Apr 6, 2020

Breast cancer-associated skeletal muscle mitochondrial dysfunction and lipid accumulation is reversed by PPARG

BioRxiv : the Preprint Server for Biology
H. E. WilsonEmidio E Pistilli

Abstract

The peroxisome-proliferator activated receptors (PPARs) have been previously implicated in the pathophysiology of skeletal muscle dysfunction in women with breast cancer (BC) and in animal models of BC. Here, we sought to describe the metabolic alterations induced in skeletal muscle by BC-derived factors in an in vitro conditioned media (CM) system and hypothesized that BC cells secrete a factor that represses PPAR-gamma (PPARG) expression and its transcriptional activity, leading to downregulation of PPARG target genes involved in mitochondrial function and other metabolic pathways. We found that BC-derived factors repress PPAR-mediated transcriptional activity without altering protein expression of PPARG. Further, we show that BC-derived factors induce significant alterations in skeletal muscle mitochondrial function and lipid metabolism, which are rescued with exogenous expression of PPARG. The PPARG agonist drug rosiglitazone was able to rescue BC-induced lipid accumulation, but did not rescue effects of BC-derived factors on PPAR-mediated transcription or mitochondrial function. These data suggest that BC-derived factors induce deficits in lipid metabolism and mitochondrial function via different mechanisms that are both r...Continue Reading

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Mentioned in this Paper

Muscle Rigidity
Biochemical Pathway
Size
Body Fluid Compartments
Reconstructive Surgical Procedures
Neurons
Neuroanatomy
Drosophila
Locomotion
Larva

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