Growing evidence supports the hypothesis of a positive feedback loop between type 1 innate lymphoid cells (including NK cells) and Mφ in people with a positive energy balance (30, 45–47). Adipocyte hypertrophy, fibrosis, hypoxia, and cell death cause release of inflammatory molecules, which stimulate adipose tissue Mφ (48). Stressed adipocytes express NKp46 ligands that directly stimulate NK cells and probably other type 1 innate lymphoid cells (47). In response to the inflammatory molecules, Mφ produce IL-12 and IL-15, which stimulate NK cells and other type 1innate lymphoid cells to produce IFN-γ, TNFα, and IL-6 (30, 45). These products, in turn, stimulate Mφ, setting up a positive feedback loop. Inflammatory cytokines, including IL-6 and TNFα, which affect skeletal muscle, the vasculature, and other tissues, cause pathologies associated with frailty and the metabolic syndrome (48, 49). Our data fit into this picture (Figure 7B). We found that IL-15 is elevated in relation to human VAT mass. Plasma C-reactive protein, a measure of inflammation, correlated strongly with plasma IL-15 (data not shown). We propose that IL-15 stimulates NK cells, both in a local paracrine fashion in VAT and in an endocrine fashion (Figure 7B). To explain the negative correlation between IL-15 and muscle strength, we propose that IL-15 itself and other inflammatory factors inhibit skeletal muscle (Figure 7B).