Does inflammation determine whether obesity is metabolically healthy or unhealthy? The aging perspective

Abstract

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.

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-1α: 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.

Figure 2

Differences between metabolically healthy and unhealthy obesity and similarities with aging. The hallmarks of metabolically healthy obesity are depicted and associate poorly with comorbidities while metabolically unhealthy obesity shares similarities with the aging process and are both associated with increased prevalence to pathologies and chronic conditions. BMI: body mass index; CVD: cardiovascular diseases.

Figure 3

Conversion of naïve LDL to oxidized LDL and formation of foam cells from monocytes: implication of aging and obesity in sustaining/worsening inflammation. A typical example of how chronic condition can participate in the development of diseases. In this case, atherosclerotic plaque formation is increased by parallel proinflammatory signals derived from obesity and/or inflammaging. LDL: low-density lipoprotein; ROS: reactive oxygen species; CMV: cytomegalovirus; RANTES: regulated and normal T cell expressed and secreted.