The role of astaxanthin in adipocyte biology

Abstract

Adipose tissues play a critical role in the regulation of systemic health. Astaxanthin (Ast), a natural antioxidant and anti-inflammatory compound, has been suggested to influence adipose tissue health. However, its role in regulation of proliferation of human adipose-derived stem cells (hASCs) and their differentiation into adipocytes is not well understood. This thesis examined how Ast affected hASC proliferation, adipogenic differentiation, and underlying signaling pathways. We found that Ast alone did not exhibit any effects on hASC proliferation or pro inflammatory signaling activities. However, Astaxanthin (Ast) blocked the actions of TNFα, a pro-inflammatory cytokine increased in obesity, thereby rescuing hASCs from its inhibition of proliferation and induction of proinflammatory signaling activity. At low doses (0.01 – 0.1 μM), Ast promoted adipogenesis in hASCs, indicated by upregulation of adipogenic protein markers and lipid accumulation. We showed that Ast enhanced adipogenesis through suppression of the anti-adipogenic Wnt/β-catenin signaling pathway, which led to the induction of key adipogenic transcription factors, C/EBPα and PPARγ. However, higher doses of Ast (2 – 10 μM) reduced adipogenesis and exhibited possible cytotoxicity. Our data demonstrated that physiologically achievable levels of Ast not only blocked TNFα-suppression of proliferation in hASCs but also enhanced their differentiation into adipocytes. These findings suggest that Ast may support hyperplastic growth of adipose tissues, which could ameliorate adipose tissue dysfunctions in obesity, providing protective effects against obesity-associated cardiometabolic disorders.