Melatonin promotes triacylglycerol accumulation via MT2 receptor during differentiation in bovine intramuscular preadipocytes

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.

Melatonin suppresses milk fat synthesis by inhibiting the mTOR signaling pathway via the MT1 receptor in bovine mammary epithelial cells

“…Ten mid‐lactating Holstein dairy cows with similar parity, lactating time, milk production, milk fat, and milk protein were randomly divided into a melatonin‐treated group and untreated group, each with 5 cows. Melatonin‐treated cows were given subcutaneous injections of 4.64 mg melatonin (Sigma) for four consecutive days at 8:00 am based on previous study . Five control cows received the vehicle (absolute ethyl alcohol) only.…”

“…However, Auldist et al found that exogenous melatonin decreased milk yield and increased milk fat content in late lactation. Furthermore, recent studies have shown that melatonin plays important roles in regulating adipose differentiation and fat synthesis . Nevertheless, the regulatory role of melatonin in fat synthesis remains unclear.…”

“…Previous research has shown that the physiological function of melatonin depends on dosage and the expression and distribution of its receptors MT1 and MT2 in cells . For instance, melatonin promotes bovine embryo development via the MT1 receptor but increases TAG content in bovine intramuscular preadipocytes by the MT2 receptor . However, there are few studies relevant to the melatonin receptor–mediated effects on milk fat synthesis in bovine mammary epithelial cells (BMECs).…”

“…Furthermore, recent studies have shown that melatonin plays important roles in regulating adipose differentiation and fat synthesis. [11][12][13][14][15] Nevertheless, the regulatory role of melatonin in fat synthesis remains unclear. Some research showed that melatonin inhibits fat synthesis by reducing the mRNA expression level of key genes such as PPARγ, C/ EBPα, and C/EBPβ of fat synthesis in mouse 3T3-L1 preadipocytes.…”

Melatonin in macrophage biology: Current understanding and future perspectives

“…Uptake of triacylglycerol (TAG) and induction of PPAR‐γ are responsible for the switch to mitochondrial respiration and FAO . Melatonin significantly increases PPAR‐γ expression and promotes TAG accumulation via MT 2 receptor (Figure F) . Therefore, melatonin promotes M2 macrophage polarization via affecting α‐KG accumulation, FAO, and OXPHOS (Figure ).…”