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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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The body composition of male and female wild-type and Bmal1  mice fed either normal rodent chow or a high fat diet (22% fat).The data are the means (grams or grams per 20 grams body weight ± s.e.m.; n = 13–19 mice per group). Body weight (a, b), epigonadal fat pad (c, d), retroperitoneal fat pad (e, f), testis/uterus (g, h) and kidney (i, j). Males (a, c, e, g, i); females (b, d, f, h, j). Bars above the histogram define the difference between the groups with significant difference set to P<0.0125.
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pone-0065255-g003: The body composition of male and female wild-type and Bmal1 mice fed either normal rodent chow or a high fat diet (22% fat).The data are the means (grams or grams per 20 grams body weight ± s.e.m.; n = 13–19 mice per group). Body weight (a, b), epigonadal fat pad (c, d), retroperitoneal fat pad (e, f), testis/uterus (g, h) and kidney (i, j). Males (a, c, e, g, i); females (b, d, f, h, j). Bars above the histogram define the difference between the groups with significant difference set to P<0.0125.

Mentions: Following five weeks on the control diet, body weight of the male Bmal1 mice were 14% lower than wild-type mice (P<0.005). On the high fat diet, male Bmal1 mice gained weight such that they were no longer lighter than wild type mice (Fig. 3). Wild type mice had increased epididymal and retroperitoneal fat pads when placed on a high fat diet (P<0.001), while in the Bmal1 mice only the epididymal fat pads were increased for animals on the high fat diet (P<0.001). Male Bmal1 mice had 58% and 52% more epigonadal fat and 182% and 64% more retroperitoneal fat per gram of body weight than wild-type mice maintained on the normal chow and high fat diet respectively (P<0.001). When the epigonadal and retroperitoneal fad pad weights were combined, male Bmal1 mice had 1.8 fold more fat than the wild-type mice on the chow diet and 1.5 fold more when on the high fat diet. Testes weight in male Bmal1 mice were reduced compared to the wild type mice only when maintained on the chow diet (P<0.001) and kidney weight in the Bmal1 males was reduced compared to wild type on both diets (P<0.01).


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 body composition of male and female wild-type and Bmal1  mice fed either normal rodent chow or a high fat diet (22% fat).The data are the means (grams or grams per 20 grams body weight ± s.e.m.; n = 13–19 mice per group). Body weight (a, b), epigonadal fat pad (c, d), retroperitoneal fat pad (e, f), testis/uterus (g, h) and kidney (i, j). Males (a, c, e, g, i); females (b, d, f, h, j). Bars above the histogram define the difference between the groups with significant difference set to P<0.0125.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065255-g003: The body composition of male and female wild-type and Bmal1 mice fed either normal rodent chow or a high fat diet (22% fat).The data are the means (grams or grams per 20 grams body weight ± s.e.m.; n = 13–19 mice per group). Body weight (a, b), epigonadal fat pad (c, d), retroperitoneal fat pad (e, f), testis/uterus (g, h) and kidney (i, j). Males (a, c, e, g, i); females (b, d, f, h, j). Bars above the histogram define the difference between the groups with significant difference set to P<0.0125.
Mentions: Following five weeks on the control diet, body weight of the male Bmal1 mice were 14% lower than wild-type mice (P<0.005). On the high fat diet, male Bmal1 mice gained weight such that they were no longer lighter than wild type mice (Fig. 3). Wild type mice had increased epididymal and retroperitoneal fat pads when placed on a high fat diet (P<0.001), while in the Bmal1 mice only the epididymal fat pads were increased for animals on the high fat diet (P<0.001). Male Bmal1 mice had 58% and 52% more epigonadal fat and 182% and 64% more retroperitoneal fat per gram of body weight than wild-type mice maintained on the normal chow and high fat diet respectively (P<0.001). When the epigonadal and retroperitoneal fad pad weights were combined, male Bmal1 mice had 1.8 fold more fat than the wild-type mice on the chow diet and 1.5 fold more when on the high fat diet. Testes weight in male Bmal1 mice were reduced compared to the wild type mice only when maintained on the chow diet (P<0.001) and kidney weight in the Bmal1 males was reduced compared to wild type on both diets (P<0.01).

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