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Open AccessArticle

Phlorotannins from Ecklonia cava Attenuates Palmitate-Induced Endoplasmic Reticulum Stress and Leptin Resistance in Hypothalamic Neurons

1
Functional Cellular Networks Laboratory, College of Medicine, Department of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea
2
Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea
3
Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Mar. Drugs 2019, 17(10), 570; https://doi.org/10.3390/md17100570
Received: 2 September 2019 / Revised: 30 September 2019 / Accepted: 8 October 2019 / Published: 9 October 2019
(This article belongs to the Collection Marine Drugs in the Management of Metabolic Diseases)
Leptin resistance in the hypothalamus has an essential role in obesity. Saturated fatty acids such as palmitate bind to Toll-like receptor 4 (TLR4) and lead to endoplasmic reticulum (ER) stress and leptin resistance. In this study, we evaluated whether extracts of Ecklonia cava would attenuate the ER stress induced by palmitate and reduce leptin resistance in hypothalamic neurons and microglia. We added palmitate to these cells to mimic the environment induced by high-fat diet in the hypothalamus and evaluated which of the E. cava phlorotannins—dieckol (DK), 2,7-phloroglucinol-6,6-bieckol (PHB), pyrogallol-phloroglucinol-6,6-bieckol (PPB), or phlorofucofuroeckol-A (PFFA)—had the most potent effect on attenuating leptin resistance. TLR4 and NF-κB expression induced by palmitate was attenuated most effectively by PPB in both hypothalamic neurons and microglia. ER stress markers were increased by palmitate and were attenuated by PPB in both hypothalamic neurons and microglia. Leptin resistance, which was evaluated as an increase in SOCS3 and a decrease in STAT3 with leptin receptor expression, was increased by palmitate and was decreased by PPB in hypothalamic neurons. The culture medium from palmitate-treated microglia increased leptin resistance in hypothalamic neurons and this resistance was attenuated by PPB. In conclusion, PPB attenuated leptin resistance by decreasing ER stress in both hypothalamic neurons and microglia. View Full-Text
Keywords: obesity; Ecklonia cava; phlorotannins; hypothalamic neurons; microglia; toll-like receptor 4; endoplasmic reticulum stress; leptin resistance obesity; Ecklonia cava; phlorotannins; hypothalamic neurons; microglia; toll-like receptor 4; endoplasmic reticulum stress; leptin resistance
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Oh, S.; Son, M.; Choi, J.; Choi, C.H.; Park, K.Y.; Son, K.H.; Byun, K. Phlorotannins from Ecklonia cava Attenuates Palmitate-Induced Endoplasmic Reticulum Stress and Leptin Resistance in Hypothalamic Neurons. Mar. Drugs 2019, 17, 570.

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