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Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis
Open accessAbstract
Brain and muscle Arnt-like protein-1 (BMAL1; also known as MOP3 or Arnt3) is a transcription factor known to regulate circadian rhythm. Here, we established its involvement in the control of adipogenesis and lipid metabolism activity in mature adipocytes. During adipose differentiation in 3T3-L1 cells, the level of BMAL1 mRNA began to increase 4 days after induction and was highly expressed in differentiated cells. In white adipose tissues isolated from C57BL/6J mice, BMAL1 was predominantly expressed in a fraction containing adipocytes, as compared with the stromal-vascular fraction. BMAL1 knockout mice embryonic fibroblast cells failed to be differentiated into adipocytes. Importantly, adding BMAL1 back by adenovirus gene transfer restored the ability of BMAL1 knockout mice embryonic fibroblast cells to differentiate. Knock-down of BMAL1 expression in 3T3-L1 cells by an RNA interference technique allowed the cells to accumulate only minimum amounts of lipid droplets in the cells. Adenovirus-mediated expression of BMAL1 in 3T3-L1 adipocytes resulted in induction of several factors involved in lipogenesis. The promoter activity of these genes was stimulated in a BMAL1-dependent manner. Interestingly, expression of these factors showed clear circadian rhythm in mice adipose tissue. Furthermore, overexpression of BMAL1 in adipocytes increased lipid synthesis activity. These results indicate that BMAL1, a master regulator of circadian rhythm, also plays important roles in the regulation of adipose differentiation and lipogenesis in mature adipocytes.
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“Knockout of Bmal1 alone in C57BL/6J mice showed that isolated mouse embryonic fibroblast (MEF) cells could not successfully differentiate into adipocytes (Shimba et al., 2005).”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Shimba et al., 2005
In the citing paper
“The presence of high Bmal1 mRNA levels in adipocytes increased lipogenesis activity, further suggesting that Bmal1 is involved in regulating lipid metabolism.”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Shimba et al., 2005
In the citing paper
“Further, restoration of Bmal1 function by adenovirus gene transfer into the initial Bmal1-deficient mice restored adipocyte differentiation and lipid accumulation in the MEF cells.”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Shimba et al., 2005
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Metadata
- Authors
- Shimba, S., Ishii, N., Ohta, Y., Ohno, T., Watabe, Y., Hayashi, M., Wada, T., Aoyagi, T., & Tezuka, M.
- Affiliations
- Nihon University (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-08-10
- Volume
- 102
- Issue
- 34
- Pages
- 12071-12076
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1189312
- OpenAlex
- W2047902467
- Cited by
- 536
- References
- 39
- Citations by year
- 2026: 15 · 2025: 11 · 2024: 21 · 2023: 21 · 2022: 22 · 2021: 28 · 2020: 19 · 2019: 16 · 2018: 22 · 2017: 24 · 2016: 19 · 2015: 24 · 2014: 33 · 2013: 40 · 2012: 32
- FWCI
- 9.44
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Nihon University
- Ono Medical Research Foundation
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- Bmal1, circadian clock, adipogenesis, lipogenesis, lipid metabolism, 3T3-L1 cells, adipose tissue, circadian rhythm, transcription factors, adipocytes, lipid droplets, gene knockdown, adenoviral gene transfer
- MeSH terms
- Adenoviridae, Adipose Tissue, Animals, Brain, Circadian Rhythm, Gene Expression Regulation, Genetic Vectors, Male, Mice, Inbred C57BL, Immunoblotting, 3T3 Cells, DNA Primers, Gene Transfer Techniques, Muscle, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Chromatin Immunoprecipitation, Adipogenesis, Lipid Metabolism, Mice, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, ARNTL Transcription Factors
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