Growth Hormone and Insulin-Like Growth Factor 1 Regulation of Nonalcoholic Fatty Liver Disease

Dichtel, Laura E.; Córdoba-Chacón, José; Kineman, Rhonda D.

doi:10.1210/clinem/dgac088

Cited by 41 publications

(29 citation statements)

References 141 publications

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“…Numerous studies conducted on animal models have shown that mice with liver-specific GH receptor knock-out show severe hepatic steatosis along with upregulation of inflammatory cytokines and increased transaminases, signaling hepatocellular damage [28]. This finding is also confirmed in clinical studies conducted on an adult population with GH deficiency, in which it was shown that patients have a higher prevalence of MAFLD, and that GH replacement betters the characteristics of this damage [29,30].…”

Section: Discussionmentioning

confidence: 67%

The Role of the GH/IGF1 Axis on the Development of MAFLD in Pediatric Patients with Obesity

et al. 2022

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The anomalies of the Growth Hormone (GH)/Insulin-like Growth Factor-1 (IGF1) axis are associated with a higher prevalence of Metabolic Associated Fatty Liver Disease (MAFLD) and with a more rapid progression towards fibrosis, cirrhosis, and end-stage liver disease. A total of 191 adolescents with obesity [12–18 years] were consecutively enrolled between January 2014 and December 2020 and underwent liver biopsy to diagnose MAFLD severity. In all patients GH, IGF1 and Insulin-like Growth Factor-Binding Protein 3 (IGFBP3) were measured. Patients with inflammation and ballooning have significantly lower values of GH and IGF1 than those without (GH: 5.4 vs. 7.5 ng/mL; IGF1 245 vs. 284 ng/mL, p < 0.05). GH and IGF1 were also negatively correlated with fibrosis’ degree (r = −0.51, p = 0.001, and r = −0.45, p = 0.001, respectively). Only GH correlated with TNF-a (r = −0.29, p = 0.04) and lobular inflammation (r = −0.36, p = 0.02). At multivariate regression, both GH and IGF1 values, after adjustment for age, sex and BMI, were negatively associated with HOMA-IR but above all with fibrosis (GH→β = −2.3, p = 0.001, IGF1→β = −2.8, p = 0.001). Even in the pediatric population, a reduction of GH input in the liver directly promotes development of de novo hepatic lipogenesis, steatosis, fibrosis and inflammation. The possible role of recombinant GH administration in adolescents with obesity and severe MAFLD deserves to be studied.

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Section: Discussionmentioning

confidence: 67%

The Role of the GH/IGF1 Axis on the Development of MAFLD in Pediatric Patients with Obesity

et al. 2022

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“…NAFLD is becoming more well-recognized among young people. Cirrhosis can develop in up to 15% of people, although the illness can be stopped by losing weight, which reduces fatty infiltration and reverses biochemical alterations [ 13 – 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…BMI was evaluated by subdividing their body mass (kg) by the square of their tallness (in meters). By international standards, a person is considered obese if the BMI is more than the average BMI of the population (50 th percentile for age and sex) [ 12 , 13 ].…”

Section: Methodsmentioning

confidence: 99%

Non-alcoholic fatty liver disease: relation to juvenile obesity, lipid profile, and hepatic enzymes

et al. 2023

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The prevalence of juvenile obesity is increasing, reaching epidemic proportions, presenting a link not only to NAFLD (non-alcoholic fatty liver disease) but to abnormal lipid profiles and liver enzyme abnormalities. Liver ultrasonography is a sensitive and specific tool for the recognition of NAFLD. This study aims to assess the association between NAFLD and juvenile obesity and to determine the other related changes in a set of indicators, including lipid profile abnormalities and serum transaminases. The sample included 470 obese and 210 non-obese individuals aged 6–16. Anthropometric measures were assessed, with the serum lipid profile and liver transaminases, and abdominal ultrasonography was used to detect NAFLD. Fatty liver was found in 38% of the obese subjects and none of the non-obese subjects. Within obese subjects, mean body mass index (BMI) and waist circumference increased significantly in patients with NAFLD compared to those without fatty liver. Moreover, LDL (low-density lipoprotein), CHOL (cholesterol), and serum liver enzymes were significantly higher in the presence of NAFLD. In conclusion, NAFLD commonly associates with juvenile obesity, relating to obesity and the abnormal lipid profile (including elevated CHOL and LDL) among obese people, reflecting elevated liver transaminases, which increase the risk of cirrhosis.

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“…It has been shown that IGF-1 is able to inactivate hepatic stellate cells and induce their aging, thus limiting the development of fibrosis [35]. GH and IGF-1 regulate lipid metabolism and influence the development of steatosis, inflammation, and liver fibrosis in a certain way [36]. Thus, reduced IGF-1 production in the liver is not only the result of impaired liver function, but also plays an important role in the development of fibrosis.…”

Section: Scheme Of Neurohumoral Regulation Of Growth By the Gh/igf-1 ...mentioning

confidence: 99%

Growth Hormone and Insulin-like Growth Factor-1 in Children with Cholestatic Diseases and Pediatric Liver Transplantation

Gautier¹,

Шевченко²,

Цирульникова³

et al. 2023

Growth Hormone - Impact and Insights in Human Beings

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The growth hormone/insulin-like growth factor 1 (GH/IGF-1) system is the most important regulator of growth, regeneration, and metabolism in children and adults. Children with congenital cholestatic diseases have elevated GH blood levels, which is combined with growth failure and body mass deficit. Congenital cholestatic diseases lead to end-stage liver disease (ESLD), where GH bioavailability, mediated through IGF-1, is impaired. Blood IGF-1 levels are decreased due to impaired production by the liver. This study included 148 children up to 5 years (60 months) old with congenital cholestatic diseases. The patients underwent liver transplantation (LT) at a leading transplant center in Russia. The clinical significance of the GH/IGF-1 axis in pediatric liver recipients was investigated. Relationship between the patients’ GH/IGF-1 levels and anthropometric parameters was analyzed before and after LT. It was shown that LT leads to renewal/recovery of GH-IGF-1 regulation and improved anthropometric parameters (body height and body mass) in pediatric recipients.

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Growth Hormone and Insulin-Like Growth Factor 1 Regulation of Nonalcoholic Fatty Liver Disease

Cited by 41 publications

References 141 publications

The Role of the GH/IGF1 Axis on the Development of MAFLD in Pediatric Patients with Obesity

The Role of the GH/IGF1 Axis on the Development of MAFLD in Pediatric Patients with Obesity

Non-alcoholic fatty liver disease: relation to juvenile obesity, lipid profile, and hepatic enzymes

Growth Hormone and Insulin-like Growth Factor-1 in Children with Cholestatic Diseases and Pediatric Liver Transplantation

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