(P04-044-24) Sulforaphane Prevents High-Fat Diet-Induced Cardiometabolic Dysfunction and Muscle Atrophy

Objectives: Sulforaphane (SFN) is found in many cruciferous vegetables like broccoli, cabbage, cauliflower and kale and has been shown to improve cardiometabolic function. In the current study, we integrate transcriptome studies of the muscle and adipose tissues with numerous physiological assessments of vascular and metabolic functions to better understand the potential protective mechanisms of SFN against high-fat diet-induced cardiometabolic disease.

Methods: C57BL Mice (6 M and 6 F) were divided into two groups (1) HFD (60% fat) plus s.c. injection of SFN (0.5 mg/kg/day) for 15 weeks (2) HFD plus s.c. injection of vehicle (control). Pre and post-intervention measurements included body weight and composition (via NMR), metabolic function and physical activity (metabolic cages), food consumption (BIODAQ system), OGTT test, forelimb grip strength, blood pressure (BP; CODA system), heart function (Echocardiogram), and flow-induced dilation (FID) in mesenteric arterioles. Finally, RNA seq in skeletal muscle and fat was performed.

Results: SFN effectively reduced body weight, maintained muscle mass, and improved glucose tolerance and muscle strength. The SFN group showed increased activity and energy expenditure and improved diurnal rhythms in food intake and whole-body respiratory exchange ratio (RER) compared to controls. SFN also showed lower BP and higher arteriolar FID indicative of improved vasoreactivity. SFN preserved the cardiac systolic and diastolic function (ejection fraction and E/A ratio) and contractility (longitudinal strain) levels that were impaired in controls. RNA seq of muscle showed activation of the PPARα/RXRα, insulin, mTOR, and endothelial nitric oxide synthase (eNOS) signaling pathways, and inhibition of muscle atrophy and mitochondrial dysfunction pathways in the SFN mice. Similarly RNA seq of fat showed significant changes in adipogenesis, inflammation, leptin signaling, fat browning, and wound healing pathways. Results were verified via mRNA assays. SFN-induced improvements were more significant in males than in females at the physiological and molecular levels.

Conclusions: SFN prevents HFD-related cardiometabolic dysregulations and enhances pathways related to muscle protein synthesis, mitochondrial function, endothelial function, and energy metabolism.

Funding Sources: R01 HL161386