[Contractive function of mesenteric lymph nodes in obese rats].

Abstract

Over the past 50 years, the prevalence of obesity around the world has increased several times and has become a pandemic. The effect of obesity on the lymphatic system, which plays a key role in the regulation of fluid homeostasis, immune cell migration, antigen presentation, and resolution of inflammatory responses, is poorly understood, and there is no data on the contractile activity of the lymph nodes in obesity. The purpose of the research was to investigate the parameters and mechanisms of dysfunction of the contractile function of the mesenteric lymph nodes of rats in obesity caused by the feeding with the high-fat diet (HFD). Material and methods. The study was conducted on 50 male Sprague-Dawley rats. Rats aged 6 weeks were randomly divided into groups: a control group (n=10) fed a standard diet and a group of rats (n=40) kept on HFD (60% fat content by calorie value). Rats received food and water ad libitum for 16 weeks. Before the end of the experiment, four groups of HFD rats were formed: obesity resistant animals (HFD-OR, n=11), without additional interventions (HFD, n=10), rats which were administered dexamethasone three days before the study (HFD+Dexa, n=9), HFD followed by 8-week diet restriction (HFD+DR, n=9). At the end of the experiment, mesenteric lymph nodes (LNs) were taken from rats under anesthesia and their contractile function was studied in a myograph using 1400W, dynastat and Tempol. Results. LNs of control rats had a high level of tone and generated spontaneous high-amplitude phasic contractions. The LNs of HFD rats had a low initial tone, and rare low-amplitude phasic contractions were recorded in them. The parameters of contractile activity of the LNs of rats in HFD-OR and HFD+Dexa groups differed slightly from the corresponding parameters of the LNs of rats in the control group. Calorie restriction for 8 weeks in obese rats (HFD+DR) resulted in an increase in tone, frequency and amplitude of phasic contractions of the LNs compared to those in HFD rats. iNOS inhibition caused a significant increase in the tone, amplitude and frequency of phasic contractions of the LNs in the HFD group. An increase in the frequency of phasic contractions was observed only in the LNs of HFD+Dex and HFD+DR rats. Inhibition of cyclooxygenase 2 did not affect the contractile function of the LNs of rats of all groups, with the exception of animals from the HFD group (increase in the amplitude and frequency of phasic contractions). Tempol significantly increased the tone, frequency and amplitude of phasic contractions of the LNs in rats of the HFD group and increased the frequency of phasic contractions of the LNs of the HFD+DR rats. Conclusion. A high-fat diet leads to impaired contractile function of rat LNs and can create additional obstacles to the movement of lymph, promoting its leakage into surrounding tissues. Obesity is accompanied by the development of inflammation in the LNs and perinodal adipose tissue, which induces the expression of inducible NO synthase, cyclooxygenase-2 and the accumulation of reactive oxygen species (ROS). NO, prostaglandins and ROS have an inhibitory effect on the SMC capsules of the LNs, leading to a decrease in tonic tension and a weakening of spontaneous phasic contractions. The reason for inhibition of LN contractile function is obesity, but not consumption of food high in fat. Transferring obese rats to a calorie-restricted diet results in a decrease in body weight and visceral fat mass and an improvement in LN contractile function.