Ellagic Acid Alleviates Abnormal Fat Reduction by Activating the RXRβ-PPARγ Pathways in a CT26 Tumour-Induced Cachexia Mouse Model

Authors
Woo Yong Park, Beomsu Kim, Gahee Song, Sang Hee Kim, Jin-Hyung Kim, Ja Yeon Park, Se Jin Jung, Wenjun Jiao, Jisoo Han, Taekyoung Kong, Kwang Seok Ahn, Hyun Jeong Kwak, Jae-Young Um


Lab

Journal
Journal of Cachexia, Sarcopenia and Muscle

Abstract
To establish an in vitro model mimicking fat loss induced by cancer cachexia, we used CT26 mouse colon cancer cells. CM was collected from CT26 cells cultured under nutrient-restricted conditions (1% FBS), and the pro-inflammatory cytokines IL-6 and TNF-α were quantified (Figure1A). CT26 cells cultured with 1% FBS for 2 days secreted IL-6, but not TNF-α (Figures1BandS1A). Based on the results, we chose Day 2 (2nd CM) as the optimal time for collecting the CM. To determine the optimal CM concentration, Oil Red O staining was performed on white adipocytes treated with 25%, 50% or 75% CM. Lipid accumulation in white adipocytes was reduced at all CM concentrations, with the optimal condition achieved using a 1:1 mixture of CM and plain DMEM (CM 50%) (FigureS1B). To investigate whether EA protects against CM-induced reduction in lipid accumulation, Oil Red O staining was performed and quantified in CM-stimulated white adipocytes treated with EA (3.1, 6.3 and 12.5 μM). EA treatment significantly increased the lipid accumulation in CM-stimulated white adipocytes (Figure1C,D). To verify the restoration of the altered lipid metabolism in CM-stimulated white adipocytes treated with EA, we extracted the crude lipid fraction from the cells, collected the supernatants and evaluated the amount of FA. The CM treatment in white adipocytes resulted in an increased intracellular FA, whereas the EA treatment restored the levels of FA to those of the white adipocytes. The extracellular levels of free FAs were not altered (Figure1E). Given that adipokines regulate adipogenesis, adipocyte metabolism and function [S6], we performed adipoikine proteomic profiling using the Proteome Profiler Mouse Adipokine Array Kit to identify the alterations in adipokine production following CM treatment. The supernatant from CM–treated white adipocytes contained 13 different adipokines (Figure1F,Gand TableS1). Among these, three adipokines (endocan, RANTES and serpin E1) were increased, and two (IGFBP-3 and lipocalin-2) were decreased. We further investigated whether EA treatment can reverse these changes. EA restored the levels of IGFBP-3 and lipocalin-2, which were similar to those observed in white adipocytes (Figure1H).

Keywords/Topics
abnormal fat reduction; cancer cachexia; ellagic acid; PPARγ; RXRβ

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcsm.70176

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