umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
β3-adrenergic antagonism alleviates weight loss associated with cancer cachexia
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
2017 (English)Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Cancer induced cachexia (CIC) is a devastating wasting disorder affecting people with tumor diseases and is deemed responsible for approximately 20% of all cancer-related deaths. This syndrome is associated with atrophy of adipose tissue and skeletal muscle. No established treatment is available for CIC and the underlying mechanisms are unveiled. However, one proposed culprit is brown adipose tissue (BAT) and browning of white adipose tissue (WAT), which produces heat via activation uncoupling protein 1 (UCP1). The result is increased energy wasting. Β3-adrenergic receptor (ADRB3) signaling activates BAT and we hypothesized that treatment with a specific ADRB3 antagonist would mitigate energy wasting in CIC. Balb/ca nude mice implanted with the LuCAP32 human xenograft tumor was used as a model system for CIC. The mice were treated with the selective ADRB3-blocker SR59230A and the unselective ADRB1 and 2-blocker propranolol for 4 weeks. A vehicle (VEH) and non-tumor bearing (NTB) group was also used. Significant effects were seen on total body weight loss with SR-treatment compared to VEH. Similar effects were seen on the wasting of local WAT depots. When measuring body composition, we found moderate evidence that SR spares the wasting of lean mass. We were also able to show decreased gene expression of BAT-markers, as well as markers for lipolysis, in the subcutaneous WAT. This supports our main hypothesis. In conclusion, we can show that treatment with a selective ADRB3 antagonist alleviates the symptoms of CIC through decreased lipolysis and decreased browning of WAT. These findings add to the mechanistic understanding of the pathophysiology of CIC and could be a potential treatment strategy for this syndrome.

Place, publisher, year, edition, pages
2017. , p. 13
National Category
Other Medical Biotechnology
Identifiers
URN: urn:nbn:se:umu:diva-143518OAI: oai:DiVA.org:umu-143518DiVA, id: diva2:1170427
Educational program
Medical Programme
Supervisors
Examiners
Available from: 2018-06-25 Created: 2018-01-03 Last updated: 2018-06-25Bibliographically approved

Open Access in DiVA

No full text in DiVA

By organisation
Physiological chemistry
Other Medical Biotechnology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 339 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf