Obesity is considered to significantly increase the risk of the development of a vast range of metabolic diseases. However, adipogenesis is a complex physiological process, necessary to sequester lipids effectively to avoid lipotoxicity in other tissues, like the liver, heart, muscle, essential for maintaining metabolic homeostasis and has a crucial role as a component of the innate immune system, far beyond than only being an inert mass of energy storage. In pathophysiological conditions, adipogenesis promotes a pro-inflammatory state, angiogenesis and the release of adipokines, which become dangerous to health. It results in a hypoxic state, causing oxidative stress and the synthesis and release of harmful free fatty acids. In this review, we try to explain the mechanisms occurring at the breaking point, at which adipogenesis leads to an uncontrolled lipotoxicity. This review highlights the types of adipose tissue and their functions, their way of storing lipids until a critical point, which is associated with hypoxia, inflammation, insulin resistance as well as lipodystrophy and adipogenesis modulation by Krüppel-like factors and miRNAs.

In modern societies, high fructose intake from sugar-sweetened beverages has contributed to obesity development. In the diet, sucrose and high fructose corn syrup are the main sources of fructose and can be metabolized in the intestine and transported into the systemic circulation. The liver can metabolize around 70% of fructose intake, while the remaining is metabolized by other tissues. Several tissues including adipose tissue express the main fructose transporter GLUT5. In vivo, chronic fructose intake promotes white adipose tissue accumulation through activating adipogenesis. In vitro experiments have also demonstrated that fructose alone induces adipogenesis by several mechanisms, including (1) triglycerides and very-low-density lipoprotein (VLDL) production by fructose metabolism, (2) the stimulation of glucocorticoid activation by increasing 11β-HSD1 activity, and (3) the promotion of reactive oxygen species (ROS) production through uric acid, NOX and XOR expression, mTORC1 signaling and Ang II induction. Moreover, it has been observed that fructose induces adipogenesis through increased ACE2 expression, which promotes high Ang-(1-7) levels, and through the inhibition of the thermogenic program by regulating Sirt1 and UCP1. Finally, microRNAs may also be involved in regulating adipogenesis in high fructose intake conditions. In this paper, we propose further directions for research in fructose participation in adipogenesis.

Our findings suggest that curcumin might have therapeutic potential in treatment of heart disease in patients with established CKD by attenuating oxidative stress-related events as cardiac remodeling, mitochondrial dysfunction and cell death.

Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels.

The omentin is an adipokine, which role is due to the capacity of regulate metabolic (insulin sensitivity) and anti-inflammatory activities, thus conferring vascular protection during obesity and diabetes mellitus type 2. By this, it is important to know the mechanisms by which omentin confers cardiovascular protection, with the purpose of establish omentin a possible therapeutic target or molecule on this scenario.

Circulating microRNAs (miRNAs) and the functional implications of miRNAs contained in extracellular vesicles (EVs) have gained attention in the last decade. Little is known about the regulation of the abundance of plasma miRNAs in response to chronic ingestion of carbohydrates. Therefore, we explored the circulating levels of miR-21, miR-146a, miR-155, and miR-223 in rats consuming sucrose in drinking water. Weanling Wistar rats were 25 weeks with 30% sucrose in drinking water, and miRNAs expression was determined in total plasma and in microvesicles, by RT-qPCR with TaqMan probe based assays for miR-21, miR-146a, miR-155, and miR-223, using cel-miR-39 (as spike in control and reference). Endotoxemia was also measured. Sucrose-fed animals showed higher body weight and retroperitoneal adipose tissue as well as higher glucose and triglyceride plasma levels than controls. Plasma endotoxin levels were low and not different among groups. Plasma miR-21 and miR-223 were higher in the sucrose group (p < 0.05), whereas miR-155 tended to be lower (p = 0.0661), and miR-146a did not show significant differences. In the plasma EVs the same trend was found except for miR-146a that showed significantly higher levels (p < 0.05). Overall, our results show that high carbohydrate ingestion modulates circulating miRNAs levels related to an inflammatory response.

Metabolic syndrome (MS) may comprise several clinical conditions such as obesity, diabetes and inflammatory disorders, which are characterized by metabolic imbalances. The study of glucose transport and regulation by insulin in lymphocytes is important, since the way they increase inflammation and susceptibility to infections are common in MS. We studied glucose internalization in isolated thymocytes and splenocytes, its regulation by insulin, and the role of three glucose transporters (Gluts) in control and in MS rats. Control glucose internalization and insulin responses were lower in splenocytes than in thymocytes. Control and insulin-induced glucose internalization in thymocytes declined with age, while transport by splenocyte continued to respond to insulin. Control thymocyte glucose internalization was blocked by antibodies against Glut 1 and 4, while the insulin response also was blocked by an anti-Glut 3 antibody. On four month old control and insulin-induced response, splenocyte transport was only blocked by Glut 1 and 4 antibodies. At six months splenocyte glucose internalization depended on Glut 1 and was less sensitive to the effects of an anti-Glut 4 antibody. In MS splenocytes the capacity of anti-Glut 1 antibodies to inhibit control and insulin-dependent glucose transport was less significant, and we found that in MS rats, glucose internalization was dependent on Glut 3 and Glut 4. In summary, the altered metabolic state present in MS rats shows signs of modulation of glucose internalization by the Glut1, Glut 3 and Glut 4 transporters, compared with its own age control.

Background Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. MicroRNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-β signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction. Results Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated. Conclusions The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.