Patterns of gene expression in muscle and fat in tumor‐bearing rats: Effects of CRF2R agonist on cachexia

Abstract

The hypothesis we tested was that administering corticotropin-releasing factor receptor agonists preserves muscle mass during cancer that is related to changes in tissue gene expression. cDNA microarrays were used to compare mRNAs from muscle and adipose tissues of non-treated and agonist-treated tumor-bearing rats. In muscle of non-tumor-bearing agonist-treated animals we observed decreased expression of genes associated with fatty acid uptake and esterification. In tumor-bearing animals, CRF2R agonist administration produced decreased mRNA content of the atrogene lipin-1. In white adipose tissue, agonist treatment of non-tumor-bearing animals induced genes typically related to muscle structure and function. The fact that this treatment decreased expression of atrogenes could have clinical application. In addition, agonist treatment changed the gene pattern of adipose tissue to render it similar to that of skeletal muscle; thus, treatment with this agonist alters the gene pattern to what could be called "muscularization of white adipose tissue."

Cachexia and sarcopenia: mechanisms and potential targets for intervention

“…Sarcoplasmic reticulum and mitochondria are involved in the process of muscle contraction. Alterations in some of the proteins participating in this synergy -such as mitofusin -have been described in experimental cancer cachexia [21]. Cytokines, TNF-a, in particular, are associated with increased oxidative stress in skeletal muscle during cancer [22].…”

“…Mol Cell Endocrinol 2013, 379: [19][20][21][22][23][24][25][26][27][28][29]. The focus of this review was to discuss promising human physiological systems underpinning the decline of mitochondrial and skeletal muscle health with advancing age while highlighting therapeutic strategies such as aerobic exercise and caloric restriction for combating age-related functional impairments.…”

Treatment with a corticotrophin releasing factor 2 receptor agonist modulates skeletal muscle mass and force production in aged and chronically ill animals

“…This inconsistency can be explained by the known effects of CRF2R activation on another major component of absolute body mass, adipose tissue. Recent reports have shown that the CRF2R has a major role, via both central and peripheral action, in modulating body mass [81-84]. Importantly for this report, it has been observed that peripherally administered CRF2R agonists both increases skeletal muscle mass as well as decreases adipose tissue mass in normal rats [81], most likely by direct activation of CRF2Rs in skeletal muscle and adipose tissue.…”

“…Recent reports have shown that the CRF2R has a major role, via both central and peripheral action, in modulating body mass [81-84]. Importantly for this report, it has been observed that peripherally administered CRF2R agonists both increases skeletal muscle mass as well as decreases adipose tissue mass in normal rats [81], most likely by direct activation of CRF2Rs in skeletal muscle and adipose tissue. Thus, the net effect of CRF2R activation on absolute body mass depends on the relative amounts of skeletal muscle and adipose tissue in an animal.…”

The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms

“…Interestingly, peripheral chronic administration of a CRF 2 agonist in rats reduces white fat mass while inducing expression of typical muscle genes in the WAT. 32 Elsewhere, transgenic expression of the CRF 2 agonist Ucn3 or in vitro stimulation of the CRF 2 pathway with Urocortin 2 activates energy dissipating substrate cycles in the muscle and upregulates UCP2 and UCP3 mRNAs. 9,33 Taking into account that myocytes and brown adipocytes are derived from a common mesenchymal precursor, 28,34 we might speculate for a broader role of the CRF 2 pathway in promoting mitochondrial thermogenesis in peripheral tissues, such as the adipose tissue and skeletal muscle.…”