Unexpected effects of voluntary exercise training on natriuretic peptide and receptor mRNA expression in the ob/ob mouse heart

Regul Pept. 2014 Jan 10:188:52-9. doi: 10.1016/j.regpep.2013.12.005. Epub 2013 Dec 21.

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.

Keywords: Glucose; Natriuretic peptides; Obesity; Oxytocin; Running; ob/ob.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers / metabolism
  • Body Weight
  • GATA4 Transcription Factor / genetics
  • GATA4 Transcription Factor / metabolism
  • Gene Expression*
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Male
  • Mice
  • Mice, Obese / metabolism*
  • Motor Activity
  • Myocardium / metabolism*
  • Natriuretic Peptides / genetics
  • Natriuretic Peptides / metabolism*
  • Physical Conditioning, Animal
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Oxytocin / genetics
  • Receptors, Oxytocin / metabolism
  • Running

Substances

  • Biomarkers
  • GATA4 Transcription Factor
  • Gata4 protein, mouse
  • Glucose Transporter Type 4
  • Natriuretic Peptides
  • OXTR protein, mouse
  • RNA, Messenger
  • Receptors, Oxytocin
  • Slc2a4 protein, mouse