Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice
Obesity results from a chronic energy imbalance due to energy intake exceeding energy expenditure. Activation of brown fat thermogenesis has been shown to combat obesity. Epigenetic regulation, including DNA methylation, has emerged as a key regulator of brown fat thermogenic function. Here we aimed...
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MDPI AG
2021-11-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/11/12/1325 |
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| author | Fenfen Li Xin Cui Jia Jing Shirong Wang Huidong Shi Bingzhong Xue Hang Shi |
| author_facet | Fenfen Li Xin Cui Jia Jing Shirong Wang Huidong Shi Bingzhong Xue Hang Shi |
| author_sort | Fenfen Li |
| collection | DOAJ |
| description | Obesity results from a chronic energy imbalance due to energy intake exceeding energy expenditure. Activation of brown fat thermogenesis has been shown to combat obesity. Epigenetic regulation, including DNA methylation, has emerged as a key regulator of brown fat thermogenic function. Here we aimed to study the role of Dnmt3b, a DNA methyltransferase involved in de novo DNA methylation, in the regulation of brown fat thermogenesis and obesity. We found that the specific deletion of Dnmt3b in brown fat promotes the thermogenic and mitochondrial program in brown fat, enhances energy expenditure, and decreases adiposity in female mice fed a regular chow diet. With a lean phenotype, the female knockout mice also exhibit increased insulin sensitivity. In addition, Dnmt3b deficiency in brown fat also prevents diet-induced obesity and insulin resistance in female mice. Interestingly, our RNA-seq analysis revealed an upregulation of the PI3K-Akt pathway in the brown fat of female Dnmt3b knockout mice. However, male Dnmt3b knockout mice have no change in their body weight, suggesting the existence of sexual dimorphism in the brown fat Dnmt3b knockout model. Our data demonstrate that Dnmt3b plays an important role in the regulation of brown fat function, energy metabolism and obesity in female mice. |
| first_indexed | 2024-03-10T03:43:04Z |
| format | Article |
| id | doaj.art-7e2308d9659848c2a96e0fe1887e6f88 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T03:43:04Z |
| publishDate | 2021-11-01 |
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| record_format | Article |
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| spelling | doaj.art-7e2308d9659848c2a96e0fe1887e6f882023-11-23T09:13:51ZengMDPI AGLife2075-17292021-11-011112132510.3390/life11121325Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female MiceFenfen Li0Xin Cui1Jia Jing2Shirong Wang3Huidong Shi4Bingzhong Xue5Hang Shi6Department of Biology, Georgia State University, Atlanta, GA 30303, USADepartment of Biology, Georgia State University, Atlanta, GA 30303, USADepartment of Biology, Georgia State University, Atlanta, GA 30303, USADepartment of Biology, Georgia State University, Atlanta, GA 30303, USAGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USADepartment of Biology, Georgia State University, Atlanta, GA 30303, USADepartment of Biology, Georgia State University, Atlanta, GA 30303, USAObesity results from a chronic energy imbalance due to energy intake exceeding energy expenditure. Activation of brown fat thermogenesis has been shown to combat obesity. Epigenetic regulation, including DNA methylation, has emerged as a key regulator of brown fat thermogenic function. Here we aimed to study the role of Dnmt3b, a DNA methyltransferase involved in de novo DNA methylation, in the regulation of brown fat thermogenesis and obesity. We found that the specific deletion of Dnmt3b in brown fat promotes the thermogenic and mitochondrial program in brown fat, enhances energy expenditure, and decreases adiposity in female mice fed a regular chow diet. With a lean phenotype, the female knockout mice also exhibit increased insulin sensitivity. In addition, Dnmt3b deficiency in brown fat also prevents diet-induced obesity and insulin resistance in female mice. Interestingly, our RNA-seq analysis revealed an upregulation of the PI3K-Akt pathway in the brown fat of female Dnmt3b knockout mice. However, male Dnmt3b knockout mice have no change in their body weight, suggesting the existence of sexual dimorphism in the brown fat Dnmt3b knockout model. Our data demonstrate that Dnmt3b plays an important role in the regulation of brown fat function, energy metabolism and obesity in female mice.https://www.mdpi.com/2075-1729/11/12/1325Dnmt3bbrown adipocytesthermogenesisobesity |
| spellingShingle | Fenfen Li Xin Cui Jia Jing Shirong Wang Huidong Shi Bingzhong Xue Hang Shi Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice Life Dnmt3b brown adipocytes thermogenesis obesity |
| title | Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice |
| title_full | Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice |
| title_fullStr | Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice |
| title_full_unstemmed | Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice |
| title_short | Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice |
| title_sort | brown fat dnmt3b deficiency ameliorates obesity in female mice |
| topic | Dnmt3b brown adipocytes thermogenesis obesity |
| url | https://www.mdpi.com/2075-1729/11/12/1325 |
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