The hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis

Abstract

In fact, cardiovascular complications represent the leading cause of death in patients with NAFLD (15). How exactly NAFLD contributes to these diseases is unclear. Recent advances suggest that the liver may impact metabolism through the secretion of specific proteins. These proteins, often termed hepatokines, are secreted by the liver and mediate interorgan communication through autocrine, paracrine, and endocrine signaling (8, 16). Several hepatokines have been identified including fetuin A (17), fetuin B (18), fibroblast growth factor 21 (FGF21) (19), fibrinogen-like protein 1 (FGL1, also known as hepassocin) (20), follistatin (FST) (21-23), inhibin E (INHBE) (24, 25), leukocyte cell-derived chemotaxin 2 (LECT2) (26), retinol-binding protein 4 (RBP4) (27, 28), and selenoprotein P (SEPP1) (29). These hepatokines, whose expression is affected by conditions such as obesity and NAFLD, impact various organs to modulate glucose metabolism, lipid homeostasis, and inflammation. Studies in mice and humans indicate that altered hepatokine secretion promotes glucose intolerance, insulin resistance, NAFLD progression, and cardiovascular diseases (8, 16), making these proteins attractive targets to alleviate obesity-related metabolic disorders.