| Autor: |
Hao Xie, Heier, Christoph, Xia Meng, Bakiri, Latifa, Pototschnig, Isabella, Zhiyuan Tang, Schauer, Silvia, Baumgartner, Vanessa J., Grabner, Gernot F., Schabbauer, Gernot, Wolinski, Heimo, Robertson, Graham R., Hoefler, Gerald, Wenwen Zeng, Wagner, Erwin F., Schweiger, Martina, Zechner, Rudolf |
| Předmět: |
|
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 3/1/2022, Vol. 119 Issue 9, p1-12, 24p |
| Abstrakt: |
Cancer-associated cachexia (CAC) is a hypermetabolic syndrome characterized by unintended weight loss due to the atrophy of adipose tissue and skeletal muscle. A phenotypic switch from white to beige adipocytes, a phenomenon called browning, accelerates CAC by increasing the dissipation of energy as heat. Addressing the mechanisms of white adipose tissue (WAT) browning in CAC, we now show that cachexigenic tumors activate type 2 immunity in cachectic WAT, generating a neuroprotective environment that increases peripheral sympathetic activity. Increased sympathetic activation, in turn, results in increased neuronal catecholamine synthesis and secretion, β-adrenergic activation of adipocytes, and induction of WAT browning. Two genetic mouse models validated this progression of events. 1) Interleukin-4 receptor deficiency impeded the alternative activation of macrophages, reduced sympathetic activity, and restrained WAT browning, and 2) reduced catecholamine synthesis in peripheral dopamine β-hydroxylase (DBH)–deficient mice prevented cancer-induced WAT browning and adipose atrophy. Targeting the intraadipose macrophagesympathetic neuron cross-talk represents a promising therapeutic approach to ameliorate cachexia in cancer patients. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
