Figure 2.

Thrombospondin-1 (TSP1) impinges adversely on metabolic pathways and endocrine systems. TSP1 is upregulated by hypoxia, inflammation, hyperglycemia, high-fat intake, and age. Through activation of CD47 signaling, TSP1 adversely potentiates metabolic disease and diabetes via effects on mitochondrial homeostasis, metabolism, and survival in adipocytes and pancreatic islets. TSP1 signaling mediated by CD47 on vascular cells modulates angiogenesis and blood flow, and on macrophages and T cells modulates innate and adaptive immunity. CD47 interacting with signal regulatory protein-α (SIRPα) or SIRPγ further regulates innate and T cell immunity to impact metabolic disease.