Gut microbiota is crucial for function of the gastrointestinal (GI) tract, and modulates the communication between the GI tract and the central nervous system. Microbial metabolites such as propionate have been shown to regulate blood pressure (BP), while butyrate, one of the major bacterial fermented byproducts, reportedly produces beneficial effects in multiple dysbiosis-related diseases. We previously showed that chronic supplementation with soluble fiber-rich, butyrolytic diet modified microbiota and increased BP in the spontaneously hypertensive rat (SHR). Here, we tested the impact of same diet on BP regulation in the Wistar Kyoto rats (WKY). Methods: Male 4 weeks old WKY were placed on either the fructooligosaccharides/inulin-rich diet (fiber, N=6), or its calorie-matched control diet (control, N=6) (Research Diets, Inc.) for 14 weeks. Baseline BP was measured by tail cuff every week for the duration of the study, and by telemetry at the end of the study and during 20 minutes of restraint stress. Spectral analysis of BP waveform was performed during restraint stress to measure autonomic variables. Results: We observed no significant difference in mean BP measured by tailcuff or by telemetry between the two groups. However, there was an increase in mean BP after 2 minutes of restraint (104.5 ± 7.45 mmHg vs. 116.3 ± 3.19 mmHg; p=0.0411, n=6), which was associated with a trend in increase in LF/HF variable linked with vasovagal balance (1.99 ± 1.43 vs. 3.04 ± 1.46, p=0.17) in the fiber group when submitted to restraint stress. Conclusion: Unlike in the SHR, fiber-rich diet did not alter baseline BP in the normotensive WKY. However, chronic fiber diet produced autonomic imbalance and increased BP in response to restraint stress in the WKY.

The main function of Leptin is to inform the individual's nutritional status to hypothalamus, which in turn regulate food intake and energy expenditure. Such actions are orchestrated by phosphorylation of ObRb receptor on tyrosine 985 and 1138, the latter is related to metabolism and Stat3 pathway. Recently, it was demonstrated that high serum levels of leptin, which is seen in DIO, correlates strongly with hypertension. On the other hand, obese individuals have resistance to metabolic actions of leptin (satiety and thermogenesis). To investigate the molecular hypothalamic pathways that characterize the selective activity of leptin on the effect of blood pressure (BP) increase, adults Sprague Dawley rats were fed with standard diet (SD) or HFD for three months and were submitted to chronic ICV injection of leptin (2μg/day) or saline (2μl) for 10 days. BP, food intake and energy expenditure were assessed before and after treatment. SD+leptin group had reduced food intake from 109,48±8,48 to 57,3±7,04 kcal / day, increased energy expenditure from 85,6±1,87 to 94,4±0,58 kcal/day/kg^0,75 and consequently weight reduction of 15,25±3,54 g (P <0.001 all) which did not occur in HFD+leptin. However, both SD and HFD group, leptin increased BP of 10.44±0.12% (from 103,7±0,7 to 114,8±0,8 mmHg) and 14.22±1.9% (from 118,6±1,3 to 132,2±1,5 mmHg), respectively. As expected, obese animals had elevated levels of serum leptin when compared to SD group (SD: 2,24±0,38 ng/dl and HFD: 9,88±1,82 ng/dl, p<0,05). Additionally, we evaluate the main activated signal pathways by leptin in hypothalamus. SD+leptin group showed a significant increase in activity of Stat3, Akt and in MAPK expression. However, HFD+leptin group manifested an increase only on the expression of MAPK pathway. Both SD and HFD leptin-treated groups had higher ObRb tyr985 phosphorylation, which was not observed with the pObRb tyr1138. It was possible to see that ObRb tyr985 dependent pathway is responsive to leptin in SD and HFD, and ObRb tyr1138 as well as the related protein Stat3 and Akt are reduced in obese animals. Therefore, it may be suggested that in HFD-induced obesity hypothalamic pathway ObRb tyr985 / MAPK, unlike the other pathways, is not resistent and can be related to cardiovascular actions of leptin.