Significance Women with polycystic ovary syndrome (PCOS) have reduced fertility and increased risk of developing type 2 diabetes. Adiponectin, an adipocyte-derived hormone, together with adipocyte size, is the strongest factor associated with insulin resistance in PCOS. The potential causal relationship among adiponectin levels, infertility, and metabolic dysfunction in PCOS is, however, unknown. Exploiting mouse models, we found that adiponectin is indeed involved in PCOS-related insulin resistance, and, albeit to a much smaller extent, is also involved in the development of reproductive dysfunction. Thus, increased levels of adiponectin can prevent prepubertal androgen-induced metabolic dysfunction in dihydrotestosterone-exposed mice with PCOS-like traits. Collectively, our findings support the notion that altered adipose tissue functionality is a key mediator of metabolic dysfunction in women with PCOS.