https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33017 ~ATP), c) the rate of ATP production and d) flux through the creatine kinase (CK) reaction. At the lowest workload, the diastolic pressure-volume relationship was shifted upward in HFHS hearts, indicative of diastolic dysfunction, whereas systolic function was preserved. At this workload, the rate of ATP synthesis was decreased in HFHS hearts, and was associated with decreases in both [PCr] and ΔG_~ATP. Higher work demands unmasked the inability of HFHS hearts to increase systolic function and led to a further decrease in ΔG_~ATP to a level that is not sufficient to maintain normal function of sarcoplasmic Ca²⁺-ATPase (SERCA). While [ATP] was preserved at all work demands in HFHS hearts, the progressive increase in [ADP] led to a decrease in ΔG_~ATP with increased work demands. Surprisingly, CK flux, CK activity and total creatine were normal in HFHS hearts. These findings differ from dilated cardiomyopathy, in which the energetic deficiency is associated with decreases in CK flux, CK activity and total creatine. Thus, in HFHS-fed mice with MHD there is a distinct metabolic phenotype of the heart characterized by a decrease in ATP production that leads to a functionally-important energetic deficiency and an elevation of [ADP], with preservation of CK flux.]]> Wed 24 Nov 2021 15:52:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48338 per se, is sufficient to cause contractile dysfunction in MHD.]]> Tue 14 Mar 2023 17:22:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42207 2) during planned bariatric surgery. Compared with subcutaneous adipose tissue, visceral adipose tissue exhibited decreased complex II activity, which was restored with the reducing agent dithiothreitol (5 mM) (P < 0.01). A biotin switch assay identified that cysteine oxidative posttranslational modifications (OPTM) in complex II subunit A (succinate dehydrogenase A) were increased in visceral vs. subcutaneous fat (P < 0.05). Insulin treatment (100 nM) stimulated complex II activity in subcutaneous fat (P < 0.05). In contrast, insulin treatment of visceral fat led to a decrease in complex II activity (P < 0.01), which was restored with addition of the mitochondria-specific oxidant scavenger mito-TEMPO (10 µM). In a cohort of 10 subjects with severe obesity, surgical weight loss decreased OPTM and restored complex II activity, exclusively in the visceral depot. Mitochondrial complex II may be an unrecognized and novel mediator of insulin resistance associated with visceral adiposity. The activity of complex II is improved by weight loss, which may contribute to metabolic improvements associated with bariatric surgery.]]> Fri 26 Aug 2022 09:16:37 AEST ]]>