Background: Heart failure with preserved ejection fraction (HFpEF) is the most common cause of heart failure, and is characterized by impaired diastolic relaxation. Bariatric surgery significantly improves diastolic relaxation, but a mechanism beyond weight loss remains unknown. Objective: We tested the hypothesis that a sleeve gastrectomy (SG) will improve diastolic dysfunction independent of weight loss due to post-operative alterations in the entero-cardiac axis. Setting: University Research laboratory. Methods: Male, Wistar rats were fed a high-fat diet (HFD) or low-fat diet (LFD) for 10 weeks followed by SG-HFD, pair-fed sham HFD, ad-lib sham HFD, or ad-lib sham LFD (n=9-14 per group). At least 2 months postoperatively, cardiac function, meal tolerance, glucose tolerance, and cardiac gene expression were compared between groups. Results: Only the SG cohort showed significant improvements in post-operative diastolic relaxation (isovolumetric relaxation time pre: 14.7 ± 2.3 msec, post: 11.2 ± 1.8 msec, p<0.001). SG significantly increased active glucagon-like peptide-1 (p=0.03). Compared to pair-fed sham HFD rats, SG-HFD rats had significantly altered mRNA cardiac gene expression including sarco/ endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) (p<0.001).

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