Abstract
Growth hormone receptor (GHR) can activate several signaling pathways after binding to growth hormone (GH) to regulate cell growth and development. Sex-linked dwarf (SLD) chickens, normal protein functions are prevented because of exon mutations in the GHR gene, have more severe fat deposition. However, the specific molecular mechanisms responsible for this phenotype remains unclear. We therefore investigated the effect of the GHR gene on adipogenic differentiation of chicken bone marrow mesenchymal stem cells (BMSCs). We found that bone marrow fat deposition was more severe in SLD chickens compared to normal chickens, and the expression of genes related to adipogenic differentiation was enhanced in SLD chicken BMSCs. We also detected enhanced mitochondrial function of BMSCs in SLD chickens. In vitro, overexpression of GHR in chicken BMSCs increased mitochondrial membrane potential but decreased reactive oxygen and ATP contents, oxidative phosphorylation complex enzyme activity, and mitochondrial number. Expression of genes associated with mitochondrial biogenesis and function was repressed during adipogenic differentiation in chicken BMSCs, the adipogenic differentiation capacity of chicken BMSCs was also repressed. With knockdown of GHR, opposite results were observed. We concluded that GHR inhibited adipogenic differentiation of chicken BMSCs by suppressing mitochondrial biogenesis and mitochondrial function.
Highlights
Growth hormone (GH), a peptide hormone regulated by the hypothalamus and secreted by the pituitary gland, binds to cell surface growth hormone receptors to regulate metabolic processes and growth and development (Hu et al, 2021)
Hematoxylin and eosin staining of bone marrow tissues from Sex-linked dwarf (SLD) and normal chickens showed the percentage of fat in bone marrow tissues of SLD chickens was significantly higher than that of normal chickens (Figures 1A–C)
Oil red O staining on bone marrow tissues of SLD and normal chickens showed the percentage of lipid droplets in bone marrow tissues of SLD chickens was higher than that of normal chickens (Figures 1D–F)
Summary
Growth hormone (GH), a peptide hormone regulated by the hypothalamus and secreted by the pituitary gland, binds to cell surface growth hormone receptors to regulate metabolic processes and growth and development (Hu et al, 2021). Growth hormone receptor (GHR), a member of the type I cytokine receptor family, is the key receptor transmembrane protein in the GH–GHR axis. The GHR protein has three primary domains: extracellular, single-pass transmembrane, and cytoplasmic intracellular (Dehkhoda et al, 2018). In sexlinked dwarf (SLD) chickens, normal protein functions are prevented because of exon mutations in the GHR gene, compared with normal chickens (Burnside et al, 1991). Sexlinked dwarf chickens are short, weigh only 60–70% of normal chickens, and have higher feed utilization than normal and more severe fat deposition (Guillaume, 1976). The molecular mechanisms responsible for the SLD phenotype are not clearly understood
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