Obesity is a major health issue in developed as well as developing countries. While obesity is associated with relatively good health status in some individuals, it may become a health issue for others. Obesity in the context of inflammation has been studied extensively. However, whether obesity in its various forms has the same adverse effects is a matter of debate and requires further research. During its natural history, metabolically healthy obesity (MHO) converts into metabolically unhealthy obesity (MUHO). What causes this transition to occur and what is the role of obesity-related mediators of inflammation during this transition is discussed in this paper. 1. Background Obesity and its associated comorbidities have become major health problems in the world [1]. The association between obesity and the development of major complications in acute pancreatitis [2], fatty liver diseases [3], vascular inflammation and coronary heart disease [4, 5], chronic obstructive pulmonary disease [6], risk of cerebral ischemia and brain injury [7], atherosclerotic vascular disease and myocardial infarction [8], and cancers [9–11] are strongly linked to chronic inflammation (Figure 1). In particular, insulin resistance, a direct or indirect result of obesity, is characterized by a chronic state of subclinical inflammation [12] and inactivation of a number of inflammatory mediators [13–15]. Elevated serum concentrations of C-reactive protein [16], interleukin IL-6, IL-8, and tumor necrosis factor (TNF)-α are observed in obese individuals with elevated insulin resistance [17]. Figure 1: The relationship between obesity and comorbidities. The consequences of obesity are depicted and include the immunological component (T cells and macrophages) that drives inflammation together with adipocytes. The associated pathologies mentioned have been associated with increased levels of inflammatory markers that are also increased in obesity. Although it is not clear which one is the consequence and which one is the cause both are associated to higher clinical vulnerability. MIP-1 α: macrophage inflammatory protein-1 alpha; MCP-1: monocyte chemotactic protein-1; IP-10: interferon gamma-induced protein 10; SAA: serum amyloid A; Th1: T helper 1 cytokine; COPD: chronic obstructive pulmonary disease. Interestingly, however, a life course perspective on obesity recognizes that obese individuals are not a homogeneous group, but highly heterogeneous, given individual differences in terms of health status and functional ability among obese individuals. A substantially large number of
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