A Heart-Liver-Adipose Axis: the role of inter-organ crosstalk in cardiometabolic risk

Project: SFRN

Investigators

  • Ethan J J Anderson (PI)

Description

Obesity is a major risk factor for serious disorders such as type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), certain cancers and cardiovascular disease (CVD), the latter representing the leading cause of death in T2D patients. Only a fraction of obese individuals develop these disorders, however, suggesting that obesity alone is not sufficient for causality. Thus, elucidation of mechanisms underlying this heterogeneity among obese patients may unveil novel therapeutic targets for CVD prevention or treatment, and identify novel biomarkers of risk. The primary objective of this project is to uncover fundamental signaling pathways by which organ systems communicate through secretory factors in the circulation, and how disruption of these pathways leads to cardiometabolic disorders in obesity. Our research team has compelling preliminary evidence in support of several secreted factors which participate in a heart-liver-adipose crosstalk responsible for modulating cardiometabolic health. Consistent with the overall theme of our SFRN Center, the broad objective with this Basic Science project is to follow up on our exciting preliminary findings to elucidate the underlying mechanisms and physiological effects of this heart-liver-adipose axis, and how perturbation of this axis in obesity contributes to pathogenesis of related disorders such as T2D and CVD. Building on these proof-of-principle studies, we will leverage the novel candidates identified in the clinical and population studies to elucidate their mechanisms in these model systems. In addition, well use complementary approaches of metabolomics and profiling of circulating exosomes as proposed in the clinical and population studies, to determine if equivalent or similar processes develop in our mouse models of T2D and increased CVD risk. This approach will enable us to understand the interaction of these pathways either as mediators or as biomarkers of increased CVD risk in T2D.
Award amount$954,732.00
Award date01/01/2020
Program typeStrategically Focused Research Network
Award ID20SFRN35200003
Effective start/end date01/01/202012/31/2023
StatusActive