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Changes in the conservation cell make obesity and diabetes more susceptible to infections

Publicado em 20 março 2019

Disturbing people with type 2 diabetes are more likely to develop infectious diseases because both conditions affect the immune system. The immune system of these patients did not know the method that was known now.

Research published in the University of Biomedical Science at São Paulo University (ICB-USP) and research published in the Journal of Scientific Reports suggests that this phenomenon is associated with changes in neutrophils, the first defense cells to respond to the aggression agent.

This work is the result of a biochemist Wilson Mitsuro, a doctoral project of Tatagiba Kuuvara, which supports the hypothesis under the guidance of biological Tatiana's Carolina Alba-Lorerón. This research was done at the former laboratory of Professor Rui Curie at ICB-USP, currently at Instituto Butananton and Cruzeiro do Sul University.

"There is very good consistency in this work because it shows that the state of insulin resistance, which we call metabolic syndrome, is associated with a significant change in neutrophils. It suggests that this change may be related to infectious processes in the case of obese and type 2 diabetes. "Curie said.

Kuvabara says that so far he does not know why obesity and diabetes are more vulnerable to the destruction of infectious diseases. "We found an answer by investigating neutrophils, when it comes to TLR 4 protein, it recognizes LPS poison. [lipopolissacarídeo, principal componente da membrana externa de bactérias gram-negativas] Invasive pathogenic organisms, "he said.

Toll-like receptors (TLR) are a family of proteins that are part of the immune system. TLR 4 losses in the activation process are associated with the lower capacity of the defense cells to fight the asteroid.

"TLR4 is a rare receptor, that is, it is present in the outer art of most of the body cells, but its main role is in the cells of the immune system." Defense said, "Quwabara said.

TLR 4 activation occurs when this receptor is found in LPS of Gram-negative bacteria. Identify toxins – which include chlamydia, Brucellosis, salmonellosis, meningitis, cholera, syphilis and buobonic plague. On the invader's belief, the signal is sent to the immune system, which increases the production of inflammatory substances.

Experimental models

To understand what happens with the activation of TLR 4 in obese and diabetic type 2 topics, Quwabara experimented with two different models: with a goose-kacuzzi rats and other extinction rats.

The Goto-Kakazaki lineage was selected in Japan for the study of diabetes in 1970. These animals naturally exhibit all the classic features of type 2 diabetes, such as insulin resistance, fasting hyperglycemia, hyperinsulinia, and plasma triglycerides and cholesterol levels. ITB-USP Rats were imported specifically for the experiment and were the only representatives of Goto-Kakizaki strain in Brazil.

The second model was created with a viper, which was a common descendant used in laboratories, which was given high fat diet for eight weeks. The third control group of the vista rats received a standard ration and no weight gain was found. At least eight animals were used in each experiment model.

After eight weeks of fat diet, vista rats show symptoms of obesity, such as accumulation of liver fats, glucose intolerance, increase in white adipose tissues, insulin resistance and inflammation.

LPS To evaluate the neutrophil response, the intra-tracheal implantation of LPS was performed in obesity mice and type 2 diabetes models. A cannula was placed in the traces of rats and with syringe, the solution was LPS. Was entered directly with. In the lungs.

After six hours, LPS Rats were sacrificed for the evaluation of the immune system response of the institute. At that time, blood samples were collected from each animal, as well as bronchoclovilor ligazes to collect neutrophil cells from the inflammatory environment.

Neutrophil counts, cytokines and chemoes (proteins that promote inflammation) and milioporoxidase enzyme activity (MPO, responsible for generating reactive reactionary oxygen species to remove pathogens) were used in bronco allevelar language materials of different groups).

It was found that the intraretreal implantation of LPS encourages the migration of neutrophils to the lungs. The number of these conservation cells collected in the Bronco Elvalver Lave was less than the control group in obese rats and the Got-Kakizaki rats. Likewise, Got-Kakazaki rats and obese rats show lower MPA activity compared to the control group.

"After the LPS stimulation, the neutrophils collected from Goto-Kakazaki rats were found to be less efficient. Nutrophils show more deaths in the blood of goose-kagazaki rats compared to the control group, which is represented by the loss of integrity. Cell and enzyme increased Content that triggers cell death [caspase-3 clivada]"Kuvabara said.

"With regard to obese rats, we found that even though they were still in blood, their neutrophils were more susceptible to cell death, so before migrating to the lungs to fight inflammation caused by LPS Instruction," he said.

According to the researcher, the data show that the neoprophils of Goto-Kakazaki and obese groups are LPS. Had a restless response, that is, they were LPS To be tolerant Kuvabara said that this tolerance can be an explanation for the higher mortality rates in obese and diabetic individuals as a result of bacterial infection.

Biochemical ratio

According to Professor Curie, work is important because they show neutrophils in rats and diabetic rats, while they can not react effectively when they come in contact with bacteria. "How is the infection process set up in this way," he said.

TLR4 is an essential receptor for congenital immune response and loss of its activation capacity causes the inflammatory process to be compromised.

"Now we know biochemical reasons why diseases in obese and diabetic patients are likely to occur." "More research is needed to explain why TRL4 Cam is inactive in this research." Curie said.

Research published in Scientific Reports is part of the Thematic Project "Influence of Cellular and Atomic Mechanism and Lean and Goose-Kakazaki Skin Rats Insulin Resistance: Causes and Organizations with Diet and Exercise" and "Risks with Skeleton Muscle Hypotropy Type 1 Diabetes Mellitus," by Q Both integration and backed by FAPESP.

Kuvabara is currently a postdoctoral ally at ICB-USP under the guidance of Professor Jose Sipola NATO and PhapeseF Fellows.

This article Obesity and type 2 diabetes mellitus mice induce lipopolysychide tolerance in neutrophils. (Doi: https://doi.org/10.1038/s41598-018-35809-2), Wilson Mitsuos Tatagiba Quwabara, Caroline Naomi Fukusawa Yokota, Rui Curie and Tatiana's Carolina Alba-Laurezo, published on www.nature.com Is there. / Article / s 41598-018-35809-2.