Metabolic syndrome reduces cerebral blood flow more in women than men
Authors: Banks Nile , Carter Katrina , Wannebo Brett , Kellawan Mikhail , Al-Subu Awni , Hagan Scott , Serlin Ronald 
Published: May 2024

One in three adults in the United States suffers from metabolic syndrome (MetSyn), a state of insulin resistance associated with reduced cerebral blood flow (CBF) and increased risk of stroke and neurologic diseases. Notably, females are at greater risk for cardiovascular and metabolic complications derived from insulin resistance. Still, it remains unclear whether the reduction in CBF seen in MetSyn is sex-specific or uniform between various brain regions. Additionally, fasting triglyceride (TG) levels are stronger predictors of cognitive disease in females than in males. However, little data exist examining the relationship between TG and CBF in females with MetSyn. Therefore, we aimed to examine the interaction between sex and MetSyn on global and regional CBF in young adults and to explore the relationship between fasting TG levels and CBF. We predict that males and females with MetSyn will have lower global and regional CBF compared to healthy controls of the same sex, but to a greater extent in females with MetSyn. Additionally, we predict fasting TG levels will have stronger relationships with CBF in females than in males with MetSyn. Twenty-five healthy controls (CON; 7 females; 24 ± 4 y) and 13 individuals with MetSyn (5 females; 27 ± 8 y) completed this study. Subjects were unmedicated, and females were studied on days 1-5 of their menstrual cycle. A metabolic panel, blood pressure, and waist circumference were collected in a fasted state. Magnetic resonance imaging (MRI, 3 Tesla) with arterial spin labeling was used to quantify global and regional CBF. Two-way (Group x Sex) linear models with Shaffer’s correction and Tukey adjusted post hocs were used to determine differences in CBF. In the MetSyn groups, Pearson correlation coeffcients were assessed between fasting TG levels and each global and regional CBF value. Global CBF was greater in female CON compared to all groups (p ≤ 0.01), and male CON had greater CBF than male MetSyn (p = 0.03), whereas there was no difference between male and female MetSyn (p = 0.43). Regional analyses resulted in the same pattern of between-group differences in the parietal lobe (p = 0.03), the precuneus (p = 0.01), and the frontal lobe (p = 0.01), outside of a nonsignificant difference between male CON and male MetSyn in the frontal lobe (p = 0.12). No interactions existed for the temporal lobe, occipital lobe, or thalamus (p ≥ 0.06). In females with MetSyn, fasting TG levels were moderately negatively correlated with CBF (r = -0.65), whereas a moderate positive relationship existed in males with MetSyn (r = 0.71). These data suggest that MetSyn reduces CBF to a greater extent in females than males, abolishing sex-dependent differences in CBF present in healthy young adults. While female sex is protective against cardiovascular disease in healthy young adults, this is not the case in individuals with MetSyn. Additionally, males and females with MetSyn had opposing relationships between fasting TG levels and CBF. These findings may help explain the greater cardiovascular risk in females with insulin resistance. American Diabetes Association (ADA1-16-ICTS-099 and ADA 1-12-IN-39); Clinical and Translational Science Award program (UL1TR002373); Wisconsin National Primate Research Center (P51OD011106). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.