Heterozygous deficiency of endoglin decreases insulin and hepatic triglyceride levels during high fat diet

Daniel Beiroa; Amparo Romero-Picó; Carmen Langa; Carmelo Bernabeu; Miguel López; José M López-Novoa; Ruben Nogueiras; Carlos Diéguez

doi:10.1371/journal.pone.0054591

Heterozygous deficiency of endoglin decreases insulin and hepatic triglyceride levels during high fat diet

PLoS One. 2013;8(1):e54591. doi: 10.1371/journal.pone.0054591. Epub 2013 Jan 15.

Authors

Daniel Beiroa¹, Amparo Romero-Picó, Carmen Langa, Carmelo Bernabeu, Miguel López, José M López-Novoa, Ruben Nogueiras, Carlos Diéguez

Affiliation

¹ Department of Physiology, School of Medicine-CIMUS - Instituto de Investigaciones Sanitarias (IDIS), CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), University of Santiago de Compostela, Santiago de Compostela, A Coruña, Spain.

Abstract

Endoglin is a transmembrane auxiliary receptor for transforming growth factor-beta (TGF-beta) that is predominantly expressed on proliferating endothelial cells. It plays a wide range of physiological roles but its importance on energy balance or insulin sensitivity has been unexplored. Endoglin deficient mice die during midgestation due to cardiovascular defects. Here we report for first time that heterozygous endoglin deficiency in mice decreases high fat diet-induced hepatic triglyceride content and insulin levels. Importantly, these effects are independent of changes in body weight or adiposity. At molecular level, we failed to detect relevant changes in the insulin signalling pathway at basal levels in liver, muscle or adipose tissues that could explain the insulin-dependent effect. However, we found decreased triglyceride content in the liver of endoglin heterozygous mice fed a high fat diet in comparison to their wild type littermates. Overall, our findings indicate that endoglin is a potentially important physiological mediator of insulin levels and hepatic lipid metabolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Body Weight / genetics
Diet, High-Fat*
Endoglin
Energy Metabolism
Glucose / metabolism
Heterozygote*
Insulin / metabolism*
Intracellular Signaling Peptides and Proteins / deficiency
Intracellular Signaling Peptides and Proteins / genetics*
Liver / metabolism*
Male
Mice
Mice, Knockout
Phenotype
Signal Transduction
Triglycerides / metabolism*

Substances

Endoglin
Eng protein, mouse
Insulin
Intracellular Signaling Peptides and Proteins
Triglycerides
Glucose

Grants and funding

This work has been supported by grants from Ministerio de Educacion y Ciencia (CD: BFU2011; ML: RyC-2007-00211; RN: RYC-2008-02219 and SAF2009-07049; GS: RYC-2009-04972, SAF2010-15881 and SAF2010-19347; JML-N: SAF2010-15881; CB: SAF2010-61827), Xunta de Galicia (ML: 10PXIB208164PR and RN: 2010/14), Junta de Castilla y León (Excellence Group GR100) Fondo Investigationes Sanitarias (ML: PS09/01880), Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn), CIBER de Enfermedades Raras (CIBERER) and Red de Investigación Cooperativa en Enfermedades Renales (REDinREN). CIBERobn, CIBERER and RETIC REDinREN are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain supported by FEDER funds. The research leading to these results has also received funding from the European Community's Seventh Framework Programme under grant agreements (CD, ML and RN: FP7/2007-2013: n° 245009: NeuroFAST, and RN: ERC-2011-StG-OBESITY53-281408). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.