipidemia, and hypertension. Clinical evaluations should include a measurement of waist circumference, which is a good marker of abdominal obesity. Abdominal obesity is closely associated with an elevated outflow of free fatty acids from the visceral fat compartment and dysregulation of adipokine expression, accompanied by increased inflammation. The most serious consequences of abdominal obesity are coronary heart disease and stroke. It is also associated, however, with polycystic ovary syndrome and hepatic steatosis. Weight reduction and increased physical activity should be recommended to patients with a high waist circumference. Patients with abdominal obesity and other classic risk factors are at high cardiovascular risk and require strict monitoring of their blood pressure, LDL-c, and blood glucose. New pharmacological strategies might help manage both abdominal obesity and its metabolic consequences.
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PMID:[Abdominal obesity: a health threat]. 1841 15

Nonalcoholic fatty liver disease (NAFLD) is a condition pathogenically linked to metabolic syndrome (MS) by insulin resistance (IR), and characterized by hepatic steatosis in the absence of significant alcohol use, hepatotoxicity, and/or other known liver diseases.The principles of NAFLD therapy target IR: the key point of MS. As the renin-angiotensin system (RAS) plays a central role in IR, and subsequently in NAFLD and nonalcoholic steatohepatitis (NASH), an attempt to block the deleterious effects of RAS overexpression seems a logical target. While many potential therapies tested in NASH target only the consequences of this condition, or try to "get rid" of excessive fat, angiotensin receptor blockers (ARBs) could act as an elegant tool for adequate correction of the various imbalances that act in harmony in NASH/NAFLD. Indeed, by inhibiting RAS we can improve the intracellular insulin signaling pathway, better control adipose tissue proliferation and adipokine production, and produce more balanced local and systemic levels of various cytokines. At the same time, by controlling the local RAS in the liver we might be able to prevent at least fibrosis and also slow down the vicious cycle that links steatosis to necroinflammation. By targeting the pancreatic effects of angiotensin we should be able to preserve an adequate insulin secretion and acquire a better metabolic balance.In our opinion there are two major advantages of ARBs that make them a possible therapeutic option for treating NASH and MS: their specific antihypertensive effect, and their impact on liver fibrosis. In light of this, and based on the current evidence (including existent human studies), we can speculate that some ARBs like telmisartan, candesartan, and losartan can be beneficial in treating NASH/NAFLD and its consequences, and further larger controlled clinical trials will bring consistent data into this field.
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PMID:Angiotensin receptor blockers in the treatment of NASH/NAFLD: could they be a first-class option? 1897 77

Adipose tissue is critical in energy homeostasis. Adipose tissue 'buffers' the lipids and energy rich compounds which are pumped into the blood stream soon after meals. It senses, signals other organs like liver and brain about the energy reserves via adipokines. Adiponectin, the most abundant adipokine has insulin sensitizing, anti-inflammatory antiatherogenic and antisteatotic effects. Adipose tissue dysfunction is accompanied by abnormal lipid distribution and storage which contributes to diseases like diabetes, nonalcoholic fatty liver disease and atherosclerosis. Obesity and lipodystrophy are associated with dysfunctional adipocytes. Pre-adipocytes are easy to isolate and culture. A personalized depot specific liposuction to remove the inactive adipocytes followed by adipocyte repopulation could be useful in the treatment of these diseases.
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PMID:Adipose tissue transplantation may be a potential treatment for diabetes, atherosclerosis and nonalcoholic steatohepatitis. 1904 21

Subcutaneous and visceral adipose compartments act, not only as fatty acid depots, but also as active endocrine organs that undergo hyperplastic changes and significantly enhance their function in obesity. Akipokines and other proteins secreted by both adipocytes and stromal cells play a central role in peripheral insulin resistance and the metabolic syndrome (MS). Minor alleles of the adipokine genes substantially contribute to MS. The most important consequence of MS is low-level systemic inflammation supported by adipose-specific synthesis of proinflammatory soluble molecules. Proinflammatory signals are secreted into the bloodstream and spread to peripheral tissues that contain their receptors. The signals provided by adipose tissue stimulate the development of secondary complications of MS, including cardiovascular disorders (CVDs) and nonalcoholic fatty liver disease. The review describes the physiological effects of adiponectin, leptin, resistin, visfatin, and apelin and the influence of the minor alleles of the adipokine genes on the development of the secondary complications of MS.
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PMID:[Adipokine genetics: unbalanced protein secretion by human adipose tissue as a cause of the metabolic syndrome]. 1906 31

Alcoholic liver disease still represents an important cause for death and disability in most well-developed countries and is becoming a leading cause of disease in developing countries. It is now increasingly clear that, besides the formation of acetaldehyde, alcohol effects on the liver include oxidative stress, disturbances in methionine metabolism, endoplasmic reticulum stress, inflammatory/immune responses and adipokine imbalances. This article will discuss the most recent findings on the mechanisms by which alcohol abuse causes hepatic steatosis and steatohepatitis, and now it contributes to the progression of fibrosis. Although still incomplete, these data shed new light on the multifactorial pathogenesis of alcoholic liver disease and open new possibilities in the understanding of how gender and genetic factors can influence disease progression.
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PMID:New concepts in the pathogenesis of alcoholic liver disease. 1909 Jul 36

We aimed at determining which circulating forms of the adipokine adiponectin that increases lipid oxidation in liver and skeletal muscle are related to ectopic fat in these depots in humans. Plasma total-, high-molecular weight (HMW)-, middle-molecular weight (MMW)-, and low-molecular weight (LMW) adiponectin were quantified by an enzyme-linked immunosorbent assay. Their relationships with liver- and intramyocellular fat, measured using (1)H magnetic resonance spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat, adjusted for gender, age, and total body fat, was associated only with HMW adiponectin (r = -0.35, P = 0.012), but not with total-, MMW-, or LMW adiponectin. In addition, subjects with fatty liver (liver fat > or =5.56%, n = 15) had significantly lower HMW- (P = 0.04), but not total-, MMW-, or LMW adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular fat correlated only with HMW (r = -0.32, P = 0.039), but not with the other circulating forms of adiponectin. These data indicate that, among circulating forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly representing the form of adiponectin regulating lipid oxidation in liver and skeletal muscle.
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PMID:Adiponectin oligomers and ectopic fat in liver and skeletal muscle in humans. 1916 22

Epidemiological data indicate a strong risk for development of insulin resistance (IR), and, ultimately, overt diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection. Steatosis, or fatty liver, is closely linked with IR in persons without HCV, such as those with metabolic syndrome, primarily due to increased visceral fat leading to altered adipokine production and increased free fatty acid (FFA) release. Moreover, there is evidence that liver fat can have an impact on the development of hepatic IR independently of changes in adipose tissue. Multiple mechanisms can account for the development of IR in patients with chronic HCV. In particular, there is evidence for a triangular interaction between steatosis, inflammatory processes and IR. In patients infected by the genotype 1 virus, steatosis is strongly related to IR, leading to a metabolic steatosis, while, in genotype 3 patients, steatosis is related to viral load in the context of a viral steatosis. Chronic inflammatory processes in the liver may be mediated by persistently activated macrophages and other immune cells, with concomitant overproduction of pro-inflammatory cytokines such as tumour necrosis factor-alpha. Activation of inflammatory pathways, together with increased levels of FFAs, can disrupt hepatocyte intracellular pathways and inhibit insulin signalling, leading to IR. Molecular studies have also shown that the HCV core protein can directly inhibit the insulin signalling pathway and increase reactive oxygen species production, both of which can further exacerbate IR. The available data provide an understanding of chronic HCV whereby chronic inflammatory processes, steatosis and IR contribute to each other, leading to an increased risk of DM, and its associated poor outcomes, in persons with chronic HCV.
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PMID:Hepatitis C, insulin resistance and diabetes: clinical and pathogenic data. 1918 69

Omega-3-polyunsaturated fatty acids (omega-3-PUFAs) have well-documented protective effects that are attributed not only to eicosanoid inhibition but also to the formation of novel biologically active lipid mediators (i.e., resolvins and protectins). In this study, we examined their effects on ob/ob mice, an obesity model of insulin resistance and fatty liver disease. Dietary intake of omega-3-PUFAs had insulin-sensitizing actions in adipose tissue and liver and improved insulin tolerance in obese mice. Genes involved in insulin sensitivity (PPARgamma), glucose transport (GLUT-2/GLUT-4), and insulin receptor signaling (IRS-1/IRS-2) were up-regulated by omega-3-PUFAs. Moreover, omega-3-PUFAs increased adiponectin, an anti-inflammatory and insulin-sensitizing adipokine, and induced AMPK phosphorylation, a fuel-sensing enzyme and a gatekeeper of the energy balance. Concomitantly, hepatic steatosis was alleviated by omega-3-PUFAs. A lipidomic analysis with liquid chromatography/mass spectrometry/mass spectrometry revealed that omega-3-PUFAs inhibited the formation of omega-6-PUFA-derived eicosanoids, while triggering the formation of omega-3-PUFA-derived resolvins and protectins. Moreover, representative members of these lipid mediators, namely resolvin E1 and protectin D1, mimicked the insulin-sensitizing and antisteatotic effects of omega-3-PUFAs and induced adiponectin expression to a similar extent that of rosiglitazone, a member of the thiazolidinedione family of antidiabetic drugs. Taken together, these findings uncover beneficial actions of omega-3-PUFAs and their bioactive lipid autacoids in preventing obesity-induced insulin resistance and hepatic steatosis.
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PMID:Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. 1921 25

Increases in adiposity trigger metabolic and inflammatory changes that interfere with insulin action in peripheral tissues, culminating in beta cell failure and overt diabetes. We found that the cAMP Response Element Binding protein (CREB) is activated in adipose cells under obese conditions, where it promotes insulin resistance by triggering expression of the transcriptional repressor ATF3 and thereby downregulating expression of the adipokine hormone adiponectin as well as the insulin-sensitive glucose transporter 4 (GLUT4). Transgenic mice expressing a dominant-negative CREB transgene in adipocytes displayed increased whole-body insulin sensitivity in the contexts of diet-induced and genetic obesity, and they were protected from the development of hepatic steatosis and adipose tissue inflammation. These results indicate that adipocyte CREB provides an early signal in the progression to type 2 diabetes.
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PMID:Adipocyte CREB promotes insulin resistance in obesity. 1925 72

The incidence of obesity has increased dramatically during recent decades. Obesity will cause a decline in life expectancy for the first time in recent history due to numerous co-morbid disorders. Adipocyte and adipose tissue dysfunction belong to the primary defects in obesity and may link obesity to several health problems including increased risk of insulin resistance, type 2 diabetes, fatty liver disease, hypertension, dyslipidemia, atherosclerosis, dementia, airway disease and some cancers. However, not all obese individuals develop obesity related metabolic or cardiovascular disorders potentially due to a preserved normal adipose tissue architecture and function. The majority of patients with obesity have an impaired adipose tissue function caused by the interaction of genetic and environmental factors which lead to adipocyte hypertrophy, hypoxia, a variety of stresses and inflammatory processes within adipose tissue. Ectopic fat accumulation including visceral obesity may be considered as a consequence of adipose tissue dysfunction, which is further characterized by changes in the cellular composition, increased lipid storage and impaired insulin sensitivity in adipocytes, and secretion of a proinflammatory, atherogenic, and diabetogenic adipokine pattern. This review focuses on the discussion of mechanisms causing or maintaining impaired adipose tissue function in obesity and potentially linking obesity to its associated disorders. A model is proposed how different pathogenic factors and mechanisms may cause dysfunction of adipose tissue.
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PMID:Adipose tissue dysfunction in obesity. 1935 89


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