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Trigonelline induces browning in 3T3-L1 white adipocytes
Minji Choi1, Sulagna Mukherjee1, Jong Won Yun1
1Department of Biotechnology, Daegu University, Gyeongsan, South Korea.
Abstract:
Trigonelline, a major alkaloid component of fenugreek, has been demonstrated to have several biological activities, including antidiabetic and anticancer effects. This study aimed to examine the possible application of trigonelline as an anti-obesity compound based on an investigation of its enhancement of lipid catabolism and induction of browning in white adipocytes. Trigonelline induces browning of 3T3-L1 white adipocytes by enhancing the expressions of brown-fat signature proteins and genes as well as beige-specific genes, including Cd137, Cited1, Tbx1, and Tmem26. Trigonelline also improves lipid metabolism in white adipocytes by decreasing adipogenesis and lipogenesis as well as promotes lipolysis and fatty acid oxidation. Moreover, trigonelline increases the expression of Cox4, Nrf1, and Tfam genes that are responsible for mitochondrial biogenesis. Mechanistic studies revealed that the browning effect of trigonelline in 3T3-L1 white adipocytes is mediated by activating β3-AR and inhibiting PDE4, thereby stimulating the p38 MAPK/ATF-2 signaling pathway. Considering its high bioavailability in humans and the results of this study, trigonelline may have potential as an anti-obesity compound.
Insights
Trigonelline, found in fenugreek, may combat obesity by promoting "browning" in fat cells and enhancing fat breakdown. This natural compound shows promise for weight management due to its effects on lipid metabolism.
Area of Science:
- Metabolic research
- Cell biology
- Pharmacology
Background:
- Fenugreek alkaloid trigonelline exhibits antidiabetic and anticancer properties.
- Obesity is a growing health concern requiring novel therapeutic strategies.
- Understanding mechanisms of fat metabolism is crucial for developing anti-obesity treatments.
Purpose of the Study:
- To investigate trigonelline's potential as an anti-obesity agent.
- To examine trigonelline's effects on lipid catabolism and adipocyte browning.
- To elucidate the molecular pathways involved in trigonelline's action.
Main Methods:
- Utilized 3T3-L1 white adipocytes to study trigonelline's effects.
- Assessed gene and protein expression related to brown fat and lipid metabolism.
- Investigated signaling pathways including β3-AR, PDE4, and MAPK/ATF-2.
Main Results:
- Trigonelline induced browning in white adipocytes by upregulating key brown-fat signature genes.
- Trigonelline improved lipid metabolism by reducing adipogenesis and lipogenesis, and increasing lipolysis and fatty acid oxidation.
- Trigonelline enhanced mitochondrial biogenesis through increased expression of related genes.
- Mechanistically, trigonelline's browning effect was mediated by β3-AR activation and PDE4 inhibition, activating the p38 MAPK/ATF-2 pathway.
Conclusions:
- Trigonelline demonstrates significant potential as an anti-obesity compound.
- Its ability to induce browning and enhance lipid catabolism in adipocytes supports its therapeutic application.
- High bioavailability in humans further supports its consideration for anti-obesity strategies.
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