A subcutaneous adipose tissue–liver signalling axis controls hepatic gluconeogenesis
In: Nature Communications, Jg. 6 (2015), Heft 1
academicJournal
- 6047
Zugriff:
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.
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A subcutaneous adipose tissue–liver signalling axis controls hepatic gluconeogenesis
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Autor/in / Beteiligte Person: | Reilly, Shannon M ; Ahmadian, Maryam ; Zamarron, Brian F ; Chang, Louise ; Uhm, Maeran ; Poirier, Bre ; Anne ; 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 |
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Zeitschrift: | Nature Communications, Jg. 6 (2015), Heft 1 |
Veröffentlichung: | eScholarship, University of California, 2015 |
Medientyp: | academicJournal |
Umfang: | 6047 |
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