Ghrelin, leptin and insulin in cirrhotic children and adolescents: Relationship with cirrhosis severity and nutritional status

Dornelles, Cristina; Goldani, Helena Ayako Sueno; Wilasco, Maria Inês A.; Maurer, Rafael Lucyk; Kieling, Carlos Oscar; Porowski, Marilene; Ferreira, Cristina Targa; Santos, Jorge Luiz dos; Vieira, Sandra Maria Gonçalves; Silveira, Themis Reverbel da

doi:10.1016/j.regpep.2012.10.004

Cited by 13 publications

(14 citation statements)

References 29 publications

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“…Interestingly, Ghr was found to be dysregulated in patients with liver injuries 18 – 21 . Fasting Ghr levels were decreased in adults with cirrhosis, while DG was not changed or increased as compared to healthy volunteers 18 . In Child C cirrhosis patients though, Ghr levels were unchanged or elevated, independent of the etiology of liver disease 19 .…”

Section: Introductionmentioning

confidence: 99%

Ghrelin reverses ductular reaction and hepatic fibrosis in a rodent model of cholestasis

Petrescu

Grant

Williams

et al. 2020

Sci Rep

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The orexigenic peptide ghrelin (Ghr) stimulates hunger signals in the hypothalamus via growth hormone secretagogue receptor (GHS-R1a). Gastric Ghr is synthetized as a preprohormone which is proteolytically cleaved, and acylated by a membrane-bound acyl transferase (MBOAT). Circulating Ghr is reduced in cholestatic injuries, however Ghr’s role in cholestasis is poorly understood. We investigated Ghr’s effects on biliary hyperplasia and hepatic fibrosis in Mdr2-knockout (Mdr2KO) mice, a recognized model of cholestasis. Serum, stomach and liver were collected from Mdr2KO and FVBN control mice treated with Ghr, des-octanoyl-ghrelin (DG) or vehicle. Mdr2KO mice had lower expression of Ghr and MBOAT in the stomach, and lower levels of circulating Ghr compared to WT-controls. Treatment of Mdr2KO mice with Ghr improved plasma transaminases, reduced biliary and fibrosis markers. In the liver, GHS-R1a mRNA was expressed predominantly in cholangiocytes. Ghr but not DG, decreased cell proliferation via AMPK activation in cholangiocytes in vitro. AMPK inhibitors prevented Ghr-induced FOXO1 nuclear translocation and negative regulation of cell proliferation. Ghr treatment reduced ductular reaction and hepatic fibrosis in Mdr2KO mice, regulating cholangiocyte proliferation via GHS-R1a, a G-protein coupled receptor which causes increased intracellular Ca2+ and activation of AMPK and FOXO1, maintaining a low rate of cholangiocyte proliferation.

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Section: Introductionmentioning

confidence: 99%

Ghrelin reverses ductular reaction and hepatic fibrosis in a rodent model of cholestasis

Petrescu

Grant

Williams

et al. 2020

Sci Rep

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“…BDNF is involved in several complex processes and its expression is reduced by both stress and inflammation [28]. Inflammation associated with a poor nutritional status may result in decreased values of leptin in cirrhotic children [29], which when associated with insulin resistance may lead to decreased BDNF values [30]. …”

Section: Discussionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor in Children and Adolescents with Cirrhosis Due to Biliary Atresia

Wilasco

Cruz²,

Santetti³

et al. 2016

Ann Nutr Metab

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Background: The nutritional status in patients with cirrhosis is not so easy to assess properly. Considering the relationship between brain-derived neurotrophic factor (BDNF) and energy homeostasis, the main aim of this study was to evaluate the concentration of BDNF in children and adolescents with cirrhosis due to biliary atresia (BA) and correlate it with their nutritional status. Methods: Fifty-three children and adolescents with cirrhosis due to BA and 33 healthy controls were enrolled in this study. Nutritional status was evaluated using anthropometric parameters, and serum BDNF was measured by ELISA. Spearman coefficient was used to evaluate the correlation between variables. Results: In the cirrhosis group, 28.8% were undernourished and in the control group, 100% were well-nourished. BDNF median values for the control and cirrhosis group were 28.5 and 9.0 pg/ml respectively. BDNF and platelets were positively associated with both Standard Deviation Score (SDS) for height-for-age ratio and SDS for triceps skinfold thickness-for-age ratio. Conclusions: Considering these associations, BDNF may be an indirect biomarker of nutritional status in children and adolescents with chronic liver disease. Further studies must be conducted to clarify the role of BDNF in this population.

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“…After an overnight fast, venous blood was obtained in the morning for biochemical analysis as part of standard clinical follow-up. Serum albumin, bilirubin, prothrombin activity as well as the presence of ascites and grade of encephalopathy were assessed and Child-Pugh (C-P) classification [ 15 ] was used to determine the severity of the liver disease.…”

Section: Methodsmentioning

confidence: 99%

“…Anorexia can also be caused by a restricted diet, poor palatability of food. Malnutrition could also be attributed to abnormalities in absorption and digestion, along with the reduced hepatic synthesis of energy substrates [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Ghrelin Concentration in Patients With Primary Biliary Cirrhosis (PBC)

Naguib¹,

Fayed²,

Elkemary³

et al. 2021

Cureus

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Introduction: The appetite-modulating hormone ghrelin may have a role in the etiology of anorexia which is a serious concern in patients with primary biliary cirrhosis (PBC). This study aims to assess the difference in ghrelin level between cases of PBC and healthy controls matched for age and gender, and to evaluate the level of ghrelin in relation to clinical and laboratory findings among cases. Methods: Twenty patients with primary biliary cirrhosis and 30 healthy controls matched by gender and age were recruited. The severity of liver disease was determined using the Child-Pugh grading system. Clinical comorbidities such as a history of ascites, gastrointestinal bleeding, and encephalopathy were evaluated. A commercial enzyme-linked immunosorbent assay was used to measure total ghrelin. Results: PBC cases had a significantly higher average level of ghrelin (2305.3 ± 639.4) pg/mL compared to controls (682 ± 197.3) pg/mL. Furthermore, the minimum reported level in cases was 1258 pg/mL compared to 326 pg/mL in controls, while the maximum level nearly tripled the control’s maximum level. In PBC patients, plasma levels of total ghrelin showed a weak positive correlation with age, an inverse correlation with body mass index, and were not associated with gender. The level was significantly higher than those in the controls. Ghrelin was associated with the severity of cirrhosis. Levels of serum ghrelin were higher in patients with associated comorbidities such as a history of ascites, gastrointestinal bleeding, and encephalopathy. Conclusions: Our study demonstrated elevated serum ghrelin levels in patients with primary biliary cirrhosis. Serum ghrelin was associated with the degree of severity and the presence of related comorbidities. Patients with primary biliary cirrhosis remain anorexic and catabolic despite elevated ghrelin levels, suggesting tissue resistance to this anabolic peptide which could be crucial to understanding anorexia and cachexia in primary biliary cirrhosis.

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Ghrelin, leptin and insulin in cirrhotic children and adolescents: Relationship with cirrhosis severity and nutritional status

Cited by 13 publications

References 29 publications

Ghrelin reverses ductular reaction and hepatic fibrosis in a rodent model of cholestasis

Ghrelin reverses ductular reaction and hepatic fibrosis in a rodent model of cholestasis

Brain-Derived Neurotrophic Factor in Children and Adolescents with Cirrhosis Due to Biliary Atresia

Serum Ghrelin Concentration in Patients With Primary Biliary Cirrhosis (PBC)

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