Abstract
Recently, it has been argued that obesity leads to a chronic pro-inflammatory state that can accelerate immunosenescence, predisposing to the early acquisition of an immune risk profile and health problems related to immunity in adulthood. In this sense, the present study aimed to verify, in circulating leukocytes, the gene expression of markers related to early immunosenescence associated with obesity and its possible relationships with the physical fitness in obese adults with type 2 diabetes or without associated comorbidities. The sample consisted of middle-aged obese individuals (body mass index (BMI) between 30-35 kg/m²) with type 2 diabetes mellitus (OBD; n = 17) or without associated comorbidity (OB; n = 18), and a control group of eutrophic healthy individuals (BMI: 20 - 25 kg/m²) of same ages (E; n = 18). All groups (OBD, OB and E) performed the functional analyses [muscle strength (1RM) and cardiorespiratory fitness (VO2max)], anthropometry, body composition (Air Displacement Plethysmograph), blood collections for biochemical (anti-CMV) and molecular (gene expression of leptin, IL-2, IL-4, IL-6, IL-10, TNF-α, PD-1, P16ink4a, CCR7, CD28 and CD27) analyses of markers related to immunosenescence. Increased gene expression of leptin, IL-2, IL-4, IL-10, TNF-α, PD-1, P16ink4a, CCR7 and CD27 was found for the OBD and OB groups compared to the E group. Moreover, VO2max for the OBD and OB groups was significantly lower compared to E. In conclusion, obesity, regardless of associated disease, induces increased gene expression of markers associated with inflammation and immunosenescence in circulating leukocytes in obese middle-aged individuals compared to a eutrophic group of the same age. Additionally, increased adipose tissue and markers of chronic inflammation and immunosenescence were associated to impairments in the cardiorespiratory capacity of obese middle-aged individuals.
Highlights
Obesity is considered a global health problem, affecting a large part of the population and becoming one of the main causes of reduced quality of life, morbidity and mortality [1,2,3]
Several studies have proposed that the central mechanism underlying obesity and its related comorbidities comes from a persistent state of low-grade chronic inflammation together with dysregulation in the inflammation-stress feedback mechanisms [4,5,6], mainly due to increased production of pro-inflammatory markers such as leptin, interleukin-6 (IL-6), tumor necrosis factor -a (TNF-a), C-reactive protein (CRP) and monocyte chemotactic protein - 1 (MCP1) in the withe adipose tissue, together with the M1 macrophage phenotype infiltration in this tissue associated with obesity [6,7,8]
In animal models used in experimentation, Hunsche et al [5] observed that macrophage and lymphocyte chemotaxis, macrophage phagocytosis, NK cell activity, lymphocyte proliferative response, secretion of IL-1b, TNF-a, IL-6, IL-2 and IL- 10 in leukocyte cultures, as well as the antioxidant and oxidative capacity of obese adult rats were significantly impaired when compared to non-obese adult rats and similar to elderly rats, concluding that obesity can generate premature immunosenescence that is aggravated as the obese adult rat ages
Summary
Obesity is considered a global health problem, affecting a large part of the population and becoming one of the main causes of reduced quality of life, morbidity and mortality [1,2,3]. Cell damage was seen to appear when these levels were increased (as in the case of obesity) and innate immunity cells, such as macrophages, exhibit an over-activated production of oxidative and inflammatory compounds which occurs mainly in the absence of antigenic stimulus and cannot be neutralized by antioxidant nor anti-inflammatory defenses, leading to a chronic state of oxidative and inflammatory stress [5, 10]. Given the context of neuro-immune-endocrine communication and its changes in oxidative and inflammatory situations, as well as the impairment of the immune system, characteristics similar to those observed in aging, it has been speculated that obesity generates premature immunosenescence (biological aging of the immune system), and this may be one of the reasons for the increased rate of morbidity and risk of death related to this disease [12,13,14,15]
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