Diet-induced obesity triggers the infiltration of immune cells into adipose tissue, leading to inflammation and promoting the development of type 2 diabetes. Adipose tissue is an active endocrine organ that secretes hormones and cytokines (known as adipokines when derived from adipose tissue), which mainly have pro-inflammatory functions. However, Ouchi et al. now report that secreted frizzled-related protein 5 (Sfrp5) is a newly identified anti-inflammatory adipokine. Sfrp5 expression and secretion were reduced in rodent models of obesity and type 2 diabetes, and Sfrp5-deficient mice exhibited classical markers of metabolic dysfunction, such as elevated fasting glucose and insulin levels, increased liver triglycerides, reduced glucose clearance, and increased insulin resistance and adipose tissue macrophage infiltration. Conversely, Sfrp5 treatment reversed metabolic dysfunction in several mouse models of obesity. The researchers propose that Sfrp5 neutralises Wnt5a-mediated noncanonical JNK1 activation, a key pathway that regulates adipose tissue inflammation and glucose metabolism, in both adipocytes and macrophages. These findings identify Sfrp5 as an anti-inflammatory adipokine that could be targeted in therapies for obesity-induced type 2 diabetes.