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Tissue-specific dysregulation of mitochondrial respiratory capacity and coupling control in colon-26 tumor-induced cachexia.
Halle, Jessica L; Pena, Gabriel S; Paez, Hector G; Castro, Adrianna J; Rossiter, Harry B; Visavadiya, Nishant P; Whitehurst, Michael A; Khamoui, Andy V.
Afiliación
  • Halle JL; Department of Exercise Science and Health Promotion, Florida Atlantic University , Boca Raton, Florida.
  • Pena GS; Department of Exercise Science and Health Promotion, Florida Atlantic University , Boca Raton, Florida.
  • Paez HG; Department of Exercise Science and Health Promotion, Florida Atlantic University , Boca Raton, Florida.
  • Castro AJ; Department of Exercise Science and Health Promotion, Florida Atlantic University , Boca Raton, Florida.
  • Rossiter HB; Division of Respiratory and Critical Care Physiology and Medicine, Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center , Torrance, California.
  • Visavadiya NP; Faculty of Biological Sciences, University of Leeds , Leeds , United Kingdom.
  • Whitehurst MA; Department of Exercise Science and Health Promotion, Florida Atlantic University , Boca Raton, Florida.
  • Khamoui AV; Department of Exercise Science and Health Promotion, Florida Atlantic University , Boca Raton, Florida.
Am J Physiol Regul Integr Comp Physiol ; 317(1): R68-R82, 2019 07 01.
Article en En | MEDLINE | ID: mdl-31017805
In addition to skeletal muscle dysfunction, cancer cachexia is a systemic disease involving remodeling of nonmuscle organs such as adipose and liver. Impairment of mitochondrial function is associated with multiple chronic diseases. The tissue-specific control of mitochondrial function in cancer cachexia is not well defined. This study determined mitochondrial respiratory capacity and coupling control of skeletal muscle, white adipose tissue (WAT), and liver in colon-26 (C26) tumor-induced cachexia. Tissues were collected from PBS-injected weight-stable mice, C26 weight-stable mice and C26 mice with moderate (10% weight loss) and severe cachexia (20% weight loss). The respiratory control ratio [(RCR) an index of oxidative phosphorylation (OXPHOS) coupling efficiency] was low in WAT during the induction of cachexia because of high nonphosphorylating LEAK respiration. Liver RCR was low in C26 weight-stable and moderately cachexic mice because of reduced OXPHOS. Liver RCR was further reduced with severe cachexia, where Ant2 but not Ucp2 expression was increased. Ant2 was inversely correlated with RCR in the liver (r = -0.547, P < 0.01). Liver cardiolipin increased in moderate and severe cachexia, suggesting this early event may also contribute to mitochondrial uncoupling. Impaired skeletal muscle mitochondrial respiration occurred predominantly in severe cachexia, at complex I. These findings suggest that mitochondrial function is subject to tissue-specific control during cancer cachexia, whereby remodeling in WAT and liver arise early and may contribute to altered energy balance, followed by impaired skeletal muscle respiration. We highlight an under-recognized role of liver and WAT mitochondrial function in cancer cachexia and suggest mitochondrial function of multiple tissues to be therapeutic targets.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Consumo de Oxígeno / Caquexia / Mitocondrias Musculares / Neoplasias Experimentales Límite: Animals Idioma: En Revista: Am J Physiol Regul Integr Comp Physiol Asunto de la revista: FISIOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Consumo de Oxígeno / Caquexia / Mitocondrias Musculares / Neoplasias Experimentales Límite: Animals Idioma: En Revista: Am J Physiol Regul Integr Comp Physiol Asunto de la revista: FISIOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos