Pulmonary Circulation in Obesity, Diabetes, and Metabolic Syndrome

Obesity, diabetes mellitus, and the metabolic syndrome are important risk factors for the development of cardiovascular disease, with significant impact on human morbidity and mortality. Several decades of research have accumulated considerable knowledge about the mechanisms by which metabolic conditions precipitate systemic cardiovascular diseases. In short, these mechanisms are thought to involve changes in the external environment of vascular cells, which are mediated by the pro-inflammatory effects of adipokines, free fatty acids, and hyperglycemia. Thus, it has been hypothesized that the pulmonary circulation, witnessing similar insults as the systemic circulation, may be equally vulnerable to the development of vascular disease. Accordingly, recent attention has focused on exploring the mechanistic and epidemiological relationships among obesity, type 2 diabetes mellitus, metabolic syndrome, and pulmonary vascular diseases. In this article, we discuss in detail the preclinical evidence showing a modest but perceivable impact of metabolic disorders on the pulmonary circulation. In addition, we review the existing epidemiological studies examining the relationship among cardiovascular risk factors and pulmonary vascular diseases, using the acute respiratory distress syndrome and pulmonary arterial hypertension as examples. We conclude by discussing areas of limitations in the field and by suggesting future directions for investigation, including the notion that the pulmonary circulation may, in fact, be a resilient entity in the setting of some metabolic perturbations. © 2020 American Physiological Society. Compr Physiol 10:297-316, 2020.