Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1
Summary: Manipulation of energy-dissipating adipocytes has the potential to produce metabolic benefits. To this end, it is valuable to understand the mechanisms controlling the generation and function of thermogenic fat. Here, we identify Letm1 domain containing 1 (Letmd1) as a regulator of brown fa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721015989 |
| _version_ | 1830509065600499712 |
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| author | Kyung-Mi Choi Jung Hak Kim Xiangmudong Kong Meltem Isik Jin Zhang Hee-Woong Lim John C. Yoon |
| author_facet | Kyung-Mi Choi Jung Hak Kim Xiangmudong Kong Meltem Isik Jin Zhang Hee-Woong Lim John C. Yoon |
| author_sort | Kyung-Mi Choi |
| collection | DOAJ |
| description | Summary: Manipulation of energy-dissipating adipocytes has the potential to produce metabolic benefits. To this end, it is valuable to understand the mechanisms controlling the generation and function of thermogenic fat. Here, we identify Letm1 domain containing 1 (Letmd1) as a regulator of brown fat formation and function. The expression of Letmd1 is induced in brown fat by cold exposure and by β-adrenergic activation. Letmd1-deficient mice exhibit severe cold intolerance concomitant with abnormal brown fat morphology, reduced thermogenic gene expression, and low mitochondrial content. The null mice exhibit impaired β3-adrenoreceptor-dependent thermogenesis and are prone to diet-induced obesity and defective glucose disposal. Letmd1 was previously described as a mitochondrial protein, and we find that it also localizes to the nucleus and interacts with the transcriptional coregulator and chromatin remodeler Brg1/Smarca4, thus providing a way to impact thermogenic gene expression. Our study uncovers a role for Letmd1 as a key regulatory component of adaptive thermogenesis. |
| first_indexed | 2024-12-22T01:29:17Z |
| format | Article |
| id | doaj.art-7e2be8fd649b495baef1316673e8cd7e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T01:29:17Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7e2be8fd649b495baef1316673e8cd7e2022-12-21T18:43:32ZengElsevierCell Reports2211-12472021-12-013711110104Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1Kyung-Mi Choi0Jung Hak Kim1Xiangmudong Kong2Meltem Isik3Jin Zhang4Hee-Woong Lim5John C. Yoon6Division of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, CA 95616, USADivision of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, CA 95616, USADepartment of Surgical and Radiological Sciences, University of California Davis School of Veterinary Medicine, Davis, CA 95616, USAVor Biopharma, Cambridge, MA 02140, USADepartment of Surgical and Radiological Sciences, University of California Davis School of Veterinary Medicine, Davis, CA 95616, USADivision of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USADivision of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, CA 95616, USA; Corresponding authorSummary: Manipulation of energy-dissipating adipocytes has the potential to produce metabolic benefits. To this end, it is valuable to understand the mechanisms controlling the generation and function of thermogenic fat. Here, we identify Letm1 domain containing 1 (Letmd1) as a regulator of brown fat formation and function. The expression of Letmd1 is induced in brown fat by cold exposure and by β-adrenergic activation. Letmd1-deficient mice exhibit severe cold intolerance concomitant with abnormal brown fat morphology, reduced thermogenic gene expression, and low mitochondrial content. The null mice exhibit impaired β3-adrenoreceptor-dependent thermogenesis and are prone to diet-induced obesity and defective glucose disposal. Letmd1 was previously described as a mitochondrial protein, and we find that it also localizes to the nucleus and interacts with the transcriptional coregulator and chromatin remodeler Brg1/Smarca4, thus providing a way to impact thermogenic gene expression. Our study uncovers a role for Letmd1 as a key regulatory component of adaptive thermogenesis.http://www.sciencedirect.com/science/article/pii/S2211124721015989Letmd1thermogenesisbrown fat |
| spellingShingle | Kyung-Mi Choi Jung Hak Kim Xiangmudong Kong Meltem Isik Jin Zhang Hee-Woong Lim John C. Yoon Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1 Cell Reports Letmd1 thermogenesis brown fat |
| title | Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1 |
| title_full | Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1 |
| title_fullStr | Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1 |
| title_full_unstemmed | Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1 |
| title_short | Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1 |
| title_sort | defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking letmd1 |
| topic | Letmd1 thermogenesis brown fat |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721015989 |
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