Exercise-Induced Release of Pharmacologically Active Substances and Their Relevance for Therapy of Hepatic Injury

Abstract

Chronic liver disease (CLD) features constant parenchymal injury and repair together with an increasing hepatic impairment, finally leading to fibrosis and cirrhosis and a heightened risk of hepatocellular carcinoma (HCC). Closely related to the rise in obesity, the worldwide prevalence of nonalcoholic fatty liver disease, the most common form of CLD, has reached an epidemic dimension and is estimated to afflict up to 46% of the general population, including more than one out of three U.S. citizens. Up to now there is no effective drug treatment available, which is why recommendations encompass both exercise programs and changes in dietary habits. Exercise is well-known for unleashing potent anti-inflammatory effects, which can principally counteract liver inflammation and chronic low-grade inflammation. This review article summarizes the underlying mechanisms responsible for the exercise-mediated anti-inflammatory effects, illustrates the application in animal models as well as in humans, and highlights the therapeutic value when possible. Based on the available results there is no doubt that exercise can even be beneficial in an advanced stage of liver disease and it is the goal of this review article to provide evidence for the therapeutic impact on fibrosis, cirrhosis, and HCC and to assess whether exercise might be of value as adjuvant therapy in the treatment of CLD. In principle, all exercise programs carried out in these high-risk patients should be guided and observed by qualified healthcare professionals to guarantee the patients’ safety. Nevertheless, it is also necessary to additionally determine the optimal amount and intensity of exercise to maximize its value, which is why further studies are essential.

Recent advances in understanding liver fibrosis: bridging basic science and individualized treatment concepts

“…In the general population, NAFLD is estimated to afflict up to 30% of the general population in the Western countries and is in most cases provoked by physical inactivity and excessive calorie intake 102 . In particular, NAFLD occurs in middle-aged subjects in association with obesity, hyperglycemia, dyslipidemia, and type 2 diabetes.…”

“…Currently, other pharmacotherapeutics for NAFLD and NASH such as GR-MD-02, which binds to the carbohydrate-binding domain of galectin-3, which is upregulated in cases of liver fibrosis and has an essential function in cell–cell interactions, angiogenesis, apoptosis, and macrophage activation, are also under investigation 115 . Beside these pharmaceutical treatment options, weight loss induced by lifestyle changes and controlled exercise have outstanding value in the treatment of fatty liver disease 102 . This was impressively demonstrated in a prospective study of 293 patients with histologically proven NASH, in which effective lifestyle changes to reduce weight over 52 weeks improved histologic features associated with NASH 116 .…”

The effect of His-tag and point mutation on the activity of irisin on MC3T3-E1 cells

“…Exercise acts as an important role on bone metabolic disorders in addition to pharmaceutical treatment. Besides mechanical interaction, it could remold bone tissue through regulating the expression of many factors such as tumor necrosis factor (1). Irisin is one of them and has attracted much attention since its discovery.…”

Current Status in Testing for Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)

“…However, a liver biopsy should be performed based on an individualized decision and is still the gold standard in scoring and grading of steatosis, inflammation, and fibrosis [12]. Although an ultimate therapy is still missing, beneficial effects on NAFLD/NASH progression are energy restriction, lifestyle changes, improved diets, and elevated physical activity [13]. In addition, in biopsy-proven NASH and fibrosis, medication with antiglycemic drugs, insulin sensitizers, synbiotics, or compounds interfering with fat metabolism or preventing oxidative stress have favorable effects on disease outcome [13,14].…”