Attenuating Effect of Clock Mutation on Triglyceride Contents in the ICR Mouse Liver under a High-Fat Diet
Abstract
Energy homeostasis is subjected to a circadian control that synchronizes energy intake and expenditure. The transcription factor CLOCK, a key component of the molecular circadian clock, controls many kinds of rhythms, such as those for locomotor activity, body temperature, and metabolic functions. The purpose of the present study is to understand the function of the Clock gene during lipid metabolism in the liver using Clock-mutant mice. Clock-mutant mice with an ICR background were fed a high-fat diet for 13 weeks, and liver triglyceride, serum triglyceride, and serum free fatty acid levels were examined. Triglyceride content in the liver was significantly less increased in Clock-mutant mice on a high-fat diet compared to wild-type mice on a high-fat diet. Acsl4 and Fabp1 mRNA levels in the liver showed daily rhythms in wild-type mice. In contrast, Clock -mutant mice had attenuated daily rhythms of Acsl4 and Fabp1 gene expression in the liver under both normal and high-fat diet conditions compared to wild-type mice. In Clock-mutant mice, suppression of Acsl4 and Fabp1 mRNA in the liver under high-fat diet conditions may have attenuated the accumulation of triglycerides in the liver compared to wild-type mice under the same conditions. In conclusion, the authors demonstrate that mice with a Clock mutation showed less triglyceride accumulation in the liver through the suppression of Acsl4 and Fabp1 gene expression when fed a high-fat diet compared to wild-type mice fed the same diet.
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Other Clock mutant mouse models show different metabolic results, including lack of obesity or weight loss despite lipid imbalance, suggesting the importance of genetic background.
“However, different results have been reported in other Clock mutant mouse models as also lack of obesity or even weight loss, despite lipid imbalance, has been reported suggesting the importance of the genetic background when analyzing the metabolic effects of the Clock gene [13–16].”
From Circadian control of glucose metabolism (2014) · cites this paper as [14]
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- Authors
- Kudo, T., Tamagawa, T., Kawashima, M., Mito, N., & Shibata, S.
- Affiliations
- Waseda University (JP)
- National Institute of Health and Nutrition (JP)
- Corresponding author
- Shibata, Shigenobu
- Venue
- Journal of Biological Rhythms
- Publisher
- SAGE Publications
- Published
- 2007-08
- Volume
- 22
- Issue
- 4
- Pages
- 312-323
- ISSN
- 0748-7304 (ISSN-L)
- 1552-4531
- OpenAlex
- W2044300093
- Cited by
- 81
- References
- 23
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 8 · 2014: 8 · 2013: 4 · 2012: 1
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biological Rhythms (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science Society
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- clock genes, circadian clock, triglyceride accumulation, hepatic lipid metabolism, high-fat diet, ACSL4, FABP1, gene expression rhythms, serum triglycerides, serum free fatty acids, ICR mice
- MeSH terms
- Animals, Circadian Rhythm, Dietary Fats, Fats, Fatty Acids, Gene Expression Regulation, Liver, Mice, Inbred ICR, Time Factors, Triglycerides, Trans-Activators, Mice, CLOCK Proteins
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