Abstract
BackgroundAdult growth hormone (GH) deficiency is associated with fatty liver disease and shows several features of the metabolic syndrome. Vice versa obesity is characterized as a state of low GH function. Here, we aimed to define the role of hepatic GH signaling and its metabolic consequences in non-alcoholic fatty liver disease.MethodsIn humans, GHR and IGF-1 levels were determined in liver samples of 29 obese patients with non-alcoholic steatohepatitis (NASH) or simple steatosis. Cellular effects of GH on insulin signaling were investigated in GH receptor (GHR) knockdown HepG2 cells.ResultsHepatic IGF-1 expression levels reflecting GH action were significantly lower and fasting glucose concentrations higher in patients with NASH than in patients with simple steatosis. GHR knockdown in hepatocytes resulted in a scenario of high glucose output displayed by reduced glycogen content, increased gluconeogenesis and diminished insulin signaling.ConclusionsOur data suggest that GH signaling in the liver is diminished in patients with NASH and associated with deteriorated hepatic insulin sensitivity and metabolic activity. Reduced hepatic GH action might contribute to insulin resistance in obese patients with NASH.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance characterized by reduced wholebody, adipose tissue and hepatic insulin sensitivity [1].Adult growth hormone deficiency (AGHD) is characterized by increased visceral obesity, dyslipidemia, premature atherosclerosis and increased mortality [2]
Our data suggest that GH signaling in the liver is diminished in patients with non-alcoholic steatohepatitis (NASH) and associated with deteriorated hepatic insulin sensitivity and metabolic activity
Reduced hepatic GH action might contribute to insulin resistance in obese patients with NASH
Summary
Non-alcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance characterized by reduced wholebody, adipose tissue and hepatic insulin sensitivity [1]. Adult growth hormone deficiency (AGHD) is characterized by increased visceral obesity, dyslipidemia, premature atherosclerosis and increased mortality [2]. Fatty liver disease is frequently found in patients with AGHD [3]. In some studies, GH and IGF-1 concentrations were decreased in patients with NAFLD [4, 5]. GH replacement could dramatically ameliorate steatosis, inflammation and fibrosis in a patient with AGHD and NASH [6]. Adult growth hormone (GH) deficiency is associated with fatty liver disease and shows several features of the metabolic syndrome. We aimed to define the role of hepatic GH signaling and its metabolic consequences in non-alcoholic fatty liver disease
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