Parental obesity in an Alzheimer disease mouse model exacerbated cognitive decline and cardiac dysfunction in offspring, with male HFD-offspring showing reduced dP/dtmax (8,038 vs 18,704 mmHg/sec).
Does parental obesity exacerbate cognitive and cardiac dysfunction in lean offspring of an Alzheimer disease mouse model?
Parental obesity exacerbates Alzheimer's disease-related cognitive decline and cardiac dysfunction in offspring in a sex-specific manner, highlighting parental metabolic status as a risk factor.
Alzheimer disease (AD) is a growing health problem characterized by neurocognitive and cardiovascular dysfunction. Although parental obesity programs adverse cardiometabolic complications, including obesity, hypertension and cardiorenal dysfunction in their offspring, whether parental obesity worsens cardiac, metabolic, and cognitive function in lean offspring that are susceptible to AD (3xTg-AD mice) remains unclear. Male and female offspring from control diet-fed or high fat diet (HFD)-fed parents were examined at 26-28 weeks of age. Cognitive function was assessed by Morris Water Maze and New Object Recognition (NOR) tests, cardiac function by echocardiography and invasive hemodynamic measurements, and mitochondrial (MT) function by high-resolution respirometry in isolated cardiac fibers and brain cortex. AD offspring from obese parents (HFD-Offs) exhibited worse memory retention compared to AD offspring from lean parents (ND-Offs), whereas recognition memory assessed by NOR was not significantly different between groups although there was greater variability in HFD-Offs. Although systolic function by echocardiography was similar between groups, male HFD-Offs showed impaired diastolic relaxation with prolonged isovolumetric relaxation time (IVRT), while E/e’ remained unchanged. Left ventricular catheterization showed reduced indices of contractility and relaxation, including maximal and minimal rates of pressure changes: dP/dtmax (8,038±1011 vs. 18,704±183 mmHg/sec), dP/dtmin (-7,724±471 vs. -13,634±1139) and prolonged Tau (4.0±0.1 vs. 2.9±0.1) in HFD-Offs compared to ND-Offs. Male HFD-Offs exhibited reduced MT glucose and fatty acid oxidation in heart and brain. These findings indicate that parental obesity exacerbates AD-related cognitive decline and cardiac dysfunction in a sex-specific manner, suggesting parental metabolic status as an important determinant of AD-related cardiometabolic vulnerability.
Carmo et al. (Fri,) conducted a other in Alzheimer disease model (3xTg-AD mice). Parental high fat diet (HFD) vs. Parental control diet (ND) was evaluated on Cognitive function, cardiac function, and mitochondrial function. Parental obesity in an Alzheimer disease mouse model exacerbated cognitive decline and cardiac dysfunction in offspring, with male HFD-offspring showing reduced dP/dtmax (8,038 vs 18,704 mmHg/sec).