Background And Objectives: Expansion of white adipose tissue causes systemic inflammation and increased risk of metabolic diseases due to its endocrine function. Resveratrol was suggested to be able to prevent obesity-related disorders by mimicking caloric restriction; however, its structure-activity relationships and molecular targets are still unknown. We aimed to compare the effects of resveratrol and its analogues on adipocyte metabolism and lipid accumulation in vitro.
Methods: Mouse embryonic fibroblasts were differentiated to adipocytes in the absence or presence of resveratrol or its derivatives (oxyresveratrol, monomethylated resveratrol, or trimethylated resveratrol). Intracellular lipid content was assessed by Oil Red O staining. Glucose uptake and its response to insulin were estimated by 2-NBDG, and mitochondrial activity was assayed via resazurin reduction. Involvement of potential molecular pathways was investigated by concurrent treatment with their inhibitors.
Results: Although lipid accumulation was significantly reduced by all analogues without altering protein content, oxyresveratrol was the most potent (IC50 = 4.2 μM), while the lowest potency was observed with trimethylated resveratrol (IC50 = 27.4 μM). Increased insulin-stimulated glucose uptake was restored by each analogue with comparable efficiency. The enhanced mitochondrial activity was normalized by resveratrol and its methylated derivatives, while oxyresveratrol had a minor impact on it. Among the examined pathways, inhibition of SIRT1, PGC-1α, and JNK diminished the lipid-reducing effect of the compounds. Autophagy appeared to play a key role in the effect of all compounds but oxyresveratrol.
Conclusions: Resveratrol and its analogues can mimic caloric restriction with complex mechanisms, including activation of SIRT1, PGC-1α, and JNK, making them possible drug candidates to treat obesity-related diseases.
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http://dx.doi.org/10.3390/nu16223869 | DOI Listing |
Curr Med Chem
January 2025
Transplant Research Center, Clinical Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
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Key Laboratory of Northwest China's Pig Breading and Reproduction, Ministry of Agriculture and Rural Affairs of the People's Republic of China, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
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Department of Immunology and Regenerative Biology, Weizmann Institute of Science, 76100, Rehovot, Israel.
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School of Petrochemical Engineering & Environment, Zhejiang Ocean University, Zhoushan, 316000, China; National & Local Joint Engineering Research Center of Harbor Oil & Gas Storage and Transportation Technology, Zhejiang Key Laboratory of Petrochemical Environmental Pollution Control, Zhoushan, 316000, China. Electronic address:
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SnRK1 (SNF1-related kinase 1), a member of the SNF1 protein kinase superfamily, has been demonstrated to play a role in plant growth and development, as well as in stress responses. In this experiment, the leaf senescence of 'Xintaimici' cucumber was simulated by dark treatment and studied using SnRK1 activator/inhibitor and transient transformation technology. The effects of SnRK1 on cucumber leaf senescence, reactive oxygen species (ROS) metabolism, chloroplast structure, and photosynthetic characteristics were studied.
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