Background: Visceral adipose tissue (VAT) is one of the most important sources of proinflammatory molecules in obese people and it conditions the appearance of insulin resistance and diabetes. Thus, understanding the synergies between adipocytes and VAT-resident immune cells is essential for the treatment of insulin resistance and diabetes.Methods: We collected information available on databases and specialized literature to construct regulatory networks of VAT resident cells, such as adipocytes, CD4+ T lymphocytes and macrophages. These networks were used to build stochastic models based on Markov chains to visualize phenotypic changes on VAT resident cells under several physiological contexts, including obesity and diabetes mellitus.Results: Stochastic models showed that in lean people, insulin produces inflammation in adipocytes as a homeostatic mechanism to downregulate glucose intake. However, when the VAT tolerance to inflammation is exceeded, adipocytes lose insulin sensitivity according to severity of the inflammatory condition. Molecularly, insulin resistance is initiated by inflammatory pathways and sustained by intracellular ceramide signaling. Furthermore, our data show that insulin resistance potentiates the effector response of immune cells, which suggests its role in the mechanism of nutrient redirection. Finally, our models show that insulin resistance cannot be inhibited by anti-inflammatory therapies alone.Conclusion: Insulin resistance controls adipocyte glucose intake under homeostatic conditions. However, metabolic alterations such as obesity, enhances insulin resistance in adipocytes, redirecting nutrients to immune cells, permanently sustaining local inflammation in the VAT.

The function and morphology of β-cells is largely dependent on insulin demand. As β-cells cover a bigger cell proportion in pancreas islets, changes of insulin producer cells affect the whole pancreatic islet morphology. Growth factors as the neurotrophins regulate the pancreas physiology, besides; physical exercise increases insulin sensitivity, and further modifies brain derived neurotrophic factor (BDNF) concentration in plasma. The aim of this study was to investigate the effects of chronic exercise (running in a treadmill for 8 weeks) intensity on pancreatic islet morphometry in healthy state. The BDNF receptor effect on the pancreatic islet morphometry was also evaluated. Adult male Wistar rats were divided in 6 groups: Control (C); moderate intensity training (MIT); high intensity training (HIT) did not treat with BDNF receptor inhibitor (K252a), and C, MIT and HIT treated with K252a. The results shown that chronic exercise induces β-cells hypertrophy without BDNF receptor participation. On the other hand, the moderate exercise increases the number of β cells per islet; the last effect does not require TrkB participation. In sedentary conditions, the K252a treatment reduced the β-cell density. Exercise intensity has differential effects on pancreas islet morphometry in healthy model; furthermore, BDNF receptor plays a role to maintain the amount of β-cells in sedentary state.

Objective: This study aimed to examine the effects of moderate (MIT) and high-intensity training (HIT) chronic exercise on plasma tumor necrosis factor alpha (TNF-alpha) level and its impact on Langerhans islet morphology in healthy rats. Methods: Two-month old normal male Wistar rats were divided into three groups: control (C, n= 6), MIT (n= 6), and HIT (n= 4). The training protocol consisted in 24 sessions of running on a treadmill at 60-80% maximal oxygen consumption (VO2max) for MIT, and >80% VO2max for HIT. TNF-alpha and insulin were measured with ELISA tests. Duodenal pancreas was dissected to analyze the Langerhans islets by immunohistochemistry, a correlation analysis was performed with the nuclei/total islet area. Results: HIT and MIT rats showed lower TNF-alpha plasma levels than controls. Plasma insulin level decreased significantly in HIT compared with C and MIT. In addition, the islet area and nuclei density per islet were higher in the exercise groups compared with C. However, none of the groups showed PD1 immunoreactivity. Conclusions: Under healthy conditions, the chronic exercise reduced plasmatic TNF-alpha level, and in the same sense, increased the size of the Langerhans islets, depending to the exercise intensity.

Background and objectives: Adipose tissue and skeletal muscle secrete adiponectin, a hormone abundantly secreted by adipocytes, that through the adiponectin receptor, regulate glucose and lipid metabolism. Adiponectin appears to protect skeletal muscles from inflammatory damage induced by oxidative stress. It has been suggested that decreased adiponectin levels could be associated with pathologic conditions, including obesity and diabetes. Furthermore, some studies suggest that exercise could have a beneficial effect by increasing adiponectin levels, but this observation remains controversial. It is also unknown if physical exercise modifies adiponectin expression in skeletal muscles. The aim of this study was to investigate the effect of chronic exercise on serum adiponectin and adiponectin expression in slow-twitch (soleus) and fast-twitch (plantaris) muscles in healthy rats. Materials and methods: Two-month-old male Wistar rats were randomly divided into three groups with n = 6 in each group: control (C), moderate-intensity training (MIT), and high-intensity training (HIT). The rats were conditioned to run on a treadmill for the 8-week period. Forty-eight hours after the last session, blood samples were collected for adiponectin measurements and total RNA was isolated from plantaris and soleus muscles to measure by RT-qPCR adiponectin receptor 1 and adiponectin mRNA expression level. Results: MIT and HIT groups had reduced adiponectin protein levels in serum and the plantaris muscle, but not changes in adiponectin protein were observed in the soleus muscle. No significant differences in Adiponectin receptor 1 (AdipoR1) gene expression were observed following intense or moderate exercise in either muscle group studied. Conclusions: Our study shows that decreasing levels of circulating adiponectin is a result of physical exercise and should not be generalized as a predictive marker of disease.

CD4⁺ T lymphocytes have been classified into several lineages, according to their gene expression profiles and their effector responses. Interestingly, recent evidence is showing that many lineages could yield hybrid phenotypes with unique properties and functions. It has been reported that such hybrid lineages might underlie pathologies or may function as effector cells with protection capacities against molecular threats. In this work, we reviewed the characteristics of the hybrid lineages reported in the literature, in order to identify the expression profiles that characterize them and the markers that could be used to identify them. We also review the differentiation cues that elicit their hybrid origin and what is known about their physiological roles.