‘Endocrine NAFLD’ a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis

Lonardo, Amedeo; Carani, Cesare; Carulli, Nicola; Loria, Paola

doi:10.1016/j.jhep.2006.03.005

Cited by 129 publications

(115 citation statements)

References 186 publications

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“…In this respect, hepatic fat accumulation has been demonstrated in patients with Cushing's syndrome [134,135], and GC levels have been found to be dramatically increased in various animal models of obesity, dyslipidemia, and hepatic steatosis, such as the db/db, ob/ob, and KKA(y) mouse [136,137]. Indeed, treatment of rats with GCs leads to increased triglyceride synthesis, decreased fatty acid oxidation, and to the subsequent accumulation of lipids in the liver [138].…”

Section: Gcs and Hepatic Lipid Metabolismmentioning

confidence: 99%

Glucocorticoids, metabolism and metabolic diseases

Vegiopoulos

Herzig

2007

Molecular and Cellular Endocrinology

448

370

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Since the discovery of the beneficial effects of adrenocortical extracts for treating adrenal insufficiency more than 80 years ago, glucocorticoids (GC) and their cognate, intracellular receptor, the glucocorticoid receptor (GR) have been characterized as critical components of the delicate hormonal control system that determines energy homeostasis in mammals.Whereas physiological levels of GCs are required for proper metabolic control, excessive GC action has been tied to a variety of pandemic metabolic diseases, such as type II diabetes and obesity. Highlighted by its importance for human health, the investigation of molecular mechanisms of GC/GR action has become a major focus in biomedical research. In particular, the understanding of tissue-specific functions of the GC-GR pathway has been proven to be of substantial value for the identification of novel therapeutic options in the treatment of severe metabolic disorders. Therefore, this review focuses on the role of the GC-GR axis for metabolic homeostasis and dysregulation, emphasizing tissue-specific functions of GCs in the control of energy metabolism.

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Section: Gcs and Hepatic Lipid Metabolismmentioning

confidence: 99%

Glucocorticoids, metabolism and metabolic diseases

Vegiopoulos

Herzig

2007

Molecular and Cellular Endocrinology

448

370

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“…14 Similar differences in the prevalence of NAFLD and elevated ALT by ethnic group have been consistently documented in adults. [15][16][17][18] Intrauterine factors are important determinants of components of the metabolic syndrome, 19 and there is evidence that intrauterine factors are also important in liver development and function. According to the fetal programming hypothesis, fetal undernutrition in mid and late gestation results in maintaining the brain at the expense of the growth of the trunk, including the liver, 20-22 which may result in permanent alterations to liver function.…”

Section: Introductionmentioning

confidence: 99%

“…23 In a cohort of older British women, inverse associations between birthweight and levels of ALT, gammaglutamyltransferase (GGT) and alkaline phosphatase (ALP) were found even when controlling for potential confounders. 24 The aims of this study were to estimate the prevalence of ALT elevation in a general adolescent population; to examine whether a range of early life characteristics are associated with elevated ALT in adolescence; and to determine the magnitude and strength of these associations in adolescent participants (defined as age [12][13][14][15][16][17][18][19] …”

Section: Introductionmentioning

confidence: 99%

Prevalence of Elevated Alanine Aminotransferase Among US Adolescents and Associated Factors: NHANES 1999–2004

2007

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Background & aims-Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver disease in children and adolescents. The majority of studies of NAFLD in children have been in select populations of the clinically obese. Study aims were to estimate the prevalence of elevated alanineaminotransferase (ALT, as a marker of NAFLD) in a general contemporary adolescent population and to identify leading risk factors for ALT elevation (> 30 U/L). Conclusions-ALT is associated with waist circumference and insulin resistance even in a young population. These characteristics could be utilized to identify adolescents who may benefit from screening for NAFLD, offering an opportunity to prevent disease progression at an early age. Methods-We

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“…2 Interestingly, in unselected consecutive subjects referred by General Practitioners for the evaluation of a "bright" liver at ultrasound scanning and enrolled in the POLISTENA study, NAFLD also displays a gender-dimorphic pattern. Indeed, in the majority of studies published in the 2000-2005 literature, 3 it occurs more frequently in the male gender. 4 It is amazing that our results, which were collected in a series recruited in the GPs offices in Modena, 4 closely mirror those by Marchesini et al in Bologna and Turin, 5 in the context of metabolic and liver Units (Table 1).…”

mentioning

confidence: 99%

“…In our opinion, gender differences in steatosis might also mirror derangements of other endocrine hormones, notably insulin, growth and thyroid hormones and cytokines, particularly adiponectin and leptin in NAFLD patients. 3 As far as GGT is concerned, this enzyme might be a simple and reliable marker of insulin resistance both in obesity 9 and in patients with NAFLD or HCV-related steatosis. 10 It is well known that both alanine aminotransferase and, more closely, GGT predict the onset of type 2 diabetes in the general population.…”

mentioning

confidence: 99%

Gender, fatty liver and GGT

et al. 2006

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We would like to comment on the paper by Cammà et al., 1 who report on gender differences in hepatitis C virus (HCV)-related steatosis and on elevated gamma-glutamyl transferase (GGT) values as a predictor of poor response to antiviral treatment. 1 In our opinion, these data could be better understood taking into account that HCV genotype 1-related steatosis closely resembles non-alcoholic fatty liver disease (NAFLD). 2 Interestingly, in unselected consecutive subjects referred by General Practitioners for the evaluation of a "bright" liver at ultrasound scanning and enrolled in the POLISTENA study, NAFLD also displays a gender-dimorphic pattern. Indeed, in the majority of studies published in the 2000-2005 literature, 3 it occurs more frequently in the male gender. 4 It is amazing that our results, which were collected in a series recruited in the GPs offices in Modena, 4 closely mirror those by Marchesini et al. in Bologna and Turin,5 in the context of metabolic and liver Units (Table 1). These data indicate that male patients with NAFLD are approximately 10 years younger than women with this condition. Women, though, tend to have a higher prevalence of metabolic derangements evaluated according to Adult Treatment Panel III.It is tempting to speculate that the circulating levels of estrogens within a physiological range might be responsible for a "protective" effect on the development of steatosis (due to both NAFLD and, presumably, HCV genotype 1). This would imply that women in the fertile age are relatively spared from the development of steatosis and that this protection vanes after menopause similar to what happens for cardiovascular disease. These findings are also supported by the association of NAFLD with the use of the anti-estrogen tamoxifen, 6 by the better profile of liver function enzymes in post-menopausal women taking hormone replacement therapy, 7 and finally by the finding that estradiol improves insulin sensitivity, 8 possibly preventing or reducing fat accumulation. In our opinion, gender differences in steatosis might also mirror derangements of other endocrine hormones, notably insulin, growth and thyroid hormones and cytokines, particularly adiponectin and leptin in NAFLD patients. 3 As far as GGT is concerned, this enzyme might be a simple and reliable marker of insulin resistance both in obesity 9 and in patients with NAFLD or HCV-related steatosis. 10 It is well known that both alanine aminotransferase and, more closely, GGT predict the onset of type 2 diabetes in the general population. 10 These observations fit with the finding that insulin resistance impairs the response to antiviral treatment, 1 and lead us to conclude that elevated GGT, insulin resistance, and impaired response to antiviral treatment form an ominous triangle in the context of chronic HCV infection.In conclusion, advances in the pathogenesis of NAFLD made over the past few years might give new clues to the understanding and, possibly, the treatment of HCV-associated steatosis. 2

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‘Endocrine NAFLD’ a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis

Cited by 129 publications

References 186 publications

Glucocorticoids, metabolism and metabolic diseases

Glucocorticoids, metabolism and metabolic diseases

Prevalence of Elevated Alanine Aminotransferase Among US Adolescents and Associated Factors: NHANES 1999–2004

Gender, fatty liver and GGT

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