Abstract
ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss-of-function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity-related metabolic abnormalities are modified by the ANGPTL4-E40K mutation. ANGPTL4-E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin-sensitivity. Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 × 10-9). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lip...Continue Reading
References
Jul 1, 1985·Diabetologia·D R MatthewsR C Turner
Sep 10, 1999·Diabetes Care·M Matsuda, R A DeFronzo
Jan 18, 2006·Nature Genetics·Andrew D SkolMichael Boehnke
Nov 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Valentina SukoninaGunilla Olivecrona
Feb 27, 2007·Nature Genetics·Stefano RomeoJonathan C Cohen
Aug 7, 2008·The Journal of Clinical Endocrinology and Metabolism·Carlos A Aguilar-SalinasFrancisco J Gómez-Pérez
Oct 23, 2008·Metabolism: Clinical and Experimental·Aaron R FolsomEric Boerwinkle
Nov 1, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Philippa J TalmudUNKNOWN HIFMECH Consortium
Mar 10, 2009·The Journal of Biological Chemistry·Wu YinJonathan C Cohen
May 3, 2013·Diabetes Care·Guy-Marino HinnouhoArchana Singh-Manoux
Dec 3, 2014·Atherosclerosis·Yuan LiChao-Ke Tang
Apr 8, 2016·Open Biology·Ren Zhang
Apr 15, 2016·The International Journal of Cardiovascular Imaging·Kayla Temov, Zhonghua Sun
May 27, 2016·Vascular Health and Risk Management·Peter P Toth
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Oct 11, 2016·Annals of the New York Academy of Sciences·Catherine M Phillips
Jun 18, 2017·Cell·Evan A BoyleJonathan K Pritchard
Dec 10, 2017·Diabetes Care·UNKNOWN American Diabetes Association
Mar 5, 2018·Diabetologia·Aafke W F JanssenSander Kersten
Mar 20, 2018·Journal of Clinical Lipidology·David S Olshan, Daniel J Rader
Mar 23, 2018·JCI Insight·Binod AryalCarlos Fernández-Hernando
Apr 6, 2018·Diabetologia·Brandon S J Davies
Jun 4, 2018·The Lancet. Diabetes & Endocrinology·Nathalie EckelMatthias B Schulze
Jun 15, 2018·Nature Communications·Viktoria GusarovaJesper Gromada
Citations
Jun 9, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Ilaria BarchettaMaria G Cavallo
Oct 3, 2020·International Journal of Molecular Sciences·Ilaria BarchettaMaria Gisella Cavallo
Jun 4, 2020·Journal of Lipid Research·Yan Q ChenRobert J Konrad
Feb 18, 2021·Journal of Translational Medicine·Zhoujie TongZhihao Wang
Apr 14, 2021·Scientific Reports·Kathryn M SpitlerBrandon S J Davies
Jul 14, 2021·The Journal of Clinical Investigation·Abhishek K SinghCarlos Fernandez-Hernando
Jan 29, 2022·Probiotics and Antimicrobial Proteins·Naif ALSuhaymiAbd El-Nasser Khattab