Cachexia represents a fatal energy-wasting syndrome in a large number of patients with cancer that mostly results in a pathological loss of skeletal muscle and adipose tissue. Here we show that tumor cell exposure and tumor growth in mice triggered a futile energy-wasting cycle in cultured white adipocytes and white adipose tissue (WAT), respectively. Although uncoupling protein 1 (Ucp1)-dependent thermogenesis was dispensable for tumor-induced body wasting, WAT from cachectic mice and tumor-cell-supernatant-treated adipocytes were consistently characterized by the simultaneous induction of both lipolytic and lipogenic pathways. Paradoxically, this was accompanied by an inactivated AMP-activated protein kinase (Ampk), which is normally activated in peripheral tissues during states of low cellular energy. Ampk inactivation correlated with its degradation and with upregulation of the Ampk-interacting protein Cidea. Therefore, we developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk. Thus, our data establish the Ucp1-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.

• MeSH
• bílá tuková tkáň účinky léků   metabolismus   MeSH
• bílé tukové buňky účinky léků   metabolismus   MeSH
• kachexie etiologie   metabolismus   MeSH
• kultivované buňky MeSH
• lipogeneze účinky léků   MeSH
• lipolýza účinky léků   MeSH
• metabolismus lipidů účinky léků   MeSH
• myši MeSH
• nádory komplikace   metabolismus   MeSH
• peptidové fragmenty farmakologie   MeSH
• proteinkinasy aktivované AMP metabolismus   farmakologie   MeSH
• proteiny regulující apoptózu účinky léků   metabolismus   MeSH
• techniky in vitro MeSH
• termogeneze účinky léků   MeSH
• uncoupling protein 1 účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH