Macrophages as Key Players during Adipose Tissue–Liver Crosstalk in Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that could lead to serious health problems including liver failure, cancer, or death. The term NAFLD includes a spectrum of disease states with histological features ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). A key aspect within this research field is the identification of pathogenic factors that trigger inflammation, thus fueling the transition from nonalcoholic fatty liver to NASH. These inflammatory triggers may originate from within the liver as a result of innate immune cell activation and/or hepatocyte injury. Additionally, they may originate from other sites such as adipose tissue or the intestinal tract. In the current review, the authors will primarily focus on events within adipose tissue which may be of importance in triggering the disease progression. They specifically focus on the role of adipose tissue macrophages during NAFLD pathogenesis and how microenvironmental factors may shape their metabolic profile. They further dissect how redirecting the macrophage's metabolic profile alters their immunological functions. Finally, they discuss the opportunities and challenges of targeting macrophages to interfere in disease progression.

Association between Hemoglobin Glycation Index and NAFLD in Chinese Nondiabetic Individuals

“…Similarly, in population with type 2 diabetes participating to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we could get the same conclusion at the baseline [28]. Furthermore, recent studies had shown that even within the normal blood glucose level, the higher HGI level may identify subjects with an increased risk of insulin resistance, carotid atherosclerosis [18], and fatty liver [17,29]. e rst study demonstrated the relationship between NAFLD and HGI in 1,120 white individuals without diabetes was in 2017.…”

“…and liver cirrhosis, even hepatocellular carcinoma [29,31,32]. Furthermore, study had proved that methods reducing adipose tissue in ammation may improve insulin resistance in NAFLD [33].…”

Interleukin-10 Attenuates Liver Fibrosis Exacerbated by Thermoneutrality

“…Changes in the function of BAT at thermoneutrality might have an impact on HSC activation. Additionally, inflamed BAT also could release various factors into the systemic circulation, exposing liver tissue to inflammatory cytokines that might accelerate liver damage ( 38 ).…”

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

“…Other researchers focus on potential roles of the adipose tissue in NAFLD. In particular, adipose tissue macrophages were proposed as key players in NAFLD [146]. There is a general consensus that a large set of signaling molecules such as lipids, microRNAs, adipokines and immune-related compounds are released from adipose tissue into the portal vein triggering hepatic inflammation [146].…”

“…In particular, adipose tissue macrophages were proposed as key players in NAFLD [146]. There is a general consensus that a large set of signaling molecules such as lipids, microRNAs, adipokines and immune-related compounds are released from adipose tissue into the portal vein triggering hepatic inflammation [146]. In particular, the release of fatty acids from dysfunctional adipocytes results in liver parenchymal cell toxicity, which causes the ectopic accumulation of triglyceride-derived toxic metabolites increasing the activity of inflammatory pathways [147].…”