Metabolic Functions of G Protein-Coupled Receptors and ß-Arrestin-Mediated Signaling Pathways in the Pathophysiology of Type 2 Diabetes and Obesity.

Seven transmembrane receptors (7TMRs), often termed G protein-coupled receptors (GPCRs), are the most common target of therapeutic drugs used today. Many studies suggest that distinct members of the GPCR superfamily represent potential targets for the treatment of various metabolic disorders including obesity and type 2 diabetes (T2D). GPCRs typically activate different classes of heterotrimeric G proteins, which can be subgrouped into four major functional types: Gαs, Gαi, Gαq/11, and G12/13, in response to agonist binding. Accumulating evidence suggests that GPCRs can also initiate ß-arrestin-dependent, G protein-independent signaling. Thus, the physiological outcome of activating a certain GPCR in a particular tissue may also be modulated by ß-arrestin-dependent, but G protein-independent signaling pathways. In this review, we will focus on the role of G protein- and ß-arrestin-dependent signaling pathways in the development of obesity and T2D-related metabolic disorders.

Doxorubicin modulated clock genes and cytokines in macrophages extracted from tumor-bearing mice.

Circadian rhythm is essential for cellular regulation of physiological, metabolic, and immune functions. Perturbations of circadian rhythms have been correlated with increased susceptibility to cancer and poor prognosis in the cancer treatment. Our aim is to investigate the role of doxorubicin (DOX) treatment on clock genes expression and inflammation in intraperitoneal macrophages and the antitumoral response. METHODS: Macrophages were extracted from intraperitoneal cavity of mice without or with Lewis lung carcinoma (LLC) and treated with DOX totaling four groups (CTL, LLC, LLC+DOX and DOX) and analyzes of clock genes in six time points (ZT02, ZT06, ZT10, ZT14, ZT18 AND ZT22). Intraperitoneal macrophages cell culture was stimulated with LPS and DOX and clock genes and inflammatory profile were analyzed. In tumor were analyzed macrophages markers. RESULTS: The expression of F4/80 (ZT22) and CD11c (ZT06) tumor tissue was significantly differed between LLC and LCC+DOX groups. In the intraperitoneal macrophages, DOX increased Clock (ZT10), Rev-Erbα (ZT18 and ZT22) and Per2 expressions (ZT18); in the LLC+DOX group was increased Bmal1 (ZT10), Per2 (ZT18) and NF-kB (ZT22) expressions; IL-6 expression increased in the LCC group (ZT02). In intraperitoneal macrophages cell culture stimulated with DOX and LPS after 24 h decreased Clock and Per1. DOX causes depression after 6 and 24 h in TNF-α content and Per2 gene expression after 24 h IL-1ß expression was reduced also. CONCLUSION: DOX treatment in vivo disrupted cytokine and clock genes expression in intraperitoneal macrophages suppressing immune response. Moreover, macrophages cultured with DOX had decreased expression of LPS-stimulated inflammatory cytokines.

Aerobic Exercise Modulates the Free Fatty Acids and Inflammatory Response During Obesity and Cancer Cachexia.

White adipose tissue (WAT) is no longer considered a tissue whose main function is the storage of TAG. Since the discovery of leptin in 1994, several studies have elucidated the important role of WAT as an endocrine organ, the source of the adipokines. The low-grade inflammation observed in obese and cancer cachexia patients is explained, at least partially, by the exacerbated release of proinflammatory adipokines. Despite of the recent progress in the characterization of the various adipokines and lipokines produced by WAT, little is known about the mechanisms regulating the secretion of these molecules in different physiological and pathological circumstances. Chronic exercise is a nonpharmacological therapy employed in several chronic diseases and shows an anti-inflammatory effect through the regulation of the cytokine network. In this review, we address the potential mechanisms by which the aerobic physical exercise modulate the production and release of inflammatory adipokines, as well as the inflammation-lipolysis axis in WAT, with special focus in the therapeutic role of exercise in obesity-associated insulin resistance and cancer cachexia.

Brazilian Jiu-Jitsu Simulated Competition Part II: Physical Performance, Time-Motion, Technical-Tactical Analyses, and Perceptual Responses.

The aim of this study was to analyze performance, time structure, technical actions, and perceptual responses in Brazilian jiu-jitsu athletes during a simulated competition. For this purpose, 10 athletes were analyzed in a simulated competition (4 matches of 10 minutes). Physical tests and scales of the perception of effort and recovery were applied. The matches were recorded for the purpose of technical-tactical analysis and to determine the time structure. The main results show that in the simulated competition, reaction time (F(2.5,17.6) = 2.7; p = 0.087; η² = 0.28) and flexibility (F(7,63) = 1.5; p = 0.172; η² = 0.15) were unchanged across the matches. An analysis of variance showed a significant difference for grip endurance using the kimono (F(2.0,15.9) = 8.1; p = 0.004; η² = 0.50), which was not confirmed by the Bonferroni test. Jump height indicated postactivation potentiation after match 2 (F(7,63) = 3.5; p = 0.003; η² = 0.28). The maximal isometric handgrip strength in the dominant hand (F(3.2,28.6) = 2.9; p = 0.049; η² = 0.24) and in the nondominant hand (F(7,63) = 3.8; p = 0.002; η² = 0.30) showed a decline after matches 3 and 4. Although these data indicate the onset of fatigue, the effort/pause ratio of the matches was not altered (F(3,12) = 0.6; p = 0.624; η² = 0.13). The perceptions of effort (F(3,27) = 0.9; p = 0.469; η² = 0.09) and recovery (F(1.9,17.0) = 2.4; p = 0.125; η² = 0.21) and the degree of fatigue reported (F(1.5,13.8) = 0.5; p = 0.588; η² = 0.05) did not change during the simulated competition. Thus, it may be concluded that the execution of successive matches causes a decline in maximal isometric handgrip strength. No changes in the time structure of the matches or in the perceptual responses were observed.