Targeted delivery of HGF to the skeletal muscle improves glucose homeostasis in diet-induced obese mice.
Hepatocyte growth factor (HGF) is a cytokine that increases glucose transport ex vivo in skeletal muscle. The aim of this work was to decipher the impact of whether conditional overexpression of HGF in vivo could improve glucose homeostasis and insulin sensitivity in mouse skeletal muscle. Following tetracyclin administration, muscle HGF levels were augmented threefold in transgenic mice (SK-HGF) compared to control mice without altering plasma HGF levels. In conditions of normal diet, SK-HGF mice showed no differences in body weight, plasma triglycerides, blood glucose, plasma insulin and glucose tolerance compared to control mice. Importantly, obese SK-HGF mice exhibited improved whole-body glucose tolerance independently of changes in body weight or plasma triglyceride levels compared to control mice. This effect on glucose homeostasis was associated with significantly higher (∼80%) levels of phosphorylated protein kinase B in muscles from SK-HGF mice compared to control mice. In conclusion, muscle expression of HGF counteracts obesity-mediated muscle insulin resistance and improves glucose tolerance in mice.
Research Unit, University Hospital "Puerta del Mar", Cádiz, Spain.
Viviana
V
Sanchez-Encinales
Research Unit, University Hospital "Puerta del Mar", Cádiz, Spain.|Instituto de Genética y Biología Molecular, Universidad de Valladolid-CSIC, Valladolid, Spain.
Irene
I
Cozar-Castellano
Diabetes, Obesity and Metabolism Institute, The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, Atran 5 Box 1152, 1 Gustave L. Levy Place, New York, NY, 10029, USA. adolfo.garcia-ocana@mssm.edu.
Adolfo
A
Garcia-Ocaña
Research Unit, University Hospital "Puerta del Mar", Cádiz, Spain. perdomogm@yahoo.com.|School of Environmental Sciences and Biochemistry, University of Castilla-La Mancha, Science-Technology Campus in the Old Weapons Factory, Sabatini Building, Avenue of Charles III, s/n, 45071, Toledo, Spain. perdomogm@yahoo.com.
Germán
G
Perdomo
D000818:Animals; D001786:Blood Glucose; D059305:Diet, High-Fat / Q000009:adverse effects; D018390:Gene Targeting; D005947:Glucose / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D006706:Homeostasis; D007328:Insulin / Q000502:physiology; D050356:Lipid Metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D015533:Transcriptional Activation
D001786:Blood Glucose; C553307:HGF protein, mouse; D007328:Insulin; D017228:Hepatocyte Growth Factor; D005947:Glucose
Hepatocyte growth factor; Insulin resistance; Obesity; Skeletal muscle