Boardman 2020 Am J Physiol Heart Circ Physiol

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Boardman NT, Pedersen TM, Rossvoll L, Hafstad AD, Aasum E (2020) Diet-induced obese mouse hearts tolerate an acute high fatty acid exposure that also increases ischemic tolerance. Am J Physiol Heart Circ Physiol 319:H682-93.

» PMID: 32795177

Boardman Neoma T, Pedersen Tina Myhre, Rossvoll Line, Hafstad Anne Dragoey, Aasum Ellen (2020) Am J Physiol Heart Circ Physiol

Abstract: An ischemic insult is accompanied by an acute increase in circulating fatty acid (FA), which can induce adverse changes related to cardiac metabolism/energetics. Although chronic hyperlipidemia contributes to the pathogenesis of obesity/diabetes-related cardiomyopathy, it unclear how these hearts are affected by an acute high FA-load. We hypothesize that adaptation to chronic FA exposure enhances the obese hearts' ability to handle an acute high FA-load. Diet-induced obese (DIO) and age-matched control (CON) mouse hearts were perfused in the presence of low or high FA-load (0.4 and 1.8 mM). Left ventricular (LV) function, FA oxidation rate, myocardial oxygen consumption and mechanical efficiency were assessed, followed by analysis of myocardial oxidative stress, mitochondrial respiration, protein acetylation as well as gene expression. Finally, ischemic tolerance was determined by examining LV functional recovery and infarct size. Under low FA conditions, DIO hearts showed mild LV dysfunction, oxygen wasting, mechanical inefficiency, and reduced mitochondrial OxPhos. High FA-load increased FA oxidation rates in both groups, but this did not alter any of the above parameters in DIO hearts. In contrast, CON hearts showed FA-induced mechanical inefficiency, oxidative stress and reduced OxPhos, as well as enhanced acetylation and activation of PPARα-dependent gene expression. While high FA-load did not alter functional recovery and infarct size in CON hearts, it increased ischemic tolerance in DIO hearts. Thus, this study demonstrates that acute FA-load affects normal and obese hearts differently, and that chronically elevated circulating FA levels render the DIO heart less vulnerable to the disadvantageous effects of an acute FA-load.

Keywords: Cardiac efficiency, Heart perfusion, Mitochondrial respiration, Pressure-volume Bioblast editor: Plangger M O2k-Network Lab: NO Tromsoe Larsen TS


Labels: MiParea: Respiration  Pathology: Obesity  Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS  Pathway: F, N  HRR: Oxygraph-2k 

2020-08