The Marine Factor 3,5-Dihydroxy-4-methoxybenzyl Alcohol Represses Adipogenesis in Mouse 3T3-L1 Adipocytes In Vitro: Regulating Diverse Signaling Pathways

The augmentation of adipocytes in the adipose tissues brings disordered pathophysiological conditions, including type 2 diabetes, hyperlipidemia, hypertension, cardiovascular disease, and cancer. The phenolic antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) prevents oxidative stress as radi...

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Main Authors: Masayoshi Yamaguchi, Kenji Yoshiike, Hideaki Watanabe, Mitsugu Watanabe
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Nutraceuticals
Subjects:
Online Access:https://www.mdpi.com/1661-3821/3/3/28
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author Masayoshi Yamaguchi
Kenji Yoshiike
Hideaki Watanabe
Mitsugu Watanabe
author_facet Masayoshi Yamaguchi
Kenji Yoshiike
Hideaki Watanabe
Mitsugu Watanabe
author_sort Masayoshi Yamaguchi
collection DOAJ
description The augmentation of adipocytes in the adipose tissues brings disordered pathophysiological conditions, including type 2 diabetes, hyperlipidemia, hypertension, cardiovascular disease, and cancer. The phenolic antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) prevents oxidative stress as radical scavenging in cells. However, the role of the disorder as a pharmacologic factor has been poorly understood. This study elucidates the regulatory effects of DHMBA on adipogenesis in mouse 3T3-L1 adipocytes in vitro. The 3T3-L1 preadipocytes were cultured in DMEM containing 10% calf fetal serum in the presence of DHMBA. Culturing with DHMBA repressed the growth of 3T3-L1 preadipocytes cultured in a medium without differentiation factors. Interestingly, when 3T3-L1 preadipocytes were cultured in a medium including differentiation factors containing insulin, DHMBA did not affect the number of cells with the differentiation process of adipogenesis. Culturing with DHMBA (1, 10, or 100 μM) inhibited lipid accumulation in adipocytes and repressed adipogenesis in 3T3-L1 cells. The potent inhibitory effects of DHMBA on adipogenesis were seen at the later stage of culture. Adipogenesis was inhibited by the presence of wortmannin, PD98059, or Bay 11-7082, which are inhibitors of pathways related to insulin signaling pathway. Notably, the suppressive effects of DHMBA on adipogenesis were expressed by the presence of these inhibitors. DHMBA treatment declined the levels of PPARy and C/EBPα related to preadipocyte differentiation and PI3 kinase 100α, Akt, MAPK, phosphor-MAPK, and mTOR implicated in the insulin signaling pathway, leading to adipogenesis promotion. Thus, DHMBA may inhibit adipogenesis via regulating diverse signaling pathways, providing a new strategy for the therapy of obesity.
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spelling doaj.art-67865c4af8eb4aa98b1dafc7487ed47e2023-11-19T12:16:45ZengMDPI AGNutraceuticals1661-38212023-08-013336637910.3390/nutraceuticals3030028The Marine Factor 3,5-Dihydroxy-4-methoxybenzyl Alcohol Represses Adipogenesis in Mouse 3T3-L1 Adipocytes In Vitro: Regulating Diverse Signaling PathwaysMasayoshi Yamaguchi0Kenji Yoshiike1Hideaki Watanabe2Mitsugu Watanabe3Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, 701 Ilalo Street, Hawaii, HI 96813, USAWatanabe Oyster Laboratory Co., Ltd., 490-3 Shimoongata-cho, Hachioji 192-0154, Tokyo, JapanWatanabe Oyster Laboratory Co., Ltd., 490-3 Shimoongata-cho, Hachioji 192-0154, Tokyo, JapanWatanabe Oyster Laboratory Co., Ltd., 490-3 Shimoongata-cho, Hachioji 192-0154, Tokyo, JapanThe augmentation of adipocytes in the adipose tissues brings disordered pathophysiological conditions, including type 2 diabetes, hyperlipidemia, hypertension, cardiovascular disease, and cancer. The phenolic antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) prevents oxidative stress as radical scavenging in cells. However, the role of the disorder as a pharmacologic factor has been poorly understood. This study elucidates the regulatory effects of DHMBA on adipogenesis in mouse 3T3-L1 adipocytes in vitro. The 3T3-L1 preadipocytes were cultured in DMEM containing 10% calf fetal serum in the presence of DHMBA. Culturing with DHMBA repressed the growth of 3T3-L1 preadipocytes cultured in a medium without differentiation factors. Interestingly, when 3T3-L1 preadipocytes were cultured in a medium including differentiation factors containing insulin, DHMBA did not affect the number of cells with the differentiation process of adipogenesis. Culturing with DHMBA (1, 10, or 100 μM) inhibited lipid accumulation in adipocytes and repressed adipogenesis in 3T3-L1 cells. The potent inhibitory effects of DHMBA on adipogenesis were seen at the later stage of culture. Adipogenesis was inhibited by the presence of wortmannin, PD98059, or Bay 11-7082, which are inhibitors of pathways related to insulin signaling pathway. Notably, the suppressive effects of DHMBA on adipogenesis were expressed by the presence of these inhibitors. DHMBA treatment declined the levels of PPARy and C/EBPα related to preadipocyte differentiation and PI3 kinase 100α, Akt, MAPK, phosphor-MAPK, and mTOR implicated in the insulin signaling pathway, leading to adipogenesis promotion. Thus, DHMBA may inhibit adipogenesis via regulating diverse signaling pathways, providing a new strategy for the therapy of obesity.https://www.mdpi.com/1661-3821/3/3/283,5-dihydroxy-4-methoxybenzyl alcoholadipogenesis3T3-L1 preadipocytesinsulin signaling
spellingShingle Masayoshi Yamaguchi
Kenji Yoshiike
Hideaki Watanabe
Mitsugu Watanabe
The Marine Factor 3,5-Dihydroxy-4-methoxybenzyl Alcohol Represses Adipogenesis in Mouse 3T3-L1 Adipocytes In Vitro: Regulating Diverse Signaling Pathways
Nutraceuticals
3,5-dihydroxy-4-methoxybenzyl alcohol
adipogenesis
3T3-L1 preadipocytes
insulin signaling
title The Marine Factor 3,5-Dihydroxy-4-methoxybenzyl Alcohol Represses Adipogenesis in Mouse 3T3-L1 Adipocytes In Vitro: Regulating Diverse Signaling Pathways
title_full The Marine Factor 3,5-Dihydroxy-4-methoxybenzyl Alcohol Represses Adipogenesis in Mouse 3T3-L1 Adipocytes In Vitro: Regulating Diverse Signaling Pathways
title_fullStr The Marine Factor 3,5-Dihydroxy-4-methoxybenzyl Alcohol Represses Adipogenesis in Mouse 3T3-L1 Adipocytes In Vitro: Regulating Diverse Signaling Pathways
title_full_unstemmed The Marine Factor 3,5-Dihydroxy-4-methoxybenzyl Alcohol Represses Adipogenesis in Mouse 3T3-L1 Adipocytes In Vitro: Regulating Diverse Signaling Pathways
title_short The Marine Factor 3,5-Dihydroxy-4-methoxybenzyl Alcohol Represses Adipogenesis in Mouse 3T3-L1 Adipocytes In Vitro: Regulating Diverse Signaling Pathways
title_sort marine factor 3 5 dihydroxy 4 methoxybenzyl alcohol represses adipogenesis in mouse 3t3 l1 adipocytes in vitro regulating diverse signaling pathways
topic 3,5-dihydroxy-4-methoxybenzyl alcohol
adipogenesis
3T3-L1 preadipocytes
insulin signaling
url https://www.mdpi.com/1661-3821/3/3/28
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