The angiopoietin-like protein 3: a hepatokine with expanding role in metabolism

Purpose of review Cumulating evidence are revealing roles of angiopoietin-like proteins (ANGPTLs) in lipid, glucose, and energy metabolism. In this review, we discuss the recent developments in understanding the specific role in metabolic processes of the liver-derived ANGPTL3. Recent findings Several groups have reported clinical and metabolic characterization of individuals with loss-of-function variants in ANGPTL3 showing familial combined hypolipidemia, a syndrome characterized by marked reduction of all plasma lipoproteins. Their findings indicate that in humans, ANGPTL3 has a broader action on apoB and apoA-I-containing lipoproteins, as well as on free fatty acid and adipose tissue metabolism. Summary The identification of loss-of-function ANGPTL3 mutation is shedding light on a possible role of ANGPTL3 at the crossroads of lipoproteins, fatty acids, and glucose metabolism, thus making ANGPTL3 an attractive protein to target the cardio-metabolic risk.