Kupffer cells (KCs) are vital innate immune system cells in the
liver that participate in various metabolic states. Although several studies
have directly evaluated the role of KCs in different metabolic situations in
the liver, the definite characteristics of KCs remain unknown. KC depletion
techniques are used to determine the functions of KCs under metabolic
challenges; however, there is debate about their precise role even after
successful ablation. While some KC ablation studies showed improvement
in insulin resistance, fatty liver and metabolic parameters, other reports,
under the similar conditions, have not. Some studies have rationalized the
KCs dual actions in liver metabolic states by arguing their M1 and M2
biases. Activated M1 KCs secrete pro-inflammatory cytokines, growth factors and other
mediators to create inflammatory stress which initiates inflammatory signalling in hepatocytes
to disrupt the metabolic scenario. In contrast, M2 KCs generate anti-inflammatory cytokines
and mediators which improve glucose and lipid metabolic states within the liver.
Unfortunately, the M1/M2 bias does not provide reliable explanation as KCs depletion shows
strikingly different results. Despite many investigational studies on this topic, a
comprehensive review of these studies is lacking. This review attempts to address the issues
related with the dichotomy of KCs effects in lipid metabolism. This review not only warns the
future studies to carefully analyze the results that are drawn from KCs effects on lipid
metabolism but also suggest to evaluate animal models and KCs depletion techniques as an
equally important cofactor.
Keywords: Kupffer cells, immunometabolic, hepatic metabolism, ablation models, insulin resistance, fatty liver.
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