Distinct Hepatic Macrophage Populations in Lean and Obese Mice

Abstract

Obesity is a complex metabolic disorder associated with the development of non-communicable diseases such as cirrhosis, non-alcoholic fatty liver disease, and type 2 diabetes. In humans and rodents, obesity promotes hepatic steatosis and inflammation, which leads to increased production of pro-inflammatory cytokines and acute-phase proteins. Liver macrophages (resident as well as recruited) play a significant role in hepatic inflammation and insulin resistance (IR). Interestingly, depletion of hepatic macrophages protects against the development of high-fat-induced steatosis, inflammation, and IR. Kupffer cells (KCs), liver-resident macrophages, are the first-line defense against invading pathogens, clear toxic or immunogenic molecules, and help to maintain the liver in a tolerogenic immune environment. During high fat diet feeding and steatosis, there is an increased number of recruited hepatic macrophages (RHMs) in the liver and activation of KCs to a more inflammatory or M1 state. In this review, we will focus on the role of liver macrophages (KCs and RHMs) during obesity.

Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action

“…Interestingly, while we found that Fgf21 ‐/‐ mice had greater hepatic inflammation compared with WT mice fed a HFD for 12 weeks, a longer‐term study found no difference in hepatic inflammation between WT and Fgf21 ‐/‐ mice fed a high‐sucrose HFD for 52 weeks . The increased expression of inflammatory markers in liver of Fgf21 ‐/‐ mice may be due to activation of resident liver macrophages (Kupffer cells) or hepatic infiltration by newly recruited immune cells, both of which occur in obesity . Likewise, the increased expression of inflammatory markers in adipose tissue of Fgf21 ‐/‐ mice may be due to increased cytokine expression by adipocytes themselves, but it is more likely due to an increased presence of inflammatory immune cells .…”

Impact of A Cargo-Less Liposomal Formulation on Dietary Obesity-Related Metabolic Disorders in Mice

“…During obesity, there is an increased number of macrophages infiltration in adipose tissue and liver [ 34 , 35 ]. Increased Lipid influx and accumulation in those organs cause the activation of Kupffer cells (liver resident macrophages) and monocyte-derived macrophages.…”

“…Increased Lipid influx and accumulation in those organs cause the activation of Kupffer cells (liver resident macrophages) and monocyte-derived macrophages. Moreover, chronic hepatic inflammation leads to fatty liver disease and cirrhosis [ 35 ]. In the current study, macrophages were increased in both liver and fat tissue of HFD-PBS group, which were decreased with reduced inflammatory responses by UTS-001 treatment in both organs.…”

Macrophage Function in the Pathogenesis of Non-alcoholic Fatty Liver Disease: The Mac Attack

“…Collectively, the adaptation to latter events is central to preventing dissemination of microbes into peripheral circulation (5,39,40). In obesity, increased intestinal permeability, trafficking of bacteria into the gut lumen and LPS sensing (2,40,41) fuel KC activation and alter their function (42). In this context, activated KCs favor inflammatory responses that contribute to NAFLD pathogenesis (13).…”