title: Unexpected effects of voluntary exercise training on natriuretic peptide and receptor mRNA expression in the ob/ob mouse heart.
abstract: Regular exercise is generally recommended for the treatment of obesity and type 2 diabetes. Exercise reduces body weight, improves glycemic control and cardiovascular (CV) function. This study was designed to determine the impact of voluntary wheel running on the cardiac oxytocin (OT)-natriuretic peptide (NP) system and plasma CV risk factors in the ob/ob mouse, a model of insulin resistance coupled with severe obesity. Five-week-old male ob/ob mice and non-obese heterozygote control littermates were assigned to either a sedentary or running group. Voluntary running was performed using a wheel system for a period of 8 weeks. Compared to non-obese mice, daily running activity expressed in kilometers, was significantly lower in ob/ob mice. In these mice, voluntary running improved body weight, but exacerbated CV markers, including plasma glucose and triglyceride levels. OT receptor gene expression was decreased in hearts of ob/ob mice compared to non-obese mice, and no improvement in the expression of this receptor was observed after voluntary running. Hearts from ob/ob mice also expressed lower BNP mRNA, whereas no differences in A- and C-type NP were observed between non-obese and ob/ob mice. After voluntary running, a downregulation in the expression of all three NPs coupled with increased apoptosis was observed in ob/ob hearts. Our results show that voluntary exercise running activity was decreased in the ob/ob mouse. Surprisingly, this was associated with a worsening of common CV plasma markers, reduced expression of peptides linked to the cardioprotective OT-NP system, and increased expression of cardiac apoptotic markers.
authors.affiliation: Laboratory of Diabetes and Exercise Metabolism, Midwestern University, Glendale, AZ, USA. Electronic address: tbrode@midwestern.edu.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Broderick
authors.affiliation: Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de L'Université de Montréal-Hôtel-Dieu Research Centre, Montréal, Québec, Canada.
authors.forename: Donghao
authors.initials: D
authors.lastname: Wang
authors.affiliation: Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de L'Université de Montréal-Hôtel-Dieu Research Centre, Montréal, Québec, Canada.
authors.forename: Marek
authors.initials: M
authors.lastname: Jankowski
authors.affiliation: Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de L'Université de Montréal-Hôtel-Dieu Research Centre, Montréal, Québec, Canada.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gutkowska
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism*; D009043:Motor Activity; D009206:Myocardium / Q000378:metabolism*; D045265:Natriuretic Peptides / Q000235:genetics / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D012420:Running
chemical_list: D015415:Biomarkers; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D051275:Glucose Transporter Type 4; D045265:Natriuretic Peptides; C576074:OXTR protein, mouse; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; C495693:Slc2a4 protein, mouse
keywords: Glucose; Natriuretic peptides; Obesity; Oxytocin; Running; ob/ob