Citrus Essential Oil Nanoemulsions Mitigate Cardiac, Hepatic, and Pancreatic Injury in High-Fat Obese Rats via Adiponectin/SIRT1/Nrf2 Signaling Pathways.

Background: Methods: EOs were formulated as NEs using the ultrasonic emulsification method. The three NEs (150 mg/kg) were orally and separately administered along with the standard metformin (500 mg/kg) for 30 days after prior induction of obesity by HFD for a period of 12 weeks. Results: Treatments with NEs improved HFD-induced obesity with different potentials. The NE of CJO represented more cytoprotective and antisteatotic activities. It resulted in a preferential reduction of body weight and serum levels of glucose and lipids, as well as tissue injury and oxidative stress biomarkers that were accompanied by improved tissue architectures. At the molecular level, it upregulated the antioxidants Nrf2, HO-1, and SIRT1. It also increased the levels of adiponectin while decreasing visfatin. Furthermore, it downregulated the apoptotic executor, active caspase-3. Conclusions: The CJO NEs have shown strong promise in lowering obesity-induced hepatic steatosis and mitigating cardiac and pancreatic injury via hypoglycemic, antidyslipidemic, cytoprotective, antioxidant, and antiapoptotic activities. These beneficial effects are collectively associated with modulating the adiponectin/SIRT1/Nrf2 signaling cascade.