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A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis

Reilly, S.M., Ahmadian, M., Zamarron, B.F. et al.

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. Preliminary data in a small cohort of obese patients show a similar association. These data support an important role for a subcutaneous adipose tissue–liver axis in mediating the acute metabolic benefits of amlexanox on glucose metabolism, and point to a new therapeutic pathway for type 2 diabetes.

Citation

Reilly, S.M., Ahmadian, M., Zamarron, B.F. et al. "A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis" Nature Communications (2015): 6,047