Figure 4.

Proposed mechanisms of obesity- and autophagy-related pathogenesis of lung disease. (A) Obesity induces the production of inflammatory cytokines such as IL-1β by macrophages in the adipose or lung tissue, leading to the production of IL-17. IL-17 has been correlated with worsening lung inflammation and injury in diseases such as asthma and fibrosis. Autophagy can sequester pro–IL-1β, decreasing IL-1β production and thus negatively regulating IL-17 levels. (B) Obesity is characterized by NLRP3 inflammasome activation that increases the production of inflammatory cytokines such as IL-1β and IL-18, which has been shown to contribute to lung disease pathogenesis. Autophagy can inhibit inflammasome activation, thereby decreasing IL-1β and IL-18 production. (C) Adipocytes are characterized by adipokine production such as leptin and adiponectin. Under obesity conditions, leptin levels are increased as a result of leptin resistance. Leptin has systemic effects and can increase the production of inflammatory cytokines. Adiponectin is decreased in obesity. Adiponectin has antiinflammatory properties through increasing production of IL-10 and inhibits the production of proinflammatory cytokines such as TNF-α, IL-1β, IL-1RA, IL-R2, IL-6, and IL-17. ALI, acute lung injury; COPD, chronic obstructive pulmonary disease; NLRP3, nod-like receptor protein-3.