Thiago Bruder, Assistant Professor, Department of Pediatrics, Center for Pediatric Research in Obesity and Metabolism

Lipodystrophies and cardiovascular function

Adipose tissue is now recognized as a critical regulator of cardiovascular health, via the secretion of numerous bioactive products such as the adipokines, which present a wide range of endocrine and paracrine effects on the cardiovascular system. Several diseases lead to an alteration on the profile of adipose tissue in terms of expansion, body distribution and quality, triggering a dysregulated endocrine and/or paracrine functions. Active receptors for adipokines are broadly expressed in mammalian cells, including vascular and immune cells, which contribute to cardiovascular health and disease. 

We have used a mouse model of congenital lipodystrophy (Bscl2 deficient mouse) to elucidate the role of adipose tissue on cardiovascular and endocrine systems. Congenital lipodystrophy is a rare disease affecting very few people in the world and it is characterized by near or complete absence of adipose tissue. Our mouse model mimics very well the congenital lipodystrophy observed in humans showing a drastic reduction in adipose tissue and leptin plasma levels. Leptin is considered an adipokine, which has been extensively studied due its role on energy expenditure, satiety and metabolism, and is recently approved by FDA to treat metabolic abnormalities in congenital lipodystrophy. However, high levels of leptin have also been associated with sodium retention, increased sympathetic activity, elevated aldosterone production, cardiovascular damage and high blood pressure. 

Lately, we have shown that leptin replacement therapy improves some cardiovascular parameters in congenital lipodystrophy independent of changes on metabolic function. 

This seminar will focus on the cardiovascular changes such as vascular dysfunction, inflammation and remodeling associated with lipodystrophy and discuss the property of leptin replacement therapy to minimize the cardiovascular risk in this disease. In addition, we will discuss with more details our recent manuscript published in Hypertension, as well as present some new unpublished data.