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Sex-dependent differences in central artery haemodynamics in normal and fibulin-5 deficient mice: implications for ageing.

ABSTRACT: Mouse models provide unique opportunities to study vascular disease, but they demand increased experimental and computational resolution. We describe a workflow for combining in vivo and in vitro biomechanical data to build mouse-specific computational models of the central vasculature including regional variations in biaxial wall stiffness, thickness and perivascular support. These fluid-solid interaction models are informed by micro-computed tomography imaging and in vivo ultrasound and pressure measurements, and include mouse-specific inflow and outflow boundary conditions. Hence, the model can capture three-dimensional unsteady flows and pulse wave characteristics. The utility of this experimental-computational approach is illustrated by comparing central artery biomechanics in adult wild-type and fibulin-5 deficient mice, a model of early vascular ageing. Findings are also examined as a function of sex. Computational results compare well with measurements and data available in the literature and suggest that pulse wave velocity, a spatially integrated measure of arterial stiffness, does not reflect well the presence of regional differences in stiffening, particularly those manifested in male versus female mice. Modelling results are also useful for comparing quantities that are difficult to measure or infer experimentally, including local pulse pressures at the renal arteries and characteristics of the peripheral vascular bed that may differ with disease.

SUBMITTER: Cuomo F

PROVIDER: S-EPMC6364598 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Sex-dependent differences in central artery haemodynamics in normal and fibulin-5 deficient mice: implications for ageing.

Cuomo Federica F Ferruzzi Jacopo J Agarwal Pradyumn P Li Chen C Zhuang Zhen W ZW Humphrey Jay D JD Figueroa C Alberto CA

Proceedings. Mathematical, physical, and engineering sciences 20190109 2221

Mouse models provide unique opportunities to study vascular disease, but they demand increased experimental and computational resolution. We describe a workflow for combining in vivo and in vitro biomechanical data to build mouse-specific computational models of the central vasculature including regional variations in biaxial wall stiffness, thickness and perivascular support. These fluid-solid interaction models are informed by micro-computed tomography imaging and in vivo ...[more]

PMID: 30760948

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Project description:Background/objectivesCentral insulin action influences cognitive processes, peripheral metabolism, and eating behavior. However, the contribution of obesity and sex on central insulin-mediated neural food cue processing still remains unclear.Subjects/methodsIn a randomized within-participant design, including two visits, 60 participants (30 women, BMI 18-32 kg/m2, age 21-69 years) underwent a functional MRI task measuring blood oxygen level-dependent (BOLD) signal in response to visual food cues after intranasal insulin or placebo spray administration. Central insulin action was defined as the neural BOLD response to food cues after insulin compared to placebo administration. Afterwards, participants were asked to rate the food cues for desire to eat (i.e., wanting rating). For statistical analyses, participants were grouped according to BMI and sex.ResultsFood cue reactivity in the amygdala showed higher BOLD activation in response to central insulin compared to placebo. Furthermore, women with overweight and obesity and men of normal weight showed higher BOLD neural food cue responsivity to central insulin compared to placebo. Higher central insulin action in the insular cortex was associated with better peripheral insulin sensitivity and higher cognitive control. Moreover, central insulin action in the dorsolateral prefrontal cortex (DLPFC) revealed significant sex differences. In response to central insulin compared to placebo, men showed lower DLPFC BOLD activity, whereas women showed higher DLPFC activity in response to highly desired food cues. On behavioral level, central insulin action significantly reduced hunger, whereas the desire to eat, especially for low caloric food cues was significantly higher with central insulin than with placebo.ConclusionsObesity and sex influenced the central insulin-mediated neural BOLD activity to visual food cues in brain regions implicated in reward and cognitive control. These findings show that central insulin action regulates food response differentially in men and women, which may have consequences for metabolism and eating behavior.

Dataset Information

Sex-dependent differences in central artery haemodynamics in normal and fibulin-5 deficient mice: implications for ageing.

Publications

Sex-dependent differences in central artery haemodynamics in normal and fibulin-5 deficient mice: implications for ageing.

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