INSIGHT ON ANGPTL3 IMPACT ON HEPATIC METABOLISM AND FUNCTION
type: CreativeWork
description: Background and aim Angiopoietin-like protein 3 (ANGPTL3) is a hepatokine, that inhibits lipoprotein and endothelial lipase with ANGPTL8, sparing the hydrolyzation of VLDLs. Its deficiency leads to higher lipases activation, resulting into hypolipidemia and protection from cardiometabolic risk. While the role of circulating ANGPTL3 on lipases has been well established, its effect on hepatic homeostasis and metabolism is still unclear. This work aims to unravel the autocrine effects of ANGPTL3 within the liver and its systemic impact on peripheral organs. The liver plays a key role in systemic metabolism, substrates management and partitioning, xenobiotics clearance, energy production and lipoproteins synthesis. Absence of hepatic ANGPTL3 - master regulator of lipids partitioning - may therefore alter essential liver functions. Methods Angptl3 full knockout (Angptl3KO) and wild-type mice were utilized. In vivo observations included indirect calorimetry, biochemical profiling of glucose lipids and glucose levels and metabolic challenges comprised insulin, pyruvate/lactate and triglycerides (TG) tolerance tests. After 16-18 weeks on either standard chow diet or high-fat (HFD) diet, mice were sacrificed for blood and organs collection. Ex vivo analyses included transcriptomic analysis of liver, skeletal muscle and heart, as well as metabolomic analysis on liver samples. Spatial gene expression profiling of the liver was evaluated. Obesity development was assessed through histology and immunophenotyping of blood, liver and bone marrow through flow cytometry. Results Angptl3KO mice exhibited persistent hypolipidemia regardless of feeding status, with higher TG clearance and a reduced hepatic lipoprotein production, without signs of hepatic steatosis. Compared to controls, Angptl3KO mice on a chow diet showed altered basal metabolism and a higher susceptibility to fasting, as highlighted by higher gluconeogenesis and as supported by transcriptomic and metabolomic data. This…
abstract: Background and aim Angiopoietin-like protein 3 (ANGPTL3) is a hepatokine, that inhibits lipoprotein and endothelial lipase with ANGPTL8, sparing the hydrolyzation of VLDLs. Its deficiency leads to higher lipases activation, resulting into hypolipidemia and protection from cardiometabolic risk. While the role of circulating ANGPTL3 on lipases has been well established, its effect on hepatic homeostasis and metabolism is still unclear. This work aims to unravel the autocrine effects of ANGPTL3 within the liver and its systemic impact on peripheral organs. The liver plays a key role in systemic metabolism, substrates management and partitioning, xenobiotics clearance, energy production and lipoproteins synthesis. Absence of hepatic ANGPTL3 - master regulator of lipids partitioning - may therefore alter essential liver functions. Methods Angptl3 full knockout (Angptl3KO) and wild-type mice were utilized. In vivo observations included indirect calorimetry, biochemical profiling of glucose lipids and glucose levels and metabolic challenges comprised insulin, pyruvate/lactate and triglycerides (TG) tolerance tests. After 16-18 weeks on either standard chow diet or high-fat (HFD) diet, mice were sacrificed for blood and organs collection. Ex vivo analyses included transcriptomic analysis of liver, skeletal muscle and heart, as well as metabolomic analysis on liver samples. Spatial gene expression profiling of the liver was evaluated. Obesity development was assessed through histology and immunophenotyping of blood, liver and bone marrow through flow cytometry. Results Angptl3KO mice exhibited persistent hypolipidemia regardless of feeding status, with higher TG clearance and a reduced hepatic lipoprotein production, without signs of hepatic steatosis. Compared to controls, Angptl3KO mice on a chow diet showed altered basal metabolism and a higher susceptibility to fasting, as highlighted by higher gluconeogenesis and as supported by transcriptomic and metabolomic data. This…
author: TERENGHI, OTTAVIA
language: eng
keywords: Lipid, metabolism, liver, omic, cardiometabolic disorders, Settore BIOS-11/A - Farmacologia
date published: 2025-12-16
date modified: 2026-07-27T20:19:12Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1199595