esculetin and Obesity

Observational human data and several lines of animal experimental data indicate that maternal obesity impairs offspring health. Here, we comprehensively tested the model that maternal obesity causes defects in the next three generations of oocytes and embryos. We exposed female F0 mice to a high-fat/high-sugar (HF/HS) diet for 6 weeks before conception until weaning. Sires, F1 offspring and all subsequent generations were fed control chow diet. Oocytes from F1, F2 and F3 offspring of obese mothers had lower mitochondrial mass and less ATP and citrate than oocytes from offspring of control mothers. F0 blastocysts from HF/HS-exposed mice, but not F1 and F2 blastocysts, had lower mitochondrial mass and membrane potential, less citrate and ATP and smaller total cell number than F0 blastocysts from control mothers. Finally, supplementation of IVF media with the anti-oxidant mito-esculetin partially prevented the oocyte mitochondrial effects caused by maternal HF/HS diet. Our results support the idea that maternal obesity impairs offspring oocyte quality and suggest that antioxidant supplementation should be tested as a means to improve IVF outcomes for obese women.

Topics: Animals; Antioxidants; Apoptosis; Cell Line; Diet, High-Fat; Embryonic Development; Female; Fertilization in Vitro; HEK293 Cells; Humans; Maternal Exposure; Maternal Nutritional Physiological Phenomena; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; Mitochondria; Obesity; Oocytes; Pregnancy; Prenatal Exposure Delayed Effects; Sugars; Umbelliferones

In continuation of evaluating the anti-obesity effect of Aegle marmelos, we have screened the n-hexane, dichloro methane (DCM), ethyl acetate (EtOAc) and methanol (MeOH) extracts of the leaves at the concentration of 25, 50, 75 and 100 μg/ml for adipogenesis inhibition in the adipocytes. Nile red staining with the help of fluorometry was used as indicator of the antiobesity activity. The most active DCM extract showed the 33.98±3.55% lipid content at 100μg/ml and was selected for the further isolation. 14 compounds were isolated from DCM extract of A. marmelos leaves. The compounds were screened for the adipogenesis inhibition at 50 and 100 μM concentrations. Out of the 14 compounds, halfordinol, ethyl ether aegeline and esculetin were showing 10.04±0.52, 16.29±0.85 and 25.09±1.31% lipid content respectively at 100 μM. We hereby report the adipogenesis inhibition by A. marmelos as one of the pathway for its antiobesity effect.

Topics: 3T3-L1 Cells; Adipogenesis; Adipose Tissue; Aegle; Amides; Animals; Anti-Obesity Agents; Lipid Metabolism; Mice; Obesity; Plant Extracts; Umbelliferones