CD8+ T cells in beige adipogenesis and energy homeostasis.

Although accumulation of lymphocytes in the white adipose tissue (WAT) in obesity is linked to insulin resistance, it remains unclear whether lymphocytes also participate in the regulation of energy homeostasis in the WAT. Here, we demonstrate enhanced energy dissipation in Rag1-/- mice, increased catecholaminergic input to subcutaneous WAT, and significant beige adipogenesis. Adoptive transfer experiments demonstrated that CD8+ T cell deficiency accounts for the enhanced beige adipogenesis in Rag1-/- mice. Consistently, we identified that CD8-/- mice also presented with enhanced beige adipogenesis. The inhibitory effect of CD8+ T cells on beige adipogenesis was reversed by blockade of IFN-γ. All together, our findings identify an effect of CD8+ T cells in regulating energy dissipation in lean WAT, mediated by IFN-γ modulation of the abundance of resident immune cells and of local catecholaminergic activity. Our results provide a plausible explanation for the clinical signs of metabolic dysfunction in diseases characterized by altered CD8+ T cell abundance and suggest targeting of CD8+ T cells as a promising therapeutic approach for obesity and other diseases with altered energy homeostasis.

CRH Receptor Signalling: Potential Roles in Pathophysiology.

To maintain homeostatic equilibrium, living organisms have evolved complex adaptation systems that control an array of behavioural, autonomic, neuroendocrine and immune responses. One of the important switches of this system is the hypothalamic hormone corticotropin-releasing hormone (CRH), which together with a family of related peptides (urocortins, UCNs) orchestrate stress-coping responses that reinstate homeostasis. Persistent disturbances in the homeostatic equilibrium either due to inadequate or persistently uncontrolled responses have been associated with pathogenic mechanisms of disease. CRH and UCNs exert their actions by activating two receptors of the Class B1 GPCRs, CRH-R1 and CRH-R2. Their signalling versatility allows activation of multiple and diverse signalling pathways characterized by 'cell-specific agonist-dependent signalling' responses. Alternative mRNA splicing, interactions with intracellular protein partners and mechanisms that allow selective regulation of signalling potency and termination, provide additional levels of regulation to fine-tune cellular responses. Although understanding of CRH-R signalling is still incomplete, recent important advances in decoding CRH-R structure and signalling properties uncovered key important functions and roles in physiology and pathobiology.