Overnourishment during lactation induces metabolic and haemodynamic heart impairment during adulthood

Nutr Metab Cardiovasc Dis. 2015 Nov;25(11):1062-9. doi: 10.1016/j.numecd.2015.07.009. Epub 2015 Jul 29.

Abstract

Aim: In this study, the effects of postnatal overfeeding on heart energy homoeostasis and cardiac haemodynamics in adult male Swiss mice were examined.

Methods and results: During the suckling period, the mice were divided into four groups of control or overfed pups in combination with baseline or ischaemia/reperfusion treatments (control group baseline, CGBL; overfed group baseline, OGBL; control group ischaemia/reperfusion, CGIR; and overfed group ischaemia/reperfusion, OGIR). End diastolic pressure (EDP), heart contraction speed (Max dP/dt), relaxation speed (Min dP/dt), isovolumetric relaxation time (Tau) and frequency by beats per minute (BPM) were measured. During baseline and ischaemia/reperfusion, key proteins such as AKT1, AKT2, AKT3, pAKT, adenosine monophosphate-activated protein kinase (AMPK), pAMPK, insulin receptor beta (IRβ), protein tyrosine phosphatase 1B (PTP1B), insulin receptor substrate 1 (IRS1), fatty acid binding protein (FABP), CD36, phosphoinositide 3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were studied. The expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 3 (UCP3) was studied as a marker of cardiac hypertrophy and energetic metabolism. Cardiac fibrosis was analyzed by quantifying collagen deposition, which is increased in the OGBL and OGIR groups compared with the control groups.

Conclusions: The OGBL group showed reduced EDP compared with the CGBL group and high Max dP/dt compared with the OGBL group. Ischaemia/reperfusion increased EDP and Min dP/dt in the intragroup comparison. By contrast, Tau and frequency were not significantly different among groups. The OGIR mice showed significant alterations in heart metabolism proteins, including AKT2, pAKT/AKT1, pAKT/AKT2, AMPK, pAMPK/AMPK, PTP1B, IRS1, FABP and CD36. Furthermore, alterations in ANP, BNP, CPT1 and UCP3 messenger RNA (mRNA) expression indicated hypertrophy and reduction in their efficiency, such that exclusive overnutrition in childhood induces a long-term effect on haemodynamics, metabolism and heart remodelling.

Keywords: Fatty acid; Heart metabolism; Insulin; Ischaemia/reperfusion injury; Postnatal overfeeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / genetics
  • Atrial Natriuretic Factor / metabolism
  • Blood Pressure
  • Female
  • Heart Failure / etiology*
  • Heart Failure / metabolism
  • Hemodynamics
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism
  • Intra-Abdominal Fat / metabolism
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Lactation*
  • Male
  • Mice
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Myocardial Contraction
  • Myocytes, Cardiac / metabolism
  • Overnutrition / complications*
  • Overnutrition / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Postnatal Care
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Uncoupling Protein 3

Substances

  • Insulin Receptor Substrate Proteins
  • Ion Channels
  • Irs1 protein, mouse
  • Mitochondrial Proteins
  • PPAR gamma
  • RNA, Messenger
  • Ucp3 protein, mouse
  • Uncoupling Protein 3
  • Atrial Natriuretic Factor
  • Phosphatidylinositol 3-Kinases
  • Receptor, Insulin
  • Akt1 protein, mouse
  • Akt2 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Ptpn1 protein, mouse