Ganglioside GM3 prevents high fat diet-induced hepatosteatosis via attenuated insulin signaling pathway

被引:3
作者
Tajima, Orie [1 ]
Fujita, Yuki [1 ,2 ]
Ohmi, Yuhsuke [3 ]
Furukawa, Koichi [1 ]
Furukawa, Keiko [1 ]
机构
[1] Chubu Univ, Coll Life & Hlth Sci, Dept Biomed Sci, Kasugai, Japan
[2] Aichi Med Univ Hosp, Dept Clin Lab, Nagakute, Japan
[3] Chubu Univ, Coll Life & Hlth Sci, Dept Clin Engn, Kasugai, Japan
基金
日本科学技术振兴机构;
关键词
MALIGNANT PROPERTIES; HEPATIC STEATOSIS; MELANOMA-CELLS; LIPID RAFTS; SENSITIVITY; MICE; EXPRESSION; MAINTENANCE; INHIBITION; METABOLISM;
D O I
10.1371/journal.pone.0281414
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Gangliosides, sialic acid-containing glycosphingolipids, are widely involved in regulations of signal transductions to control cellular functions. It has been suggested that GM3, the simplest structure among gangliosides, is involved in insulin resistance, whereas it remains unclear whether insulin signaling diminished by GM3 actually aggravates the pathological conditions in metabolic disorders. Moreover, the functional roles of gangliosides in the regulation of insulin signaling have not yet been fully elucidated in liver or hepatocytes despite that it is one of the major insulin-sensitive organs. To understand physiological roles of GM3 in metabolic homeostasis in liver, we conducted a high fat diet (HFD) loading experiment using double knockout (DKO) mice of GM2/GD2 synthase and GD3 synthase, which lack all gangliosides except GM3, as well as wild-type (WT) mice. DKO mice were strikingly resistant to HFD-induced hepatosteatosis, and hepatic lipogenesis-related molecules including insulin signaling components were down-regulated in HFD-fed DKO. Furthermore, we established primary hepatocyte cultures from DKO and WT mice, and examined their responses to insulin in vitro. Following insulin stimulation, DKO hepatocytes expressing GM3 showed attenuated expression and/or activations in the downstream components compared with WT hepatocytes expressing GM2. While insulin stimulation induced lipogenic proteins in hepatocytes from both genotypes, their expression levels were lower in DKO than in WT hepatocytes after insulin treatment. All our findings suggest that the modified gangliosides, i.e., a shift to GM3 from GM2, might exert a suppressive effect on lipogenesis by attenuating insulin signaling at least in mouse hepatocytes, which might result in protection of HFD-induced hepatosteatosis.
引用
收藏
页数:20
相关论文
共 50 条
[21]   Curcumin Prevents High Fat Diet Induced Insulin Resistance and Obesity via Attenuating Lipogenesis in Liver and Inflammatory Pathway in Adipocytes [J].
Shao, Weijuan ;
Yu, Zhiwen ;
Chiang, Yuting ;
Yang, Yi ;
Chai, Tuanyao ;
Foltz, Warren ;
Lu, Huogen ;
Fantus, I. George ;
Jin, Tianru .
PLOS ONE, 2012, 7 (01)
[22]   D-chiro-Inositol Ameliorates High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance via PKCε-PI3K/AKT Pathway [J].
Cheng, Feier ;
Han, Lin ;
Xiao, Yao ;
Pan, Chuanying ;
Li, Yunlong ;
Ge, Xinhui ;
Zhang, Yao ;
Yan, Shaoqing ;
Wang, Min .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2019, 67 (21) :5957-5967
[23]   Lactobacillus plantarum ZJUFB2 Prevents High Fat Diet-Induced Insulin Resistance in Association With Modulation of the Gut Microbiota [J].
Zhong, Hao ;
Wang, Jian ;
Abdullah ;
Hafeez, Muhammad Adnan ;
Guan, Rongfa ;
Feng, Fengqin .
FRONTIERS IN NUTRITION, 2021, 8
[24]   Probiotic Yogurt Alleviates High-Fat Diet-Induced Lipid Accumulation and Insulin Resistance in Mice via the Adiponectin Pathway [J].
Tang, Chao ;
Zhao, Hongyuan ;
Kong, Liangyu ;
Meng, Fanqiang ;
Zhou, Libang ;
Lu, Zhaoxin ;
Lu, Yingjian .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2023, 71 (03) :1464-1476
[25]   Analysis of the liver lipidome reveals insights into the protective effect of exercise on high-fat diet-induced hepatosteatosis in mice [J].
Jordy, Andreas B. ;
Kraakman, Michael J. ;
Gardner, Tim ;
Estevez, Emma ;
Kammoun, Helene L. ;
Weir, Jacqui M. ;
Kiens, Bente ;
Meikle, Peter J. ;
Febbraio, Mark A. ;
Henstridge, Darren C. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2015, 308 (09) :E778-E791
[26]   Diosgenin prevents high-fat diet-induced rat non-alcoholic fatty liver disease through the AMPK and LXR signaling pathways [J].
Cheng, Silu ;
Liang, Shufang ;
Liu, Qun ;
Deng, Zhengting ;
Zhang, Yuanhui ;
Du, Juan ;
Zhang, Ya'ni ;
Li, Shu ;
Cheng, Binbin ;
Ling, Changquan .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2018, 41 (02) :1089-1095
[27]   Oleacein Prevents High Fat Diet-Induced Adiposity and Ameliorates Some Biochemical Parameters of Insulin Sensitivity in Mice [J].
Lepore, Saverio Massimo ;
Maggisano, Valentina ;
Bulotta, Stefania ;
Mignogna, Chiara ;
Arcidiacono, Biagio ;
Procopio, Antonio ;
Brunetti, Antonio ;
Russo, Diego ;
Celano, Marilena .
NUTRIENTS, 2019, 11 (08)
[28]   DBZ is a putative PPARγ agonist that prevents high fat diet-induced obesity, insulin resistance and gut dysbiosis [J].
Xu, Pengfei ;
Hong, Fan ;
Wang, Jialin ;
Wang, Jing ;
Zhao, Xia ;
Wang, Sheng ;
Xue, Tingting ;
Xu, Jingwei ;
Zheng, Xiaohui ;
Zhai, Yonggong .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2017, 1861 (11) :2690-2701
[29]   Inhibiting myeloperoxidase prevents onset and reverses established high-fat diet-induced microvascular insulin resistance [J].
Chai, Weidong ;
Aylor, Kevin ;
Liu, Zhenqi ;
Gan, Li-Ming ;
Michaelsson, Erik ;
Barrett, Eugene .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2019, 317 (06) :E1063-E1069
[30]   Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance [J].
Kraakman, Michael J. ;
Kammoun, Helene L. ;
Allen, Tamara L. ;
Deswaerte, Virginie ;
Henstridge, Darren C. ;
Estevez, Emma ;
Matthews, Vance B. ;
Neill, Bronwyn ;
White, David A. ;
Murphy, Andrew J. ;
Peijs, Lone ;
Yang, Christine ;
Risis, Steve ;
Bruce, Clinton R. ;
Du, Xiao-Jun ;
Bobik, Alex ;
Lee-Young, Robert S. ;
Kingwell, Bronwyn A. ;
Vasanthakumar, Ajithkumar ;
Shi, Wei ;
Kallies, Axel ;
Lancaster, Graeme I. ;
Rose-John, Stefan ;
Febbraio, Mark A. .
CELL METABOLISM, 2015, 21 (03) :403-416