A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis

作者：Reilly Shannon M; Ahmadian Maryam; Zamarron Brian F; Chang Louise; Uhm Maeran; Poirier BreAnne; Peng Xiaoling; Krause Danielle M; Korytnaya Evgenia; Neidert Adam; Liddle Christopher; Yu Ruth T; Lumeng Carey N; Oral Elif A; Downes Michael; Evans Ronald M; Saltiel Alan R^*

来源：Nature Communications, 2015, 6(1): 6047.

DOI：10.1038/ncomms7047

The search for effective treatments for obesity and its comorbidities is of prime importance. We previously identified IKK-epsilon and TBK1 as promising therapeutic targets for the treatment of obesity and associated insulin resistance. Here we show that acute inhibition of IKK-epsilon 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.

• 出版日期2015-1