Abstract
Experimental studies show that the unsaturated high-fat diet-induced obesity promotes vascular alterations characterized by improving the endothelial L-arginine/Nitric Oxide (NO) pathway. Leptin seems to be involved in this process, promoting vasodilation via increasing NO bioavailability. The aim of this study was to test the hypothesis that unsaturated high-fat diet-induced obesity does not generate endothelial dysfunction via increasing the vascular leptin/Akt/eNOS signaling. Thirty-day-old male Wistar rats were randomized into two groups: control (C) and obese (Ob). Group C was fed a standard diet, while group Ob was fed an unsaturated high-fat diet for 27 weeks. Adiposity, hormonal and biochemical parameters, and systolic blood pressure were observed. Concentration response curves were performed for leptin or acetylcholine in the presence or absence of Akt and NOS inhibitor. Our results showed that an unsaturated high-fat diet promoted a greater feed efficiency (FE), elevation of body weight and body fat (BF), and an adiposity index, characterizing a model of obesity. However, comorbidities frequently associated with experimental obesity were not visualized, such as glucose intolerance, dyslipidemia and hypertension. The evaluation of the endothelium-dependent relaxation with acetylcholine showed no differences between the C and Ob rats. After NOS inhibition, the response was completely abolished in the Ob group, but not in the C group. Furthermore, Akt inhibition completely blunted vascular relaxation in the C group, but not in the Ob group, which was more sensitive to leptin-induced vascular relaxation. L-NAME incubation abolished the relaxation in both groups at the same level. Although Akt inhibitor pre-incubation reduced the leptin response, group C was more sensitive to its effect. In conclusion, the high-unsaturated fat diet-induced obesity improved the vascular reactivity to leptin and does not generate endothelial dysfunction, possibly by the increase in the vascular sensitivity to leptin and increasing NO bioavailability. Moreover, our results suggest that the increase in NO production occurs through the increase in NOS activation by leptin and is partially mediated by the Akt pathway.
Highlights
Obesity, a disease characterized by excess body fat (BF), is recognized as a global epidemic since it affects virtually all age groups and social classes in both developed and developing countries (Suastika, 2006; Engin, 2017)
Obesity induced by a high-fat diet had a substantial elevation in adiposity parameters, feed efficiency (FE), LV, and LVW/tibia length when compared to C rats (Table 2)
There were no significant differences in comorbidities associated with obesity, since the Systolic Blood Pressure (SBP), TG, Cholesterol, LDL, high-density lipoprotein (HDL), and protein were similar between the groups (Table 3)
Summary
A disease characterized by excess body fat (BF), is recognized as a global epidemic since it affects virtually all age groups and social classes in both developed and developing countries (Suastika, 2006; Engin, 2017). Obese animal models induced by a high-energy diet (33% ground chow, 33% Nestle condensed milk, 7% sucrose, and 27% water) present impaired endothelium-dependent and independent relaxation in mesenteric arteries (Naderali et al, 2001). Fatani et al (2007) demonstrated that animals fed a high-saturated fat diet (45% fat) do not present any difference for vasoconstrictor responses to potassium chloride (KCl) or noradrenaline; the vascular relaxation in response to carbachol and sodium nitroprusside (SNP) is attenuated in mesenteric arteries, indicating that the highsaturated fat diet promotes vascular dysfunction. Other authors found no difference in acetylcholine-induced endothelium-dependent relaxation in the aorta of mice and obese rabbits induced by a high-fat diet with 58–60% of fat calories (Mundy et al, 2007; Bruder-Nascimento et al, 2017) or standard rabbit chow with 10% added fat (Jerez et al, 2012), which apparently is sex independent
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
