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Diet Composition Drives Distinct Autonomic and Cardiovascular Outcomes
Abstract   Peer reviewed

Diet Composition Drives Distinct Autonomic and Cardiovascular Outcomes

Donald Morgan, Deng-Fu Guo, Meghan Naber, Young Eun Cho and Kamal Rahmouni
Physiology (Bethesda, Md.), Vol.41(S1)
05/2026
DOI: 10.1152/physiol.2026.41.S1.2300949

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Abstract

Abstract only The Western diet—characterized by high levels of saturated fats, refined sugars, and low fiber—drives the epidemic of obesity and cardiovascular disease, including hypertension. High-fat diet (HFD) and high-fat high-sucrose diet (HFHSD) are widely used to model diet-induced obesity, yet whether they similarly impact on metabolic and cardiovascular regulation remains unclear. Here, we compared metabolic, sympathetic and cardiovascular responses to HFD and HFHSD in male C57BL/6J mice, using normal chow diet (NCD) as a control. Five weeks old mice were fed NCD, HFD, or HFHSD for 16 weeks. Both diets induced similar weight gain (28±1 g vs. 12±1 g in NCD), adiposity, glucose intolerance, and insulin resistance. Telemetry recordings showed elevated blood pressure in HFD and HFHSD mice compared with NCD, with no differences between the diets. Heart rate was similarly increased in both groups. Despite comparable metabolic and BP effects, diet-specific patterns of sympathetic activation emerged: renal SNA was greater in HFD, whereas lumbar SNA was higher in HFHSD; splanchnic SNA increased similarly in both. iDISCO-mediated imaging of renal tyrosine hydroxylase revealed a significant increase in sympathetic innervation of the kidney in HFHSD mice relative to lean controls. Baroreflex sensitivity was reduced in both diet groups. Echocardiography demonstrated increased cardiac mass, ventricular wall thickness, and left atrial size in HFHSD-fed mice, with higher cardiac output uniquely in HFHSD. Vascular studies revealed impaired endothelium-dependent vasodilation in both diets, while endothelium-independent vasodilation was selectively impaired in HFHSD. These findings demonstrate that both HFD and HFHSD elevate blood pressure, enhance sympathetic outflow, blunt baroreflex function, and promote cardiovascular remodeling, while HFHSD elicits distinct neural and vascular signatures. Together, these results highlight the diverse cardiovascular consequences of Western dietary patterns. 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.

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