Overweight – An Invisible Social Pattern That Promotes Obesity-Related Chronic Inflammatory Diseases Potentiated By “Immuno-Aging”

Overweight and obesity, to a greater degree, are conditions characterized by abnormal or excessive fat accumulation that impair health and bring about psychosocial and economic difficulties. They are considered risk factors for a number of diseases, such as cardiovascular, musculoskeletal, type 2 diabetes mellitus, and some types of cancers [1, 2]. In 2016, more than one-third of adults worldwide were classified as obese or overweight, both in developed and developing countries. Of note, most of the world’s population lives in countries where overweight and obesity kill more people than being underweight [3].

The world’s population is also aging increasingly over the years. Globally, the population aged 60 or over is growing faster than all younger age groups, and it is expected that the number of older persons will double by 2050 and more than triple by 2100 [4]. Aging, often called senescence, is a natural process characterized by a gradual decline in body functions due to multiple organ dysfunctions. Collectively, these data indicate that the combination of excessive weight and aging may confer greater risks of diseases and death.

The immune system is considered the most protective system of the body, as it keeps the organisms free of invaders, either internal or external. It regulates the inflammatory response, a reaction of cells/tissues after infection or injury, which is characterized by redness, heat, swelling, pain, and loss of function [5]. The immune system is intrinsically connected with other systems, such as the endocrine (composed by glands that produce hormones that regulate the metabolism, growth, and development) and neurological (a complex network of cells and messengers that record and distribute information from the brain and spinal cord to various part of the body) systems.

Therefore, immune dysfunctions have great potential to be deleterious [6]. Both excessive weight and aging are associated with marked changes in the immune system, leading to a state of chronic low-grade inflammation [7, 8]. Obese, overweight, and old individuals are more susceptible to viral, bacterial, and fungal infections [1]. The links between excessive adipose (fat) tissue accumulation and aging, along with the observation that adults with excessive weight are prematurely aged individuals, led the field researchers to postulate the term “adipaging” [9].

Cytokines are bioactive molecules produced by many different cells (e.g. in the blood and adipose tissue) that coordinate local and systemic inflammatory responses and other biological processes. As their levels are altered in different inflammatory diseases, there is enormous clinical interest in the quantification of cytokines in body samples like blood and urine as biological markers, or “biomarkers,” of disease severity, progression, or response to treatments. Obesity/overweight and senescence share alterations in the body levels of several cytokines [10]. Despite extensive research over the past decades, our understanding of the role of cytokines in obesity/overweight and aging remains limited.

Considering the promising use of cytokines as biomarkers of chronic diseases associated with excessive weight and senescence and the link between these processes, we investigated the levels of three soluble cytokines in the blood (interleukine-17/IL-17, chemokine CXCL-16, and the bone morphogenetic protein-2/BMP-2) in middle-aged women and elderly women with overweight and obesity. We correlated these data with anthropometric parameters of the studied women, which assess the size, shape, and proportions of the human body. This study was published in the Immunity & Ageing journal in 2017 [11].

According to our data, the blood levels of CXCL-16, IL-17, and BMP-2 were higher in all obese and most of the overweight women when compared to normal weight women, independently of age. Obese women tended to have increased levels of these cytokines than overweight women. However, we observed that the focus of medical attention must start with overweight individuals because, in terms of the production of inflammatory mediators, they are very similar to the obese ones. In other words, we cannot neglect the overweight because this condition is “in an inflammatory speaking” similar to that condition (obesity) associated with different comorbidities. In our society, sometimes being overweight is partially accepted and living among us using an invisible mask. When produced in excess, CXCL-16 and IL-17 might contribute to the development of atherosclerosis, a disease of the arteries characterized by the deposition of plaques of fatty material on their inner walls that lead to cardiovascular diseases [12, 13].

BMP-2 is a potent inducer of bone formation, but it is also associated with various adverse events when in excess, for example, induction of inflammation [14]. Therefore, the overproduction of these cytokines might predispose the development of chronic diseases in the future. In addition, these cytokines were correlated in a positive manner with anthropometric parameters, especially in the elderly. This means that women who have increased CXCL-6, IL-17, and BMP-2 levels also have higher body measurements associated with fat accumulation in this period of life. It is worth noting that obese and overweight women in middle age had similar levels of IL-17 and BMP-2 as elderly women with normal weight, suggesting that having excessive weight in adult life resembles these cytokines’ profiles in senescence.

The present study provides complementary information about IL-17, CXCL-16, and BMP-2, and their potential as soluble biomarkers related to excessive weight in middle-aged and elderly women. However, they need to be further investigated by population studies that follow overweight and obese individuals as they get older. These studies will confirm if cytokines, like those measured in our study, could be useful in the preventive management of chronic inflammatory diseases associated with excessive weight and aging.

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