The search for effective treatments for obesity and its comorbidities is of prime importance. We previously identified ​IKK-ε and ​TBK1 as promising therapeutic targets for the treatment of obesity and associated insulin resistance. Here we show that acute inhibition of ​IKK-ε and ​TBK1 with ​amlexanox treatment increases ​cAMP levels in subcutaneous adipose depots of obese mice, promoting the synthesis and secretion of the cytokine ​IL-6 from adipocytes and preadipocytes, but not from macrophages. ​IL-6, in turn, stimulates the phosphorylation of hepatic ​Stat3 to suppress expression of genes involved in gluconeogenesis, in the process improving ​glucose handling in obese mice.