High-fat diet-induced metabolic syndrome in aged female mice caused significant diastolic failure compared to chow diet (E/A ratio 3.0 vs 1.7) and depressed ventilatory chemoreflex drive.
Does high-fat diet-induced metabolic syndrome worsen cardiorespiratory outcomes and sympathoexcitation in aging male and female SAMP8 mice?
Metabolic syndrome during aging accelerates cardiorespiratory alterations and increases female susceptibility to developing diastolic cardiac failure in a mouse model.
Absolute Event Rate: 3% vs 1.7%
Aging is associated with reduced cardiorespiratory performance and autonomic dysregulation (i.e. sympathoexcitation) both contributing to high cardiovascular risk and frailty. Importantly, a large portion of the aging population also suffers from metabolic syndrome (MS), a condition that independently increases the risk of cardiovascular diseases. Notably, previous studies linked MS to astrocytosis and neuroinflammation in adults. Whether MS hastens the development of cardiorespiratory distress during the aging process is completely unknown. Accordingly, we aim to determine if MS with aging differentially impacts cardiorespiratory outcomes in a sex- dependent manner, and whether these changes are associated with sympathoexcitation and neuroinflammation. Male and female 4 weeks old SAMP8 (Senescence Accelerated Mouse Prone 8) mice were fed with a high-fat diet (HFD, 60% kcal of fat) to induce MS or chow standard diet for 8 weeks. Echocardiography was used to analyze cardiac function. Tail-cuff and unrestrained whole-body plethysmography were used to assess blood pressure and breathing function, respectively. Mice were then anesthetized (urethane,80 mg/kg and α-chloralose, 8mg/kg) to record renal sympathetic nerve activity (RSNA) and for tissue extraction/fixation. Sholl analysis was performed on astrocytes within brainstem sympathetic control areas (i.e. RVLM) in fixed brains as an indirect measure of neuroinflammation. We found no significant changes related to MS in blood pressure between aged male and female groups. Contrarily, MS results in increased resting ventilation in eupneic conditions in both aged male and female groups. Interestingly, MS depressed ventilatory chemoreflex drive during the aging process as evidenced by significant reductions in the maximum ventilatory response to acute hypoxia (Minute ventilation: Males, 18.0±0.8 vs. 16.1±0.5; females, 23.8±1.1 vs. 20.6±1.5 ml/min/10g, chow vs. HFD). We also found that MS induces sympathoexcitation in aged males and females. Indeed, a ~2-fold increase in RSNA spikes were found in aged mice with MS compared to untreated groups. The later was accompanied by signs of neuroinflammation at the level of the RVLM. Astrocytes from both male and female aged mice with MS showed a rightward shift in morphology complexity towards a more complex state (i.e. reactive astrocyte). Despite similar respiratory and autonomic alterations, only aged female mice with MS developed cardiac dysfunction. MS aged female mice displayed significant diastolic failure compared to aged female mice fed with chow diet, indicated by a marked increase in E/A ratio (1.7 ± 0.22 vs. 3.0 ± 0.42, chow vs. HFD). Lastly, we found that MS during the aging process had a significant impact on frailty in both males and female mice. Our results suggest that MS during the aging process accelerates the development of cardiorespiratory alterations. Notably, our results also support the notion that MS increases female susceptibility to develop cardiac failure during the aging process. Funding: The Kansas Center for Metabolism and Obesity Research (KC-MORE #544258) and NIH R01HL176779. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
AlMarabeh et al. (Fri,) conducted a other in Metabolic syndrome during aging. High-fat diet (HFD) vs. Chow standard diet was evaluated on Diastolic function (E/A ratio) in aged female mice. High-fat diet-induced metabolic syndrome in aged female mice caused significant diastolic failure compared to chow diet (E/A ratio 3.0 vs 1.7) and depressed ventilatory chemoreflex drive.