scholarly journals Non-alcoholic steatohepatitis in patients with endocrine pathology. Review

2021 ◽  
pp. 82-93
Author(s):  
S. M. Tkach ◽  
Т. L. Cheverda
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary ◽  
Hormone Deficiency ◽  
Endocrine Disorders ◽  
Male Hypogonadism ◽  
Pathophysiological Mechanism ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Intestinal Dysbiosis ◽  
Obstructive Sleep

Non-alcoholic steatohepatitis (NASH) is a subtype of non-alcoholic fatty liver disease (NAFLD), which in the absence of treatment can progress to the development of cirrhosis and hepatocellular carcinoma, as well as to increased mortality associated with these diseases. The main risk factors for the development of NAFLD and NASH are the presence of insulin resistance and obesity. Quite often NAFLD and NASH are associated with so-called extrahepatic manifestations, such as obstructive sleep apnea, hypertension, dyslipidemia, intestinal dysbiosis, genetic predisposition, sedentary lifestyle and consumption of certain foods. However, NAFLD and NASH are also associated with some endocrine diseases and conditions, including type 2 diabetes, polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or excess, hypercortisolism, vitamin D or prolactin deficiency. In many of these diseases, the key pathophysiological mechanism is insulin resistance. This review considers the putative pathophysiological mechanisms that play an important pathogenetic role in the development of NASH in these endocrine disorders.Unfortunately, our understanding of the pathophysiology of NAFLD in various endocrinopathies is far from complete. In addition, the natural course of NAFLD due to endocrine disorders compared to the course and consequences of “primary” NAFLD is still poorly understood. Therefore, in the coming years, further research into the pathophysiology and clinical features of NASH will be important to better understand the relationship between different endocrinopathies and NAFLD, which will help improve the treatment of this pathology.

scholarly journals Dual-specificity phosphatase 3 deletion promotes obesity, non-alcoholic steatohepatitis and hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sophie Jacques ◽  
Arash Arjomand ◽  
Hélène Perée ◽  
Patrick Collins ◽  
Alice Mayer ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Damage ◽  
Chow Diet ◽  
Serum Triglycerides ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Dual Specificity ◽  
Dual Specificity Protein Phosphatase

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe and progressive non-alcoholic steatohepatitis (NASH) that can lead to hepatocellular carcinoma (HCC). Obesity and related metabolic syndrome are important risk factors for the development of NAFLD, NASH and HCC. DUSP3 is a small dual-specificity protein phosphatase with a poorly known physiological function. We investigated its role in metabolic syndrome manifestations and in HCC using a mouse knockout (KO) model. While aging, DUSP3-KO mice became obese, exhibited insulin resistance, NAFLD and associated liver damage. These phenotypes were exacerbated under high fat diet (HFD). In addition, DEN administration combined to HFD led to rapid HCC development in DUSP3-KO compared to wild type (WT) mice. DUSP3-KO mice had more serum triglycerides, cholesterol, AST and ALT compared to control WT mice under both regular chow diet (CD) and HFD. The level of fasting insulin was higher compared to WT mice, though, fasting glucose as well as glucose tolerance were normal. At the molecular level, HFD led to decreased expression of DUSP3 in WT mice. DUSP3 deletion was associated with increased and consistent phosphorylation of the insulin receptor (IR) and with higher activation of the downstream signaling pathway. In conclusion, our results support a new role for DUSP3 in obesity, insulin resistance, NAFLD and liver damage.

Polycystic Ovary Syndrome Is Associated With Obstructive Sleep Apnea and Daytime Sleepiness: Role of Insulin Resistance

2001 ◽  
Vol 56 (7) ◽  
pp. 418-419 ◽  
Author(s):  
Alexandros N. Vgontzas ◽  
Richard S. Legro ◽  
Edward O. Bixler ◽  
Allison Grayev ◽  
Anthony Kales ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Polycystic Ovary Syndrome ◽  
Daytime Sleepiness ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Obstructive Sleep

scholarly journals Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease

2009 ◽  
Vol 150 (48) ◽  
pp. 2173-2181 ◽  
Author(s):  
Krisztina Hagymási ◽  
Péter Reismann ◽  
Károly Rácz ◽  
Zsolt Tulassay
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Endocrine System ◽  
Hormone Deficiency ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing’s syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

scholarly journals The Polycystic Ovary Syndrome and the Metabolic Syndrome: A Possible Chronobiotic-Cytoprotective Adjuvant Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Eduardo Spinedi ◽  
Daniel P. Cardinali
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
White Adipose Tissue ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
The Metabolic Syndrome ◽  
Obstructive Sleep ◽  
The Impact

Polycystic ovary syndrome is a highly frequent reproductive-endocrine disorder affecting up to 8–10% of women worldwide at reproductive age. Although its etiology is not fully understood, evidence suggests that insulin resistance, with or without compensatory hyperinsulinemia, and hyperandrogenism are very common features of the polycystic ovary syndrome phenotype. Dysfunctional white adipose tissue has been identified as a major contributing factor for insulin resistance in polycystic ovary syndrome. Environmental (e.g., chronodisruption) and genetic/epigenetic factors may also play relevant roles in syndrome development. Overweight and/or obesity are very common in women with polycystic ovary syndrome, thus suggesting that some polycystic ovary syndrome and metabolic syndrome female phenotypes share common characteristics. Sleep disturbances have been reported to double in women with PCOS and obstructive sleep apnea is a common feature in polycystic ovary syndrome patients. Maturation of the luteinizing hormone-releasing hormone secretion pattern in girls in puberty is closely related to changes in the sleep-wake cycle and could have relevance in the pathogenesis of polycystic ovary syndrome. This review article focuses on two main issues in the polycystic ovary syndrome-metabolic syndrome phenotype development: (a) the impact of androgen excess on white adipose tissue function and (b) the possible efficacy of adjuvant melatonin therapy to improve the chronobiologic profile in polycystic ovary syndrome-metabolic syndrome individuals. Genetic variants in melatonin receptor have been linked to increased risk of developing polycystic ovary syndrome, to impairments in insulin secretion, and to increased fasting glucose levels. Melatonin therapy may protect against several metabolic syndrome comorbidities in polycystic ovary syndrome and could be applied from the initial phases of patients’ treatment.

Hypoxia aggravates non-alcoholic steatohepatitis in mice lacking hepatocellular PTEN

2009 ◽  
Vol 118 (6) ◽  
pp. 401-410 ◽  
Author(s):  
Anne-Christine Piguet ◽  
Deborah Stroka ◽  
Arthur Zimmermann ◽  
Jean-François Dufour
Keyword(s):  
Liver Disease ◽  
Insulin Sensitivity ◽  
Peroxisome Proliferator ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Lipogenic Genes ◽  
Alcoholic Steatohepatitis ◽  
Obstructive Sleep

The metabolic disorders that predispose patients to NASH (non-alcoholic steatohepatitis) include insulin resistance and obesity. Repeated hypoxic events, such as occur in obstructive sleep apnoea syndrome, have been designated as a risk factor in the progression of liver disease in such patients, but the mechanism is unclear, in particular the role of hypoxia. Therefore we studied the influence of hypoxia on the development and progression of steatohepatitis in an experimental mouse model. Mice with a hepatocellular-specific deficiency in the Pten (phosphatase and tensin homologue deleted on chromosome 10) gene, a tumour suppressor, were exposed to a 10% O2 (hypoxic) or 21% O2 (control) atmosphere for 7 days. Haematocrit, AST (aspartate aminotransferase), glucose, triacylglycerols (triglycerides) and insulin tolerance were measured in blood. Histological lesions were quantified. Expression of genes involved in lipogenesis and mitochondrial β-oxidation, as well as FOXO1 (forkhead box O1), hepcidin and CYP2E1 (cytochrome P450 2E1), were analysed by quantitative PCR. In the animals exposed to hypoxia, the haematocrit increased (60±3% compared with 50±2% in controls; P<0.01) and the ratio of liver weight/body weight increased (5.4±0.2% compared with 4.7±0.3% in the controls; P<0.01). Furthermore, in animals exposed to hypoxia, steatosis was more pronounced (P<0.01), and the NAS [NAFLD (non-alcoholic fatty liver disease) activity score] (8.3±2.4 compared with 2.3±10.7 in controls; P<0.01), serum AST, triacylglycerols and glucose were higher. Insulin sensitivity decreased in mice exposed to hypoxia relative to controls. The expression of the lipogenic genes SREBP-1c (sterol-regulatory-element-binding protein-1c), PPAR-γ (peroxisome-proliferator-activated receptor-γ), ACC1 (acetyl-CoA carboxylase 1) and ACC2 (acetyl-CoA carboxylase 2) increased significantly in mice exposed to hypoxia, whereas mitochondria β-oxidation genes [PPAR-α (peroxisome-proliferator-activated receptor-α) and CPT-1 (carnitine palmitoyltransferase-1)] decreased significantly. In conclusion, the findings of the present study demonstrate that hypoxia alone aggravates and accelerates the progression of NASH by up-regulating the expression of lipogenic genes, by down-regulating genes involved in lipid metabolism and by decreasing insulin sensitivity.

scholarly journals NAFLD: comorbidity and associated diseases

2020 ◽  
Vol 1 (10) ◽  
pp. 57-65 ◽  
Author(s):  
M. A. Livzan ◽  
O. V. Gaus ◽  
N. A. Nikolaev ◽  
T. S. Krolevetz
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Fatty Liver Disease ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Alcoholic Fatty Liver ◽  
Pathological Conditions ◽  
Obstructive Sleep ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) went beyond the competence of a gastroenterologist and acquired the character of a multidisciplinary problem. NAFLD requires the attention of many professionals. A characteristic feature of NAFLD is the variety of concomitant diseases and pathological conditions with common pathophysiological mechanisms. This review summarizes and presents the data available in the modern literature on the association of NAFLD with cardiovascular diseases, type 2 diabetes mellitus, hypothyroidism, polycystic ovary syndrome, chronic kidney disease, colorectal cancer, obstructive sleep apnea, osteoporosis, psoriasis.

scholarly journals INSULIN RESISTANCE INCREASES OBSTRUCTIVE SLEEP APNEA RISK IN NON-OBESE WOMEN WITH POLYCYSTIC OVARY SYNDROME

2020 ◽  
Vol 114 (3) ◽  
pp. e400
Author(s):  
Xiaojie P. Zhou ◽  
Eleni Greenwood Jaswa ◽  
Nikolaus J. Lenhart ◽  
Jamie Corley ◽  
Marcelle I. Cedars ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Obstructive Sleep

scholarly journals Soybean oil attenuates the onset of non-alcoholic steatohepatitis and insulin resistance

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Victor Sanchez ◽  
Anna Janina Engstler ◽  
Annette Brandt ◽  
Cheng Jun Jin ◽  
Dragana Rajcic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Soybean Oil ◽  
Mrna Expression ◽  
Liver Tissue ◽  
Metabolic Diseases ◽  
Insulin Receptors ◽  
Signaling Cascade ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Tlr4 Mrna

AbstractBackground and Aims:General overnutrition, and a diet rich in fat and sugar are among the key risk factors for the development of metabolic diseases including diabetes type 2 and non-alcoholic fatty liver diseases (NAFLD). While being among the most commonly consumed oils world-wide, the effects of soybean oil on the development of metabolic diseases are yet not understood. Indeed, existing data is in part contradictory. Based on this background, the aim of the present study was to investigate the effects of soybean oil consumption on the development of non-alcoholic steatohepatitis (NASH), the more progressed stage of NAFLD, and insulin resistance.Methods:Female C57BL/6J mice were fed either a liquid standard control diet (C) or a liquid fat-, fructose- and cholesterol-rich diet (FFC, 25E% butterfat, 50% (wt/wt) fructose, 0.155% (wt/wt) cholesterol) or a FFC supplemented with soybean oil (FFC + S, 21E% butterfat + 4E% soy oil), with FFC and FFC + S-fed groups being pair fed for 13 weeks to induce steatohepatitis. After 7 and 12 weeks of feeding, a glucose tolerance test was performed. Indicators of liver damage, inflammation, intestinal barrier function and markers of insulin signaling cascade were measured in intestinal, liver and muscle tissue.Results:As expected FFC-fed mice developed early signs of NASH and insulin resistance. Despite similar caloric intake and body weight gain, development of NASH and insulin resistance were significantly attenuated in FFC + S-fed mice when compared to FFC-fed animals. Indeed, signs of hepatic inflammation e.g. number of inflammatory foci and neutrophils as well as activity of transaminase in plasma were almost at the level of control in FFC + S-fed mice. Prevalence of macrovesicular steatosis being the predominant type of fat accumulation found in FFC-fed animals was also markedly lower in FFC + S-fed mice. Furthermore, while in muscle and liver tissue of FFC-fed mice insulin receptors mRNA expression was significantly different from C-fed animals, insulin receptors expression in FFC + S-fed mice was almost at the level of controls. The protective effects of soybean oil supplementation on the development of metabolic alterations were associated with a protection against the induction of TLR4 mRNA expression and dependent signaling molecules in liver tissue.Conclusion:Taking together, our results indicate that supplementation with soybean oil may attenuate the development of diet-induced NASH and insulin resistance in mice and that this may be related to alteration of TLR4-dependent signaling cascade in liver tissue. (Funded in parts by UFOP e.V.)

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