Premium
Biological Sex Mediates Cancer Cachexia Associated Muscle Weakness
Author(s) -
Blackburn George,
Swan Zachary,
Brantley T.J.,
Tichy Louisa,
Parry Traci
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09940
Subject(s) - wasting , cachexia , sarcopenia , grip strength , autophagy , gastrocnemius muscle , medicine , endocrinology , cancer , pathological , skeletal muscle , weakness , inflammation , myostatin , disease , biology , physiology , anatomy , apoptosis , biochemistry
Cancer cachexia is a complex metabolic and wasting disease that results in death in up to one‐third of cancer patients and affects up to 80%. Currently, there are no clear diagnostic criteria, its effects are irreversible, and it cannot be treated. Therefore, a great need exists to better understand this disease. Furthermore, recent evidence states that cancer cachexia presents in a sexually dimorphic manner. Therefore, the purpose of this study was to determine whether cancer cachexia alters skeletal muscle function in a sexually dimorphic manner and to determine underlying mechanisms responsible for muscle wasting. Male and female mice underwent a 3 week period of tumor bearing (1×10 6 LLC cells in flank). Both male and female tumor bearing mice exhibited a loss in grip strength compared to baseline values. Interestingly, males exhibited a significantly greater loss in grip strength compared females (−17% vs −13%, P < 0.05). Male mice also exhibited significantly larger tumors compared to female mice (P < 0.01). Next, possible mechanisms responsible for cancer cachexia‐mediated muscle wasting were investigated. Since protein degratory pathways are known to play an important role in pathological muscle wasting, autophagy was investigated. Interestingly, while both male and female gastrocnemius exhibited an increase in LC3‐II protein levels (increased autophagy) compared to non‐tumor bearing controls, only female gastrocnemius LC3‐II levels were significantly increased (P<0.05). Since inflammation is thought to exacerbate pathological muscle wasting, IL‐1beta was investigated. Both male and female gastrocnemius exhibited increased IL‐1beta compared to non‐tumor bearing controls, though only male gastrocnemius exhibited a significant increase in IL‐1beta protein levels (P < 0.05). These data indicate that cancer cachexia does result in skeletal muscle weakness in a sexually dimprophic manner and that possible underlying mechanisms may differ by biological sex. Such data are critical in elucidating how cancer cachexia variably presents and progresses by biological sex, and in the identification of therapeutic targets aimed at muscle wasting in a sex specific manner.