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

Kennaway DJ, Varcoe TJ, Voultsios A, Boden MJ - PLoS ONE (2013)

Bottom Line: The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood.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.

View Article: PubMed Central - PubMed

Affiliation: Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia.

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 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 mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 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 mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 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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Related in: MedlinePlus

Plasma metabolites, insulin, and adipokines in 8 week old wild-type and Bmal1  mice.Plasma glucose (a), free fatty acids (b), insulin (c), adiponectin (d) and leptin (e) levels. Data are the mean ± s.e.m. for n = 4 mice of each genotype at each time point, wild-type mice (open circles) and Bmal1  mice (closed circles). The accompanying histograms represent the estimated marginal means ± s.e.m. of the individual gene expression as calculated from the ANOVA. The shaded areas represent the period of darkness. The symbol * indicates that there was a significant difference (P<0.05) between the genotypes.
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pone-0065255-g001: Plasma metabolites, insulin, and adipokines in 8 week old wild-type and Bmal1 mice.Plasma glucose (a), free fatty acids (b), insulin (c), adiponectin (d) and leptin (e) levels. Data are the mean ± s.e.m. for n = 4 mice of each genotype at each time point, wild-type mice (open circles) and Bmal1 mice (closed circles). The accompanying histograms represent the estimated marginal means ± s.e.m. of the individual gene expression as calculated from the ANOVA. The shaded areas represent the period of darkness. The symbol * indicates that there was a significant difference (P<0.05) between the genotypes.

Mentions: Plasma glucose and free fatty acids were not different between wild-type and Bmal1 mice, however, plasma insulin was lower (P<0.02) and adiponectin (P<0.001) and leptin (P<0.001) were higher in Bmal1 compared to wild-type mice (Fig. 1).


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

Kennaway DJ, Varcoe TJ, Voultsios A, Boden MJ - PLoS ONE (2013)

Plasma metabolites, insulin, and adipokines in 8 week old wild-type and Bmal1  mice.Plasma glucose (a), free fatty acids (b), insulin (c), adiponectin (d) and leptin (e) levels. Data are the mean ± s.e.m. for n = 4 mice of each genotype at each time point, wild-type mice (open circles) and Bmal1  mice (closed circles). The accompanying histograms represent the estimated marginal means ± s.e.m. of the individual gene expression as calculated from the ANOVA. The shaded areas represent the period of darkness. The symbol * indicates that there was a significant difference (P<0.05) between the genotypes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672145&req=5

pone-0065255-g001: Plasma metabolites, insulin, and adipokines in 8 week old wild-type and Bmal1 mice.Plasma glucose (a), free fatty acids (b), insulin (c), adiponectin (d) and leptin (e) levels. Data are the mean ± s.e.m. for n = 4 mice of each genotype at each time point, wild-type mice (open circles) and Bmal1 mice (closed circles). The accompanying histograms represent the estimated marginal means ± s.e.m. of the individual gene expression as calculated from the ANOVA. The shaded areas represent the period of darkness. The symbol * indicates that there was a significant difference (P<0.05) between the genotypes.
Mentions: Plasma glucose and free fatty acids were not different between wild-type and Bmal1 mice, however, plasma insulin was lower (P<0.02) and adiponectin (P<0.001) and leptin (P<0.001) were higher in Bmal1 compared to wild-type mice (Fig. 1).

Bottom Line: The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood.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.

View Article: PubMed Central - PubMed

Affiliation: Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia.

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 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 mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 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 mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 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.

Show MeSH
Related in: MedlinePlus