Obesity, manifested by increased adiposity, represents a main cause of morbidity in the developed countries, causing increased risk of insulin resistance and type 2 diabetes mellitus. Recruitment of macrophages and activation of innate immunity represent the initial insult, which can be further exacerbated through secretion of chemokines and adipocytokines from activated macrophages and other cells within the adipose tissue. These events can impact adipogenesis, causing dysfunction of the adipose tissue and increased risk of insulin resistance. Various factors mediate adiposity and related insulin resistance including inflammatory and non-inflammatory factors such as pro and anti-inflammatory cytokines, adipokines and growth factors. In this review we will discuss the role of these factors in adipogenesis and development of insulin resistance and type 2 diabetes mellitus in the context of obesity. Understanding the molecular mechanisms that mediate adipogenesis and insulin resistance could help the development of novel therapeutic strategies for individuals at higher risk of insulin resistance and type 2 diabetes mellitus.

Background: Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. Methods: In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples. Results: Tumor necrosis factor-alpha (TNF-α) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-α were identified. The antioxidant catalase activity was positively correlated with levels of TNF-α. Telomere length increased significantly with sport intensity, especially in the younger group. Conclusion: HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted.

Background The global diabetes epidemic is largely attributed to obesity-triggered metabolic syndrome. However, the impact of insulin resistance (IR) prior to obesity on the high prevalence of diabetes and the molecular mediators remain largely unknown. This study aims to compare the metabolic profiling of apparently healthy lean/overweight participants with IR and insulin sensitivity (IS), and identify the metabolic pathways underlying IR. Methods In this cross-sectional study, clinical and metabolic data for 200 seemingly healthy young females (100 IR and 100 IS) was collected from Qatar Biobank. Orthogonal partial least square analysis was performed to assess the extent of separation between individuals from the two groups based on measured metabolites. Classical linear models were used to identify the metabolic signature of IR, followed by elastic-net-regularized generalized linear model (GLMNET) and Receiver Operating Characteristic (ROC) analysis to determine top metabolites associated with IR. Results Compared to lean/overweight participants with IS, those with IR showed increased androgenic steroids, including androsterone glucuronide, in addition to various microbiota byproducts, such as the phenylalanine-derivative carboxyethylphenylalanine. On the other hand, participant with IS had elevated levels of long chain fatty acids. A ROC analysis suggested a better discriminatory performance using 20 metabolites selected by GLMNET in comparison to the classical clinical traits (area under curve: 0.93 vs 0.73, respectively). Conclusion Our data confirm the multifactorial mechanism of IR with diverse spectrum of emerging potential biomarkers, including steroids, long chain fatty acids and microbiota metabolites. Further studies are warranted to validate these markers for diagnostic and therapeutic applications.

Objectives: Circulating cytokines and oxidative stress markers vary in response to different exercise regimens. This study aims to compare the immune-inflammatory and oxidative stress profiles of elite athletes from different sport disciplines as potential biomarkers of muscle damage, and cardiovascular demand. Methods: Serum samples from 88 consented elite male athletes from different sports disciplines (aquatics, n = 11, athletics, n = 22, cycling, n = 19, football, n = 28 and weightlifting, n = 8) collected at the anti-doping lab in Italy were screened for 38 cytokines and oxidative stress markers. Comparisons were made between different level of power, cardiovascular demand (CD) and endurance, as well as among the sport types. Results: The anti-inflammatory interleukin (IL)-10 was higher (p = 0.04) in moderate power compared with the high power group. Conversely, superoxide dismutase (SOD; p = 0.001) and malondialdehyde (MDA; p = 0.007) levels were greater in the higher power groups compared with the lower power counterpart. Among athletes who belong to different CD ranks, IL-1β and monocyte chemoattractant protein-1(MCP1) levels were higher (p = 0.03) in the low CD-rank group compared with high CD counterpart, whereas, SOD levels were higher (p = 0.001) in high and moderate CD-rank groups compared to low counterpart. For endurance groups, IL-10 and macrophage inflammatory protein (MIP)-1beta were increased (p = 0.03) in low/moderate endurance compared with the high endurance group. Finally, MIP1-beta, SOD and catalase varied significantly among the sports groups. Conclusion: Specific markers of inflammation and oxidative stress are associated with different sports disciplines and could be utilized as potential biomarkers of athletes' health, performance, and recovery from injury.

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