Browse wiki

Jump to: navigation, search
Boardman 2018 MiPschool Tromso D3
Diseases Diabetes  + , Obesity  +
Event Oral  + , D3  +
Has abstract [[Image:MITOEAGLE-logo.jpg|left|100px|link
[[Image:MITOEAGLE-logo.jpg|left|100px|link=|COST Action MitoEAGLE]] An ischemic insult is associated with increased circulating fatty acids (FA) due to an adrenergic activation of adipose tissue lipolysis. Therefore, hearts will not only be challenged by hypoxia, but also by an acute FA-load, which has been shown to induce adverse cardiac effects such as mitochondrial dysfunction, oxidative stress, oxygen wasting and inefficiency. Although obesity is a contributing factor to the development of type 2 diabetes and heart failure it remains unclear if and how obesity-associated chronic hyperlipidemia affects the cardiac response to an acute FA-load. Thus, we have examined the effect of high FA on hearts from a murine model of obesity. Diet-induced obesity (DIO) was obtained by feeding 5-wk old male C57BL/6J mice obesogenic diet for 20 wks. Age-matched chow-fed mice were included as controls (CON). ''Ex vivo'' left ventricular (LV) function (working heart perfusions, n=8-11) and ischemic susceptibility (LV post-ischemic functional recovery and infarct size, Langendorff perfusions, n=12-15) were examined in hearts exposed to normal (0.35 mM) or high (1.8 mM) palmitate levels. We also assessed myocardial O<sub>2</sub> consumption (MVO<sub>2</sub>), FA oxidation and mechanical efficiency (n=12-15), as well as myocardial ROS content (DHE tissue staining) and mitochondrial respiration (high-resolution respirometry, ''n''=6-8). DIO mice demonstrated elevated plasma FA levels (0.37±0.03 vs 0.58±0.04 mM, p<0.01) and insulin resistance (4.4 fold higher HOMA-IR). They also developed diastolic dysfunction with only a mild systolic dysfunction. High FA perfusion did not alter LV function in neither CON nor DIO hearts. However, elevated FA decreased mechanical efficiency (due to increased MVO<sub>2</sub>, 28±2 vs 37±2 μmol/min/g, p<0.01), induced oxidative stress and reduced mitochondrial OXPHOS rate and coupling (RCR) in CON hearts. These FA-mediated changes were not found in DIO hearts. Furthermore, in contrast to CON hearts (where ischemic tolerance was not altered by the FA-load), DIO hearts exposed to high FA levels showed increased functional recovery (53±5 vs 36±5 % Rate-Pressure-Product, p<0.01) and decreased infarct size (47±2 vs 62±5%, p<0.02). This cardioprotective effect was corroborated in hearts from obese, type 2 diabetic (db/db) mice (54±6 vs 36±5 % recovery of RPP, p<0.05, and 55±5 vs72±2 % infarction, p<0.01, respectively). This study shows that hearts from obese/diabetic mice are resistant to the adverse effects an acute FA-load. Although dyslipidemia plays a role in the development of obesity/diabetes-mediated heart failure, we suggest that these hearts undergo adaptive changes where elevated FA levels exert cardioprotection.
elevated FA levels exert cardioprotection.  +
Has editor [[Beno M]]  + , [[Plangger M]]  +
Has title [[Image:MiPsocietyLOGO.JPG|left|90px|MiPsociety]] High fat-load induces cardioprotection in hearts from obese mice.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , Exercise physiology;nutrition;life style  +
Respiration and regulation Fatty acid  +
Tissue and cell Heart  +
Was published by MiPNetLab NO Tromsoe Larsen TS +
Was submitted in year 2018  +
Was submitted to event MiPschool Tromso-Bergen 2018 +
Was written by Boardman NT + , Pedersen TM + , Hafstad AD + , Rossvoll L + , Aasum E +
Categories Abstracts
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
07:01:43, 17 October 2018  +
hide properties that link here 
  No properties link to this page.
Enter the name of the page to start browsing from.