The goal of this exploratory study was to develop and assess a prediction model which can potentially be used as a biomarker of breast cancer, based on anthropometric data and parameters which can be gathered in routine blood analysis. For each of the 166 participants several clinical features were observed or measured, including age, BMI, Glucose, Insulin, HOMA, Leptin, Adiponectin, Resistin and MCP-1. Machine learning algorithms (logistic regression, random forests, support vector machines) were implemented taking in as predictors different numbers of variables. The resulting models were assessed with a Monte Carlo Cross-Validation approach to determine 95% confidence intervals for the sensitivity, specificity and AUC of the models. Support vector machines models using Glucose, Resistin, Age and BMI as predictors allowed predicting the presence of breast cancer in women with sensitivity ranging between 82 and 88% and specificity ranging between 85 and 90%. The 95% confidence interval for the AUC was [0.87, 0.91]. These findings provide promising evidence that models combining age, BMI and metabolic parameters may be a powerful tool for a cheap and effective biomarker of breast cancer.

BACKGROUND AND PURPOSE: The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been fully elucidated. This study was designed to assess the effect of metformin on impaired endothelial function, oxidative stress, inflammation and advanced glycation end products formation in type 2 diabetes mellitus.EXPERIMENTAL APPROACH: Goto‐Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes, fed with normal and high‐fat diet during 4 months were treated with metformin for 4 weeks before evaluation. Systemic oxidative stress, endothelial function, insulin resistance, nitric oxide (NO) bioavailability, glycation and vascular oxidative stress were determined in the aortic rings of the different groups. A pro‐inflammatory biomarker the chemokine CCL2 (monocyte chemoattractant protein‐1) was also evaluated.KEY RESULTS: High‐fat fed GK rats with hyperlipidaemia showed increased vascular and systemic oxidative stress and impaired endothelial‐dependent vasodilatation. Metformin treatment significantly improved glycation, oxidative stress, CCL2 levels, NO bioavailability and insulin resistance and normalized endothelial function in aorta.CONCLUSION AND IMPLICATIONS: Metformin restores endothelial function and significantly improves NO bioavailability, glycation and oxidative stress in normal and high‐fat fed GK rats. This supports the concept of the central role of metformin as a first‐line therapeutic to treat diabetic patients in order to protect against endothelial dysfunction associated with type 2 diabetes mellitus.

Recently, compelling evidence points to dysbiosis and disruption of the epithelial intestinal barrier as major players in the pathophysiology of metabolic disorders, such as obesity. Upon the intestinal barrier disruption, components from bacterial metabolism and bacteria itself can reach peripheral tissues through circulation. This has been associated with the low-grade inflammation that characterizes obesity and other metabolic diseases. While circulating bacterial DNA has been postulated as a common feature of obesity and even type 2 diabetes, almost no focus has been given to the existence and effects of bacteria in peripheral tissues, namely the adipose tissue. As a symbiont population, it is expected that gut microbiota modulate the immunometabolism of the host, thus influencing energy balance mechanisms and inflammation. Gut inflammatory signals cause direct deleterious inflammatory responses in adipose tissue and may also affect key gut neuroendocrine mechanisms governing nutrient sensing and energy balance, like incretins and ghrelin, which play a role in the gut-brain-adipose tissue axis. Thus, it is of major importance to disclose how gut microbiota and derived signals modulate neuroendocrine and inflammatory pathways, which contribute to the dysfunction of adipose tissue and to the metabolic sequelae of obesity and related disorders. This review summarizes the current knowledge regarding these topics and identifies new perspectives in this field of research, highlighting new pathways toward the reduction of the inflammatory burden of metabolic diseases.

Myokines are peptides produced and secreted by the skeletal muscle, with autocrine, paracrine, and endocrine actions. Many of them are overexpressed during physical exercise and appear to contribute to the benefits of exercise to metabolic homeostasis. Irisin, resulting from the cleavage of the membrane protein FNDC5, was shown to induce adipocyte browning, with increased lipid oxidation and thermogenesis. Myonectin was only recently discovered and initial studies revealed a role in fatty acid uptake and oxidation in adipose tissue and liver. However, the mechanisms of their regulation by exercise are not entirely established. Impaired secretion and action of myokines, such as irisin and myonectin, may have a role in the establishment of insulin resistance. On the other hand, several studies have shown that insulin resistance in the skeletal muscle may change myokines expression and secretion. This may have consequences on lipid and glucose metabolism in adipose tissue and lead to a vicious cycle between impaired myokines production and insulin resistance. This review summarizes the current knowledge about the influence of skeletal muscle insulin resistance on the secretion of irisin and myonectin, as well as its impact on adipose tissue metabolism.