Key result
Western diet induces sex-specific vascular dysfunction in Akita mice, impairing male vasodilation and female insulin sensitivity.
Why the study?
Western diet consumption is common in Type 1 diabetes, prompting investigation into whether combining Type 1 diabetes and a Western diet impairs vascular function more than diet alone across sexes.
Does the combination of Type 1 diabetes and a Western diet cause sex-dependent vascular and proteomic remodeling compared to a Western diet alone in mice?
Does the combination of Type 1 diabetes and a Western diet cause sex-dependent vascular and proteomic remodeling compared to a Western diet alone in mice?
In a mouse model of Type 1 diabetes fed a Western diet, vascular injury mechanisms are sex-specific, highlighting the need to consider sex differences in diabetic vascular complications.
Sex-specific vascular effects in this T1D mouse model warrant clinical caution; leaves open translation to human sex differences.
Introduction and Objective: The consumption of a Western diet (WD) is common among individuals with Type 1 diabetes (T1D). We hypothesize that the combination of T1D and WD consumption has a more deleterious effect on vascular function than WD consumption alone, irrespective of sex. Methods: Male and female 8-week-old C57BL/6J and Akita mice were fed a WD for 20 weeks to induce obesity. Vascular responses were assessed in isolated abdominal aortas and mesenteric arteries. Passive pressure-diameter curves were determined in mesenteric arteries. Proteomic analyses were performed in the thoracic aorta. Results: Female Akitas mice were heavier than their corresponding controls, whereas male Akitas mice weighed less than male controls. Akita mice exhibited greater hyperglycemia than controls. Akita male mice exhibited impaired aortic vasodilation to SNP and increased vasoconstriction to the TXA2 agonist, U46619. In females, aortic vasodilation to insulin was reduced in Akita mice compared to WD-fed female controls. Both male and female Akitas showed increased modulus of elasticity in mesenteric arteries and higher calculated incremental pulse wave velocity at elevated pressures than their respective WD-fed controls. Proteomic network analysis suggests a dysregulation of metabolic (ketone body metabolism), inflammatory, and extracellular matrix pathways in Akita males compared to WD-fed controls. On the other hand, proteomic analysis of female cohorts did not reveal differentially expressed proteins. Conclusion: Akita mice exhibit sex-specific vascular dysfunction: males primarily show impaired endothelial-independent vasodilatory responses and molecular remodeling, whereas females display endothelial insulin resistance, indicating divergent mechanisms of diabetic vascular injury between the sexes. Disclosure J.H. Beltran Ornelas: None. T.J. Kelty: None. N. Imkaew: None. A. Udefa: None. F.I. Ramirez-Perez: None. R.S. Rector: None. L.A. Martinez-Lemus: None. C. Manrique Acevedo: None.
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ORNELAS et al. (2026) studied Type 1 diabetes and obesity. Type 1 diabetes (Akita mutation) combined with Western diet vs. C57BL/6J control mice fed a Western diet was evaluated on Vascular responses and proteomic remodeling. Akita mice fed a Western diet exhibited sex-specific vascular dysfunction compared to controls, with males showing impaired vasodilation and females displaying endothelial insulin resistance.
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