Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism

Kennaway, David John; Varcoe, Tamara Jayne; Voultsios, Athena; Boden, Michael James

doi:10.1371/journal.pone.0065255

Cited by 93Circadian rhythm and melatoninAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism

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Kennaway, David John, Varcoe, Tamara Jayne, Voultsios, Athena, Boden, Michael James·2013·PLoS ONE

DOI 10.1371/journal.pone.0065255PMC PMC3672145

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Abstract

The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight). Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively) on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism.

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Whole-body Bmal1 knockout mice show fasting hypoglycemia, reduced plasma insulin levels and increased adiposity.
“whole-body knockout (KO) mice of Bmal1 show fasting hypoglycemia, reduced plasma insulin levels, increased adiposity [16–18].”
From Circadian control of glucose metabolism (2014) · cites this paper as [18]

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Authors: Kennaway, D. J., Varcoe, T. J., Voultsios, A., & Boden, M. J.
Affiliations: The University of Adelaide (AU)
Corresponding author: Kennaway, David John
ORCID: Kennaway, David John
Varcoe, Tamara Jayne
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2013-06-04
Volume: 8
Issue: 6
Pages: e65255
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0065255
PMC: PMC3672145
OpenAlex: W2075783271
Cited by: 93
References: 39
Citations by year: 2026: 5 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 4 · 2017: 11 · 2016: 9 · 2015: 13 · 2014: 9
FWCI: 5.59
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Medical Research Council
National Health and Medical Research Council (399131)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords: Bmal1, circadian clock, adipose tissue, adipokines, adiponectin, leptin, high-fat diet, adiposity, glucose metabolism, gluconeogenesis, pyruvate tolerance, insulin tolerance, clock gene expression, adipose tissue gene expression, hepatic gene expression, PFKFB3, AdipoR1, AdipoR2, visfatin, resistin
MeSH terms: Adipose Tissue, Animals, Body Weight, Fatty Acids, Nonesterified, Female, Gene Expression Regulation, Glucose, Glucose Tolerance Test, Glycolysis, Insulin, Insulin Resistance, Liver, Male, RNA, Messenger, Pyruvic Acid, Mice, Adipokines, ARNTL Transcription Factors, Diet, High-Fat

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Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism

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