Key result
High-fat diet reduces maximal endothelial vasorelaxation by ~11% in male mice, but not females.
Why the study?
Obesity and vascular dysfunction are independent and sexually dimorphic cardiovascular risk factors, prompting characterization of sex-specific changes in aortic immune cell profile and vascular function in early obesity.
Does a high-fat diet induce sex-specific changes in aortic inflammation and endothelial function in a mouse model of early obesity?
Does a high-fat diet induce sex-specific changes in aortic inflammation and endothelial function in a mouse model of early obesity?
Absolute Event Rate: 76.6% vs 86.1%
p-value: p=0.003
In a mouse model of early obesity, high-fat diet induces endothelial dysfunction and metabolic disturbances in males, while females exhibit delayed metabolic changes and a compensatory reduction in aortic proinflammatory monocytes.
Does not support clinical translation of sex-specific endothelial effects; leaves open human relevance of male-predominant impairment in early obesity models.
Obesity and vascular dysfunction are independent and sexually dimorphic risk factors for cardiovascular disease. Sex-specific changes in aortic immune cell profile and vascular function were characterized in a high fat diet (HFD)-induced model of early obesity. Six-week-old male and female C57BL/6 mice were fed a normal chow diet (NCD) or HFD for ten weeks. Metabolic parameters were measured weekly and fortnightly. At end point, aortic immune cell populations and endothelial function were characterized using flow cytometry and wire myography. HFD-male mice had higher bodyweight, blood cholesterol, fasting blood glucose and plasma insulin levels than NCD mice ( P < 0.05). HFD did not alter systolic blood pressure (SBP), glycated hemoglobin or blood triglycerides in either sex. HFD-females had delayed onset of obesity with a transient increase in fasting blood glucose at week 8 ( P < 0.05). Flow cytometry revealed fewer proinflammatory aortic monocytes in females fed a HFD compared to NCD. HFD did not affect aortic leukocyte populations in males. Conversely, HFD impaired endothelium-dependent vasorelaxation, but only in males. Overall, this highlights biological sex as a key factor determining vascular disease severity in early obesity.
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Tran et al. (2023) studied Early obesity / High-fat diet-induced obesity. High-fat diet (HFD) vs. Normal chow diet (NCD) was evaluated on Maximal endothelium-dependent vasorelaxation (Rmax) to acetylcholine in male mice (p=0.003). A 10-week high-fat diet impaired maximal endothelium-dependent vasorelaxation in male mice compared to normal chow (76.6% vs 86.1%, p=0.003), but did not impair vasorelaxation in female mice.
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