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Aging induced by D-galactose aggravates cardiac dysfunction via exacerbating mitochondrial dysfunction in obese insulin-resistant rats

  • Cherry Bo-Htay
  • Thazin Shwe
  • Louis Higgins
  • Siripong Palee
  • Krekwit Shinlapawittayatorn
  • Siriporn C Chattipakorn
  • Nipon ChattipakornEmail author
Original Article
  • 30 Downloads

Abstract

The prevalence of obesity and an aging population are increasing worldwide. Both obesity and aging are independently known to be associated with cardiac dysfunction. However, in obese insulin-resistant subjects, the effects of aging on metabolic status and cardiac and mitochondrial functions are not completely understood. We hypothesized that in the obese insulin-resistant condition, aging induced by D-galactose increases cardiac senescence markers and aggravates the impairment of metabolic parameters, cardiac and mitochondrial function, and increases oxidative stress, inflammation, apoptosis, and autophagy. Sixty-four male Wistar rats were fed with either normal diet (ND) or high-fat diet (HFD) for 12 weeks. Then, rats were divided into vehicle groups (0.9% NSS, subcutaneous injection (SC)) or D-galactose groups (150 mg/kg/day, SC). After 0.9%NSS or D-galactose treatment for 4 weeks and 8 weeks, metabolic and cardiac functions were determined. The heart was then removed to determine mitochondrial functions and enable biochemical studies. After 4 weeks of D-galactose injection, ND rats treated with D-galactose (NDD4), HFD rats treated with vehicle (HFV4), and HFD rats treated with D-galactose (HFD4) had reduced cardiac function, impaired cardiac mitochondrial function and autophagy, and increased oxidative stress, inflammation, and apoptosis. Interestingly, after 8 weeks, HFD rats treated with D-galactose (HFD8) had the worst impairment of cardiac and mitochondrial function, autophagy, and apoptosis in comparison to the other groups. Aging induced by D-galactose aggravated cardiac dysfunction in obese insulin-resistant rats through the worsening of cardiac mitochondrial function, autophagy, and increased apoptosis in a time-dependent manner.

Keywords

D-galactose Heart Mitochondria Obesity Aging 

Notes

Funding information

This work was supported by a NSTDA Research Chair Grant from the National Science and Technology Development Agency Thailand (NC), Thailand Research Fund Grants RTA6080003 (SCC), RSA5880015 (KS), RSA6180056 (SP), and the Chiang Mai University Center of Excellence Award (NC).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Aging Association 2019

Authors and Affiliations

  1. 1.Cardiac Electrophysiology Research and Training Center, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
  2. 2.Cardiac Electrophysiology Unit, Department of Physiology, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
  3. 3.Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai UniversityChiang MaiThailand

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