The prevalence of obesity and type 2 diabetes is a major health burden. Insulin resistance is the primary metabolic disorder driving the development of diabetes and is central to many cardiometabolic disorders. The modulation of insulin sensitivity in the body is the result of complex nutrient and hormone interactions. Adipose tissue is an endocrine organ that secretes a plethora of factors, called adipokines, into the systemic circulation. Leptin and adiponectin are well-studied adipokines that act via central and peripheral mechanisms to promote insulin sensitivity. Although leptin has a complex systemic role in the body, chronic leptin treatment may be clinically relevant in type 1 diabetes and lipodystrophic conditions to help steady glucose homeostasis. More recently, adipolin has been described as an insulin-sensitising protein secreted from adipose tissue. We have identified adipolin as a target gene of Krüppel-like factor 3 (Klf3), and have shown that loss of Klf3 in mice results in upregulation of adipolin associated with improvements in glucose tolerance. The known actions of these insulin-sensitising adipokines suggest that they confer a healthy metabolic phenotype when effectively acting in the body. Research on adipolin is in its infancy and there remains much work to be done to overcome leptin and adiponectin resistance in the overweight and obese population.