Insulin-Like Growth Factor-1 Deficiency and Cirrhosis Establishment

Abstract

Cirrhosis represents the final stage of chronic liver damage, which can be due to different factors such as alcohol, metabolic syndrome with liver steatosis, autoimmune diseases, drugs, toxins, and viral infection, among others. Nowadays, cirrhosis is an important health problem and it is an increasing cause of morbidity and mortality, being the 14th most common cause of death worldwide. The physiopathological pathways that lead to fibrosis and finally cirrhosis partly depend on the etiology. Nevertheless, some common features are shared in this complex mechanism. Recently, it has been demonstrated that cirrhosis is a dynamic process that can be altered in order to delay or revert fibrosis. In addition, when cirrhosis has been established, insulin-like growth factor-1 (IGF-1) deficiency or reduced availability is a common condition, independently of the etiology of chronic liver damage that leads to cirrhosis. IGF-1 deprivation seriously contributes to the progressive malnutrition of cirrhotic patient, increasing the vulnerability of the liver to establish an inflammatory and oxidative microenvironment with mitochondrial dysfunction. In this context, IGF-1 deficiency in cirrhotic patients can justify some of the common characteristics of these individuals. Several studies in animals and humans have been done in order to test the replacement of IGF-1 as a possible therapeutic option, with promising results.

An Overview of the Molecular Mechanisms Contributing to Musculoskeletal Disorders in Chronic Liver Disease: Osteoporosis, Sarcopenia, and Osteoporotic Sarcopenia

“…In addition, IGF-1 reduced bone resorption through the OPG and RANKL system [ 86 ]. In end-stage liver disease, hepatocellular dysfunction and reduced GH receptors lead to low serum IGF-1 levels, subsequently causing osteoporosis [ 87 ]. Insulin, an important hormone associated with NAFLD, also affects bone remodeling by activating collagen synthesis and stimulating osteoblast proliferation and differentiation [ 88 ].…”

Somatotropic Axis Dysfunction in Non-Alcoholic Fatty Liver Disease: Beneficial Hepatic and Systemic Effects of Hormone Supplementation

“…In contrast, direct supplementation with IGF-1 has insulin sensitizing effects mainly mediated by the suppression of GHRH on a pituitary level and systemic reduction of GH levels, thus reducing its negative effects [ 23 ]. IGF-1 has been additionally demonstrated to have hepatoprotective effects in studies based on animal models of hepatic cirrhosis, including the decrease of oxidative stress, insulin resistance, hepatocellular apoptosis and fibrogenesis [ 26 , 28 , 29 , 30 ]. Given the metabolic differences in the effects of GH and IGF-1, it is relevant to compare the effects of supplementation with each of these hormones in NAFLD.…”

NAFLD in Some Common Endocrine Diseases: Prevalence, Pathophysiology, and Principles of Diagnosis and Management

“…Based on the metabolic effects of the GH–IGF-1 axis on the adipose tissue and the liver, different pathogenic mechanisms were suggested as a possible link between GHD and NAFLD [150,151], notably including insulin resistance, which is a shared common denominator of both diseases. It was repeatedly observed that mouse models with liver-specific deletion of GH receptor (GHRLD) develop insulin resistance, hepatic steatosis, dyslipidemia, and increased de novo lipogenesis [152,153].…”