Leptin, free leptin index, insulin resistance and liver fibrosis in children with non-alcoholic fatty liver disease

Nobili, Valério; Manco, Melania; Ciampalini, Paolo; Diciommo, Vincenzo; Vito, Rita De; Piemonte, Fiorella; Comparcola, Donatella; Guidi, Roberto; Marcellini, Matilde

doi:10.1530/eje.1.02288

Cited by 89 publications

(60 citation statements)

References 52 publications

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“…Investigations focusing on the relationship between leptin and steatosis revealed that serum leptin levels in patients with NASH were positively correlated with hepatic steatosis, fibrosis, and inflammation, as well as with serum lipids, glucose, insulin, c-peptide, and alanine aminotransferase (ALT) levels (Chitturi et al, 2002;Nobili et al, 2006). Studies in rodent models revealed that leptin prevented lipotoxicity by attenuating triglyceride accumulation in the liver, and activation of defective leptin signaling in fa/fa rats was found to massively reduce hepatic triglyceride contents (Chitturi et al, 2002;Leclercq et al, 2002;Unger, 2002).…”

Section: Endocrine Mediators and Signaling Network In Hepatic Steatomentioning

confidence: 99%

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

Anderson

Borlak²

2008

Pharmacological Reviews

342

255

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Section: Endocrine Mediators and Signaling Network In Hepatic Steatomentioning

confidence: 99%

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

Anderson

Borlak²

2008

Pharmacological Reviews

342

255

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“…Specimens were cut into 5 mol/L sections and stained using the Perls' Prussian blue technique for the detection of iron-positive cells, such as activated macrophages. 16 Five sections from each segment were analyzed semiquantitatively (Lucia Image Analysis software, Nikon), and levels of iron storage were graded by counting the number of positive cells per field of view.…”

Section: Histological Characterization Of Perivascular Fatmentioning

confidence: 99%

Macrophage Activation Is Responsible for Loss of Anticontractile Function in Inflamed Perivascular Fat

Withers

Agabiti-Rosei

Livingstone

et al. 2011

ATVB

110

103

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Objective-The aim of this study was to determine whether macrophages dispersed throughout perivascular fat are crucial to the loss of anticontractile function when healthy adipose tissue becomes inflamed and to gain an understanding of the mechanisms involved. Methods and Results-Pharmacological studies on in vitro small arterial segments from a mouse model of inducible macrophage ablation and on wild-type animals were carried out with and without perivascular fat using 2 physiological stimuli of inflammation: aldosterone and hypoxia. Both inflammatory insults caused a similar loss of anticontractile capacity of perivascular fat and increased macrophage activation. Aldosterone receptor antagonism and free radical scavengers were able to restore this capacity and reduce macrophage activation. However, in a mouse deficient of macrophages CD11b-diptheria toxin receptor (CD11b-DTR), there was no increase in contractility of arteries following aldosterone incubation or hypoxia. Conclusion-The presence and activation of macrophages in adipose tissue is the key modulator of the increase in contractility in arteries with perivascular fat following induction of inflammation. Despite multiple factors that may be involved in bringing about the vascular consequences of obesity, the ability of eplerenone to ameliorate the inflammatory effects of both aldosterone and hypoxia may be of potential therapeutic interest. Key Words: hypoxia Ⅲ microcirculation Ⅲ obesity Ⅲ inflammation O besity is set to reach epidemic levels in many countries, 1 predisposing individuals to an increased risk of type II diabetes, hypertension, and the inevitable consequences of circulatory disease. 2 The hallmark of this phenotype is an increase in the size of individual adipocytes as excess energy is stored, together with the recruitment and activation of macrophages and the release of cytokines as local inflammation ensues. 3,4 The effect on the vasculature can be profound, with loss of vasodilator adipokine bioavailability, increased tone, 5,6 and the development of the metabolic syndrome. 7

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“…Hypoleptinaemia has been described in catabolic conditions such as anorexia nervosa and diabetic ketoacidosis (12,14). Conversely, hyperleptinaemia has been found in obesity, hyperinsulinaemia, and nonalcoholic fatty liver disease (15,16). Intracellular leptin actions are mediated through the long isoform of the leptin receptor (Ob-R), a member of the class I cytokine receptor family.…”

mentioning

confidence: 99%

Effects of temporary low-dose galactose supplements in children aged 5–12 y with classical galactosemia: a pilot study

et al. 2015

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Background: Classical galactosemia is caused by severe galactose-1-phosphate uridyltransferase deficiency. Despite life-long galactose-restriction, many patients experience long-term complications. Intoxication by galactose and its metabolites as well as over-restriction of galactose may contribute to the pathophysiology. We provided temporary low-dose galactose supplements to patients. We assessed tolerance and potential beneficial effects with clinical monitoring and measurement of biochemical, endocrine, and IgG N-glycosylation profiles. Methods: We enrolled 26 patients (8.6 ± 1.9 y). Thirteen were provided with 300 mg of galactose/day followed by 500 mg for 2 wk each (13 patient controls). results: We observed no clinical changes with the intervention. Temporary mild increase in galactose-1-phosphate occurred, but renal, liver, and bone biochemistry remained normal. Patients in the supplementation group had slightly higher leptin levels at the end of the study than controls. We identified six individuals as "responders" with an improved glycosylation pattern (decreased G0/G2 ratio, P < 0.05). There was a negative relationship between G0/G2 ratio and leptin receptor sOb-R in the supplementation group (P < 0.05). conclusion: Temporary low-dose galactose supplementation in children over 5 y is well tolerated in the clinical setting. It leads to changes in glycosylation in "responders". We consider IgG N-glycan monitoring to be useful for determining individual optimum galactose intake.

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Leptin, free leptin index, insulin resistance and liver fibrosis in children with non-alcoholic fatty liver disease

Cited by 89 publications

References 52 publications

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

Macrophage Activation Is Responsible for Loss of Anticontractile Function in Inflamed Perivascular Fat

Effects of temporary low-dose galactose supplements in children aged 5–12 y with classical galactosemia: a pilot study

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