Limits...
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.

Show MeSH

Related in: MedlinePlus

The relative gene expression across 24 h of clock and other genes in the epigonadal adipose tissue of male wild-type and Bmal1  mice fed a normal rodent diet.(a) Bmal1, (b) Per2, (c) Pparγ, (d) Nr1d1, (e) Adipoq, (f) Lep (g) Retn, (h) Nampt (i) Adipor1 and (j) Adipor2. The data are the relative expression for each gene compared to Actin mRNA (mean ± s.e.m., n = 4 for each genotype), wild-type mice (open circles) and Bmal1  mice (closed circles). The highest expression of each gene for wild-type mice was set at one. The apparent absence of an SEM bar indicates that it is obscured by the symbol. The shaded areas represent the period of darkness.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3672145&req=5

pone-0065255-g005: The relative gene expression across 24 h of clock and other genes in the epigonadal adipose tissue of male wild-type and Bmal1 mice fed a normal rodent diet.(a) Bmal1, (b) Per2, (c) Pparγ, (d) Nr1d1, (e) Adipoq, (f) Lep (g) Retn, (h) Nampt (i) Adipor1 and (j) Adipor2. The data are the relative expression for each gene compared to Actin mRNA (mean ± s.e.m., n = 4 for each genotype), wild-type mice (open circles) and Bmal1 mice (closed circles). The highest expression of each gene for wild-type mice was set at one. The apparent absence of an SEM bar indicates that it is obscured by the symbol. The shaded areas represent the period of darkness.

Mentions: In the epigonadal fat, overall expression of Per2 (−30%), Pparγ (24%), Nr1d1 (−98%), Adipoq (−31%), Retn (−29%), Nampt (−52%), Adipor1 (−16%) and Adipor2 (−35%) mRNA was decreased (P<0.05), but Lep mRNA was unchanged (P>0.05) in male Bmal1 mice compared to the wild-type mice (Fig. 5). Expression of Bmal1, Per2, Pparγ, Nr1d1, Adipoq, Lep, Adipor1 and Adipor2 mRNA was rhythmic in wild-type mice (fitted significantly to a sine curve), but Retn and Nampt mRNA expression was arrhythmic. Expression of all genes analysed in male Bmal1 mice was arrhythmic except for Lep mRNA (P<0.05).


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)

The relative gene expression across 24 h of clock and other genes in the epigonadal adipose tissue of male wild-type and Bmal1  mice fed a normal rodent diet.(a) Bmal1, (b) Per2, (c) Pparγ, (d) Nr1d1, (e) Adipoq, (f) Lep (g) Retn, (h) Nampt (i) Adipor1 and (j) Adipor2. The data are the relative expression for each gene compared to Actin mRNA (mean ± s.e.m., n = 4 for each genotype), wild-type mice (open circles) and Bmal1  mice (closed circles). The highest expression of each gene for wild-type mice was set at one. The apparent absence of an SEM bar indicates that it is obscured by the symbol. The shaded areas represent the period of darkness.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065255-g005: The relative gene expression across 24 h of clock and other genes in the epigonadal adipose tissue of male wild-type and Bmal1 mice fed a normal rodent diet.(a) Bmal1, (b) Per2, (c) Pparγ, (d) Nr1d1, (e) Adipoq, (f) Lep (g) Retn, (h) Nampt (i) Adipor1 and (j) Adipor2. The data are the relative expression for each gene compared to Actin mRNA (mean ± s.e.m., n = 4 for each genotype), wild-type mice (open circles) and Bmal1 mice (closed circles). The highest expression of each gene for wild-type mice was set at one. The apparent absence of an SEM bar indicates that it is obscured by the symbol. The shaded areas represent the period of darkness.
Mentions: In the epigonadal fat, overall expression of Per2 (−30%), Pparγ (24%), Nr1d1 (−98%), Adipoq (−31%), Retn (−29%), Nampt (−52%), Adipor1 (−16%) and Adipor2 (−35%) mRNA was decreased (P<0.05), but Lep mRNA was unchanged (P>0.05) in male Bmal1 mice compared to the wild-type mice (Fig. 5). Expression of Bmal1, Per2, Pparγ, Nr1d1, Adipoq, Lep, Adipor1 and Adipor2 mRNA was rhythmic in wild-type mice (fitted significantly to a sine curve), but Retn and Nampt mRNA expression was arrhythmic. Expression of all genes analysed in male Bmal1 mice was arrhythmic except for Lep mRNA (P<0.05).

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