Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Xie, H; Heier, C; Meng, X; Bakiri, L; Pototschnig, I; Tang, Z; Schauer, S; Baumgartner, VJ; Grabner, GF; Schabbauer, G; Wolinski, H; Robertson, GR; Hoefler, G; Zeng, W; Wagner, EF; Schweiger, M; Zechner, R.
An immune-sympathetic neuron communication axis guides adipose tissue browning in cancer-associated cachexia.
Proc Natl Acad Sci U S A. 2022; 119(9):
Doi: 10.1073/pnas.2112840119
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- Co-authors Med Uni Graz
- Grabner Gernot
- Höfler Gerald
- Schauer Silvia
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- Abstract:
- 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 macrophage-sympathetic neuron cross-talk represents a promising therapeutic approach to ameliorate cachexia in cancer patients.
- Find related publications in this database (using NLM MeSH Indexing)
- Adipose Tissue, Brown - pathology
- Animals - administration & dosage
- Cachexia - etiology, metabolism, pathology
- Cell Communication - administration & dosage
- Gene Expression - administration & dosage
- Heterografts - administration & dosage
- Humans - administration & dosage
- Mice - administration & dosage
- Neoplasms - complications, metabolism
- Neurons - pathology
- Receptors, Adrenergic, beta - metabolism
- Sympathetic Nervous System - pathology
- Thermogenesis - administration & dosage
- Find related publications in this database (Keywords)
- cancer cachexia
- macrophage
- browning
- immunometabolism
- adipose tissue