Background: Adiponectin has vascular protective actions and is bound by T-cadherin. Results: T-cadherin-deficient mice lack skeletal muscle tissue-resident adiponectin and display impaired revascularization that is not improved by treatment with exogenous adiponectin. Conclusion: Expression of T-cadherin is critical for revascularization actions of adiponectin in vitro and in vivo.Significance: The T-cadherin/adiponectin interaction is important for vascular homeostasis.

Background: Adiponectin has vascular and metabolic protective actions; however, its in vivo receptor-mediated signaling pathways are incompletely understood. Results: Adiponectin receptor 1 (AdipoR1)-deficiency exacerbates diet-induced metabolic dysfunction, and AdipoR2 deficiency results in impaired revascularization.

Over the past two decades, adiponectin has been studied in more than eleven thousand publications. A classical adipokine, adiponectin was among the first factors secreted from adipose tissue that were found to promote metabolic function. Circulating levels of adiponectin consistently decline with increasing body mass index. Clinical and basic science studies have identified adiponectin’s cardiovascular-protective actions, providing a mechanistic link to the increased incidence of cardiovascular disease in obese individuals. While progress has been made in identifying receptors essential for the metabolic actions of adiponectin (AdipoR1 and AdipoR2), few studies have examined the receptor-mediated signaling pathways in cardiovascular tissues. T-cadherin, a GPI-anchored adiponectin-binding protein, was recently identified as critical for the cardiac-protective and revascularization actions of adiponectin. Adiponectin is abundantly present on the surfaces of vascular and muscle tissues through a direct interaction with T-cadherin. Consistent with this observation, adiponectin is absent from T-cadherin-deficient tissues. Since T-cadherin lacks an intracellular domain, additional studies would further our understanding of this signaling pathway. Here, we review the diverse cardiometabolic actions of adiponectin.

BackgroundThe idiopathic inflammatory myopathies represent a group of autoimmune diseases that are characterized by lymphocyte infiltration of muscle and muscle weakness. Insulin-like 6 (Insl6) is a poorly characterized member of the insulin-like/relaxin family of secreted proteins, whose expression is upregulated upon acute muscle injury.MethodsIn this study, we employed Insl6 gain or loss of function mice to investigate the role of Insl6 in a T cell-mediated model of experimental autoimmune myositis (EAM). EAM models in rodents have involved immunization with human myosin-binding protein C with complete Freund’s adjuvant (CFA) emulsions and pertussis toxin.ResultsInsl6-deficiency in mice led to a worsened myositis phenotype including increased infiltration of CD4 and CD8 T cells and the elevated expression of inflammatory cytokines. Insl6-deficient mice show significant motor function impairment when tested with treadmill or Rotarod devices. Conversely, muscle-specific overexpression of Insl6 protected against the development of myositis as indicated by reduced lymphocyte infiltration in muscle, diminished inflammatory cytokine expression and improved motor function. The improvement in myositis by Insl6 could also be demonstrated by acute hydrodynamic delivery of a plasmid encoding murine Insl6. In cultured cells, Insl6 inhibits Jurkat cell proliferation and activation in response to phytohemagglutinin/phorbol 12-myristate 13-acetate stimulation. Insl6 transcript expression in muscle was reduced in a cohort of dermatomyositis and polymyositis patients.ConclusionsThese data suggest that Insl6 may have utility for the treatment of myositis, a condition for which few treatment options exist.