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Macrophages in the pathophysiology of NAFLD: The role of sex differences
Author(s) -
Ministrini Stefano,
Montecucco Fabrizio,
Sahebkar Amirhossein,
Carbone Federico
Publication year - 2020
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.13236
Subject(s) - nonalcoholic fatty liver disease , adipose tissue , steatosis , pathological , fatty liver , pathophysiology , sexual dimorphism , biology , inflammation , hormone , dysbiosis , physiology , medicine , bioinformatics , endocrinology , immunology , disease , gut flora
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial pathological condition, which recognizes a certain sexual dimorphism. Experimental and clinical studies provided evidence for a critical role of macrophages in NAFLD development and progression. Especially, liver‐resident macrophages (also known as Kupffer cells) are likely the common final pathway of several pro‐steatosic signals. A huge amount of danger‐associated molecular patterns recognized by Kupffer cells is provided within the liver by lipid and glucose toxicity. Other pro‐inflammatory signals come from surrounding tissues into the portal vein, directly to the liver: they come from dysfunctional adipocytes, adipose tissue macrophages and gut dysbiosis. These complex crosstalks are differently represented across sexes, as sexual hormones control many of these processes. Sexual dimorphism then modulates metabolic and inflammatory cascades driving the liver from a simple steatosis to NAFLD and beyond. Here, metabolic and inflammatory mechanisms underlying NALFD pathophysiology will be updated. A special attention will be paid to describe sex‐related differences that could provide insights for patient stratification and more tailored therapeutic approaches.