Abstract
Melatonin (N-acetyl-5-methoxytryptamine) is a derivative of tryptophan which is produced and secreted mainly by the pineal gland and regulates a variety of important central and peripheral actions. To examine the potential effects of melatonin on the proliferation and differentiation of bovine intramuscular preadipocytes (BIPs), BIPs were incubated with different concentrations of melatonin. Melatonin supplementation at 1 mM significantly increased peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein (C/EBP) β, and C/EBPα expression and promoted the differentiation of BIPs into adipocytes with large lipid droplets and high cellular triacylglycerol (TAG) levels. Melatonin also significantly enhanced lipolysis and up-regulated the expression of lipolytic genes and proteins, including hormone sensitive lipase (HSL), adipocyte triglyceride lipase (ATGL), and perilipin 1 (PLIN1). Moreover, melatonin reduced intracellular reactive oxygen species (ROS) levels by increasing the expression levels and activities of superoxide dismutase 1 (SOD1) and glutathione peroxidase 4 (GPX4). Finally, the positive effects of melatonin on adipogenesis, lipolysis, and redox status were reversed by treatment with luzindole, anantagonist of nonspecific melatonin receptors 1 (MT1) and 2 (MT2), and 4-phenyl-2-propionamidotetraline (4P-PDOT), a selective MT2 antagonist. These results reveal that melatonin promotes TAG accumulation via MT2 receptor during differentiation in BIPs.
Highlights
Intramuscular fat (IMF) content, which is termed marbling when visually assessed, plays a critical role in the experience of consuming beef, and a positive relationship between IMF and palatability is well established[1,2]
The results show that the positive effects of 1 mM melatonin on peroxisome proliferator-activated receptor γ (PPARγ), C/EBPβ, and C/EBPα expression are reversed by treatment with 10 μM 4P-PDOT or luzindole (Fig. 7)
We demonstrate for the first time that melatonin promotes the differentiation of bovine intramuscular preadipocytes (BIPs) into adipocytes with large lipid droplets by increasing the expression levels of PPARγ, C/EBPβ, and C/EBPα via a specific melatonin receptor, namely MT2
Summary
Intramuscular fat (IMF) content, which is termed marbling when visually assessed, plays a critical role in the experience of consuming beef, and a positive relationship between IMF and palatability (meat color, flavor, juiciness, and tenderness) is well established[1,2]. Pinealectomized rats exhibit increased accumulation of adipose depots as a result of reduced levels of circulating melatonin[16]. Melatonin stimulates adipocyte differentiation in 3T3-L1 cells and increases intracytoplasmic ATG accumulation in murine fibroblasts by up-regulating PPARγ, C/EBPα, and C/EBPβ21,22. Numerous physiological roles of melatonin are mediated via activation of two high-affinity G protein-coupled receptors, MT1 and MT228,29, which are expressed both singly and together in various tissues with different expression profiles[30,31,32]. Studies related to the melatonin receptor-mediated effects on preadipocyte differentiation in mammals remain elusive
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