Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

Abstract

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter of hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% of patients with non-alcoholic fatty liver disease (NAFLD). Due to liver dysfunction and the numerous metabolic changes that commonly accompany the condition (obesity, insulin resistance, type 2 diabetes, and metabolic syndrome), the secretion of organokines is modified, which may contribute to the pathogenesis or progression of the disease. In this sense, this study aimed to perform a review of the role of organokines in NASH. Thus, by combining descriptors such as NASH, organokines, oxidative stress, inflammation, insulin resistance, and dyslipidemia, a search was carried out in the EMBASE, MEDLINE-PubMed, and Cochrane databases of articles published in the last ten years. Insulin resistance, inflammation and mitochondrial dysfunction, fructose, and intestinal microbiota were factors identified as participating in the genesis and progression of NASH. Changes in the pattern of organokines secretion (adipokines, myokines, hepatokines, and osteokines) directly or indirectly contribute to aggravating the condition or compromise homeostasis. Thus, further studies involving skeletal muscle, adipose, bone, and liver tissue as endocrine organs are essential to better understand the modulation of organokines involved in the pathogenesis of NASH to advance in the treatment of this disease.

Bezafibrate Reduces Elevated Hepatic Fumarate in Insulin-Deficient Mice

“…The reduced regulators of inflammatory genes observed in the tissues of BEZ-treated animals are in line with previous findings, which showed that BEZ attenuates inflammatory processes [33,34]. FGF21 and adiponectin are described as insulin sensitizers, and a high leptin level is associated with insulin resistance [35]. BEZ activated FGF21 and adiponectin upstream regulators, as well as inhibited leptin.…”

Organokines in Rheumatoid Arthritis: A Critical Review

“…Its production is controlled by food intake, sex hormones, energy status, and inflammatory mediators. Leptin can also modulate both the innate and adaptive immune systems by activating proliferation and activation of macrophages and monocytes, regulating the cytotoxicity of natural killer cells, modulating neutrophils chemotaxis, and controlling T CD4, Th1 (T helper 1), and Th2 (T helper 2) cells’ phenotypes [ 11 , 99 , 100 , 101 ].…”

“…In turn, FGF-21 can decrease the activity of both cellular and humoral immune responses in individuals affected by RA. To maintain joint integrity, FGF-21 blocks the production of cathepsin K and metalloproteinases, especially the MMP-3 [ 11 , 122 , 123 , 124 , 125 , 126 ].…”

“…Fetuin-A is both an hepatokine and an adipokine although hepatocytes predominantly secrete it. This molecule is a multifunctional glycoprotein that imposes metabolic effects such as obesity, peripheral insulin sensitivity decrease, diabetes, and non-alcoholic fatty liver diseases, mainly at higher levels [ 11 ]. In autoimmune diseases such as AR and osteoarthritis, fetuin-A probably helps stimulate the production of pro-inflammatory cytokines by macrophages and other cells.…”

“…Considering the aforementioned information and that organokines can act combined to improve health or cause disease [ 11 ] and can play a role in RA, this study aimed to review the molecular and biochemical aspects of myokines, adipokines, hepatokines, and osteokines and their relationship with RA. In this scenario, this review will contribute to the emergence of new and modern diagnostic and therapeutic methods to the healthcare of RA patients, and to our knowledge, this is the first review to evaluate data about myokines, osteokines, adipokines, and hepatokines on RA pathophysiology.…”