Paracrine cross-talk between skeletal muscle and macrophages in exercise by PGC-1α-controlled BNP

Activation of resident and infiltrating immune cells is a central event in training adaptation and other contexts of skeletal muscle repair and regeneration. A precise orchestration of inflammatory events in muscle fibers and immune cells is required after recurrent contraction-relaxation cycles. However, the mechanistic aspects of this important regulation remain largely unknown. We now demonstrate that besides a dominant role in controlling cellular metabolism, the peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha) also has a profound effect on cytokine expression in muscle tissue. Muscle PGC-1 alpha expression results in activation of tissue-resident macrophages, at least in part mediated by PGC-1 alpha-dependent B-type natriuretic peptide (BNP) production and secretion. Positive effects of exercise in metabolic diseases and other pathologies associated with chronic inflammation could accordingly involve the PGC-1 alpha-BNP axis and thereby provide novel targets for therapeutic approaches.