A nutrient-responsive AMPK/TBK1 circuit restricts adipocyte catabolism.
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| Formato: | Artículo científico |
| Lenguaje: | en |
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JCI insight
2026
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| author | Wisessaowapak, Churaibhon Skorobogatko, Yuliya Kim, Hyeonhui Feng, Xue Son, Seunghwan Fu, Haipeng Zhang, Sitao Lertvilai, Pichaya Chang, Lina Hoang, Annie Chen, Hetty Bedsted, Sarah Valentine, Joseph Huh, Jin Young Zhao, Peng Reilly, Shannon M Watcharasit, Piyajit Ahmadian, Maryam Saltiel, Alan R |
| author_facet | Wisessaowapak, Churaibhon Skorobogatko, Yuliya Kim, Hyeonhui Feng, Xue Son, Seunghwan Fu, Haipeng Zhang, Sitao Lertvilai, Pichaya Chang, Lina Hoang, Annie Chen, Hetty Bedsted, Sarah Valentine, Joseph Huh, Jin Young Zhao, Peng Reilly, Shannon M Watcharasit, Piyajit Ahmadian, Maryam Saltiel, Alan R Wisessaowapak, Churaibhon Skorobogatko, Yuliya Kim, Hyeonhui Feng, Xue Son, Seunghwan Fu, Haipeng Zhang, Sitao Lertvilai, Pichaya Chang, Lina Hoang, Annie Chen, Hetty Bedsted, Sarah Valentine, Joseph Huh, Jin Young Zhao, Peng Reilly, Shannon M Watcharasit, Piyajit Ahmadian, Maryam Saltiel, Alan R |
| collection | PubMed - marine biology |
| contents | A nutrient-responsive AMPK/TBK1 circuit restricts adipocyte catabolism. Wisessaowapak, Churaibhon Skorobogatko, Yuliya Kim, Hyeonhui Feng, Xue Son, Seunghwan Fu, Haipeng Zhang, Sitao Lertvilai, Pichaya Chang, Lina Hoang, Annie Chen, Hetty Bedsted, Sarah Valentine, Joseph Huh, Jin Young Zhao, Peng Reilly, Shannon M Watcharasit, Piyajit Ahmadian, Maryam Saltiel, Alan R Animals Protein Serine-Threonine Kinases Mice AMP-Activated Protein Kinases Adipocytes Obesity Male Energy Metabolism Signal Transduction Mice, Inbred C57BL Aminoimidazole Carboxamide Fasting Insulin Resistance Mice, Knockout Aminopyridines Ribonucleotides Metabolic adaptation to both caloric excess and restriction promotes energy conservation by suppressing catabolic pathways via feedback mechanisms that remain incompletely defined. We identified TANK binding kinase 1 (TBK1) as a nutrient- and inflammation-responsive brake on AMPK signaling in adipocytes. Fasting or pharmacological AMPK activation induced Tbk1 transcription via a PGC1α/nuclear respiratory factor 1 axis, which, in turn, limited AMPK activity through a phosphorylation cascade to conserve energy. In obesity, this AMPK/TBK1 axis was disrupted due to chronically elevated basal TBK1, thereby restricting energy expenditure during fasting. Adipocyte-specific TBK1 deletion enhanced fasting-induced AMPK activation, mitochondrial function, and lipolytic gene expression in both lean and obese mice. Pharmacological TBK1 inhibition with amlexanox recapitulated these effects. Combined treatment of mice with amlexanox and the AMPK activator AICAR enhanced weight loss, improved glucose tolerance and insulin sensitivity, and suppressed inflammatory and lipogenic programs in adipose tissue, as well as fibrotic gene expression in the liver. Building on prior clinical observations linking TBK1 inhibition to metabolic health, these findings defined a nutrient-sensitive AMPK/TBK1 feedback loop that limited adipocyte catabolism and suggested that dual targeting of TBK1 and AMPK may help counteract metabolic adaptation and enhance the durability of obesity therapies. |
| format | Artículo científico |
| id | pubmed_42100877 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | JCI insight |
| record_format | pubmed |
| spellingShingle | A nutrient-responsive AMPK/TBK1 circuit restricts adipocyte catabolism. Wisessaowapak, Churaibhon Skorobogatko, Yuliya Kim, Hyeonhui Feng, Xue Son, Seunghwan Fu, Haipeng Zhang, Sitao Lertvilai, Pichaya Chang, Lina Hoang, Annie Chen, Hetty Bedsted, Sarah Valentine, Joseph Huh, Jin Young Zhao, Peng Reilly, Shannon M Watcharasit, Piyajit Ahmadian, Maryam Saltiel, Alan R Animals Protein Serine-Threonine Kinases Mice AMP-Activated Protein Kinases Adipocytes Obesity Male Energy Metabolism Signal Transduction Mice, Inbred C57BL Aminoimidazole Carboxamide Fasting Insulin Resistance Mice, Knockout Aminopyridines Ribonucleotides A nutrient-responsive AMPK/TBK1 circuit restricts adipocyte catabolism. Wisessaowapak, Churaibhon Skorobogatko, Yuliya Kim, Hyeonhui Feng, Xue Son, Seunghwan Fu, Haipeng Zhang, Sitao Lertvilai, Pichaya Chang, Lina Hoang, Annie Chen, Hetty Bedsted, Sarah Valentine, Joseph Huh, Jin Young Zhao, Peng Reilly, Shannon M Watcharasit, Piyajit Ahmadian, Maryam Saltiel, Alan R Animals Protein Serine-Threonine Kinases Mice AMP-Activated Protein Kinases Adipocytes Obesity Male Energy Metabolism Signal Transduction Mice, Inbred C57BL Aminoimidazole Carboxamide Fasting Insulin Resistance Mice, Knockout Aminopyridines Ribonucleotides Metabolic adaptation to both caloric excess and restriction promotes energy conservation by suppressing catabolic pathways via feedback mechanisms that remain incompletely defined. We identified TANK binding kinase 1 (TBK1) as a nutrient- and inflammation-responsive brake on AMPK signaling in adipocytes. Fasting or pharmacological AMPK activation induced Tbk1 transcription via a PGC1α/nuclear respiratory factor 1 axis, which, in turn, limited AMPK activity through a phosphorylation cascade to conserve energy. In obesity, this AMPK/TBK1 axis was disrupted due to chronically elevated basal TBK1, thereby restricting energy expenditure during fasting. Adipocyte-specific TBK1 deletion enhanced fasting-induced AMPK activation, mitochondrial function, and lipolytic gene expression in both lean and obese mice. Pharmacological TBK1 inhibition with amlexanox recapitulated these effects. Combined treatment of mice with amlexanox and the AMPK activator AICAR enhanced weight loss, improved glucose tolerance and insulin sensitivity, and suppressed inflammatory and lipogenic programs in adipose tissue, as well as fibrotic gene expression in the liver. Building on prior clinical observations linking TBK1 inhibition to metabolic health, these findings defined a nutrient-sensitive AMPK/TBK1 feedback loop that limited adipocyte catabolism and suggested that dual targeting of TBK1 and AMPK may help counteract metabolic adaptation and enhance the durability of obesity therapies. |
| title | A nutrient-responsive AMPK/TBK1 circuit restricts adipocyte catabolism. |
| topic | Animals Protein Serine-Threonine Kinases Mice AMP-Activated Protein Kinases Adipocytes Obesity Male Energy Metabolism Signal Transduction Mice, Inbred C57BL Aminoimidazole Carboxamide Fasting Insulin Resistance Mice, Knockout Aminopyridines Ribonucleotides |
| url | https://pubmed.ncbi.nlm.nih.gov/42100877/ |