D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism
The presence of brown adipocytes within white adipose tissue is associated with phenotypes that exhibit improved metabolism and proper body weight maintenance. Therefore, a variety of dietary agents that facilitate the browning of white adipocytes have been investigated. In this study, we screened a...
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MDPI AG
2021-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/4/768 |
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| author | Hui-Jeon Jeon Dong Kyu Choi JaeHeon Choi Seul Lee Heejin Lee Ji Hoon Yu Sang-Hyun Min |
| author_facet | Hui-Jeon Jeon Dong Kyu Choi JaeHeon Choi Seul Lee Heejin Lee Ji Hoon Yu Sang-Hyun Min |
| author_sort | Hui-Jeon Jeon |
| collection | DOAJ |
| description | The presence of brown adipocytes within white adipose tissue is associated with phenotypes that exhibit improved metabolism and proper body weight maintenance. Therefore, a variety of dietary agents that facilitate the browning of white adipocytes have been investigated. In this study, we screened a natural product library comprising 133 compounds with the potential to promote the browning of white adipocytes, and found that D-mannitol induces the browning of 3T3-L1 adipocytes by enhancing the expression of brown fat-specific genes and proteins, and upregulating lipid metabolism markers. D-mannitol also increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase 1 (ACC), suggesting a possible role in lipolysis and fat oxidation. Moreover, an increase in the expression of genes associated with D-mannitol-induced browning was strongly correlated with the activation of the β3-adrenergic receptor as well as AMPK, protein kinase A (PKA), and PPARγ coactivator 1α (PGC1α). D-mannitol effectively reduced the body weight of mice fed a high-fat diet, and increased the expression of β1-oxidation and energy expenditure markers, such as Cidea, carnitine palmityl transferase 1 (CPT1), uncoupling protein 1 (UCP1), PGC1α, and acyl-coenzyme A oxidase (ACOX1) in the inguinal white adipose tissue. Our findings suggest that D-mannitol plays a dual regulatory role by inducing the generation of a brown fat-like phenotype and enhancing lipid metabolism. These results indicate that D-mannitol can function as an anti-obesity supplement. |
| first_indexed | 2024-03-10T12:44:10Z |
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| id | doaj.art-15896f5f3b5f4fcf8e913862749cb291 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:44:10Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-15896f5f3b5f4fcf8e913862749cb2912023-11-21T13:35:32ZengMDPI AGCells2073-44092021-03-0110476810.3390/cells10040768D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent MechanismHui-Jeon Jeon0Dong Kyu Choi1JaeHeon Choi2Seul Lee3Heejin Lee4Ji Hoon Yu5Sang-Hyun Min6New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbok-ro, Dong gu, Daegu 41061, KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbok-ro, Dong gu, Daegu 41061, KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbok-ro, Dong gu, Daegu 41061, KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbok-ro, Dong gu, Daegu 41061, KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbok-ro, Dong gu, Daegu 41061, KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbok-ro, Dong gu, Daegu 41061, KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbok-ro, Dong gu, Daegu 41061, KoreaThe presence of brown adipocytes within white adipose tissue is associated with phenotypes that exhibit improved metabolism and proper body weight maintenance. Therefore, a variety of dietary agents that facilitate the browning of white adipocytes have been investigated. In this study, we screened a natural product library comprising 133 compounds with the potential to promote the browning of white adipocytes, and found that D-mannitol induces the browning of 3T3-L1 adipocytes by enhancing the expression of brown fat-specific genes and proteins, and upregulating lipid metabolism markers. D-mannitol also increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase 1 (ACC), suggesting a possible role in lipolysis and fat oxidation. Moreover, an increase in the expression of genes associated with D-mannitol-induced browning was strongly correlated with the activation of the β3-adrenergic receptor as well as AMPK, protein kinase A (PKA), and PPARγ coactivator 1α (PGC1α). D-mannitol effectively reduced the body weight of mice fed a high-fat diet, and increased the expression of β1-oxidation and energy expenditure markers, such as Cidea, carnitine palmityl transferase 1 (CPT1), uncoupling protein 1 (UCP1), PGC1α, and acyl-coenzyme A oxidase (ACOX1) in the inguinal white adipose tissue. Our findings suggest that D-mannitol plays a dual regulatory role by inducing the generation of a brown fat-like phenotype and enhancing lipid metabolism. These results indicate that D-mannitol can function as an anti-obesity supplement.https://www.mdpi.com/2073-4409/10/4/768obesitybrowningD-mannitolbrown adipocyteβ3-adrenergic receptor |
| spellingShingle | Hui-Jeon Jeon Dong Kyu Choi JaeHeon Choi Seul Lee Heejin Lee Ji Hoon Yu Sang-Hyun Min D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism Cells obesity browning D-mannitol brown adipocyte β3-adrenergic receptor |
| title | D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism |
| title_full | D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism |
| title_fullStr | D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism |
| title_full_unstemmed | D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism |
| title_short | D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism |
| title_sort | d mannitol induces a brown fat like phenotype via a β3 adrenergic receptor dependent mechanism |
| topic | obesity browning D-mannitol brown adipocyte β3-adrenergic receptor |
| url | https://www.mdpi.com/2073-4409/10/4/768 |
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