Adipocyte Gs but not Gi signaling regulates whole-body glucose homeostasis.

•Chemogenetic stimulation of Gs signaling in adipose tissue potently induces hypoglycemia in mice.•The magnitude by which adipose Gs stimulation reduces blood glucose is similar to the hypoglycemic effects of insulin.•Chemogenetic stimulation of Gs signaling in adipose tissue ex vivo stimulates lipolysis.•Chemogenetic stimulation of adipose Gi signaling does not affect glycemia or lipolysis, but increases leptin levels.•Our data demonstrate the usefulness of chemogenetic technology to understand adipocytes functions.