Obesity, fatty liver disease and intestinal microbiota

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations.

Microbiota dysbiosis: a new piece in the understanding of the carcinogenesis puzzle

“…Pro-inflammatory processes mediated by pathogen-associated molecular patterns (PAMPs) activate PRRs in various types of cells such as macrophages, myofibroblasts and epithelial cells that produce pro-inflammatory cytokines TNFa,. The TLR signals induce survival intracellular pathways mediated by activation of NFkB and signal transducer and activator of transcription 3 (STAT3) (Arslan, 2014;Beliz ario & Napolitano, 2015;Schwabe & Jobin, 2013). The TLRs can also induce tumour proliferation mediated by mitogens such as epiregulin, amphiregulin and hepatocyte growth factors.…”

“…The liver receives 70 % of its blood supply from the intestinal venous blood flow, and due to this close functional relationship between the liver and the gastrointestinal tract (gut-liver axis), there is constant exposure to nutrients, toxins, antigens derived from food, microbial products and microorganisms (Arslan, 2014;Hines et al, 2010;Ohtani, 2015). This organ is equipped with a wide repertoire of immune cells (macrophages, lymphocytes, natural killer cells, dendritic cells) whose function is to present the first line of defene against antigens derived from the intestine (Liaskou et al, 2012;Cesaro et al, 2011).…”

“…This organ is equipped with a wide repertoire of immune cells (macrophages, lymphocytes, natural killer cells, dendritic cells) whose function is to present the first line of defene against antigens derived from the intestine (Liaskou et al, 2012;Cesaro et al, 2011). The potential role of the intestinal microbiota in liver diseases has been known since 1921 (Arslan, 2014). The microbiome of the liver, although not fully understood, provides an example of how cancer may be promoted by dysbiotic microbiota through long-distance mechanisms (Schwabe & Jobin, 2013).…”

“…The microbiome, which is considered the 'forgotten organ' (Clemente et al, 2012) and our 'second genome' , contains a large number of genes that surpass the human genome in number by 100 times and perform key functions relevant for human health (Arslan, 2014;Schwabe & Jobin, 2013). The microbiome participates in the metabolism of nutrients and other environmental factors (Dietert & Silbergeld, 2015), vitamin synthesis (D'Argenio & Salvatore, 2015), inhibition of pathogenic growth (Kamada & Núñez, 2013), and maturation and maintenance of the immunological system (Schippa & Conte, 2014), while also ensuring a balance or homeostasis in the body (Arslan, 2014;Costello et al, 2009;Hooper & Macpherson, 2010;Schwabe & Jobin, 2013), stimulation of angiogenesis and regulation of host fat storage (Palmer et al, 2007).…”

Role of Janus Kinase 3 in Predisposition to Obesity-associated Metabolic Syndrome

“…Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, which describes a spectrum of liver pathology ranging from simple steatosis to hepatic cirrhosis (47,48). High-fat diets (HFD) are among the major environmental factor that induces pro-inflammatory signaling including through TLRs, which correlates with subsequent development of obesity, NAFLD, and insulin resistance (49,50).…”