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Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

Herrero L, Valcarcel L, da Silva CA, Albert N, Diez-Noguera A, Cambras T, Serra D - PLoS ONE (2015)

Bottom Line: However, the effect of phase shifts on metabolism is not completely understood.WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression.Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Facultat de Farmàcia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.

ABSTRACT
The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT), brown adipose tissue (BAT) and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level.

No MeSH data available.


Related in: MedlinePlus

Lighting and motor activity patterns.Top: Double plotted graphs corresponding to light patterns, where the dark areas correspond to darkness. Bottom: Motor activity of a representative animal of each group.
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pone.0122570.g001: Lighting and motor activity patterns.Top: Double plotted graphs corresponding to light patterns, where the dark areas correspond to darkness. Bottom: Motor activity of a representative animal of each group.

Mentions: To compare the global rhythmic pattern of each animal, we analysed periodograms for the same data set. Results show that motor activity patterns of the rats differed according to lighting conditions (Fig. 1). As expected [13], the motor activity rhythm of the advanced group was the most disturbed by the phase shifts. Both control and delayed groups showed a well-defined circadian rhythm, with periods of 24h and 24h 70 min, respectively, which explain 25% (SEM 1.3) of the variance of the data series. In the advanced group, chronic phase shifting was indicated by the presence of two simultaneous rhythms with different period: one whose period equals that of the light pattern (22h 50 minutes) and explained 7.7% (SEM 1.2) of the variance, and a free running rhythm with a period of 25h 8 min (SEM 4.3 min) that explained 5.48% (SEM 0.6%) of the variance. Similarly in the case of advanced and delayed group, all the animals showed a rhythm of 24h, which explained 14.6% of the variance (SEM 1.3) and in addition, 7 out of 8 rats showed a significant rhythm with a mean value of 25h 4min (SEM 2.23), not driven by light, which explained 4.63% (SEM 0.4) of the variance and can be considered the consequence of the masking effects of the phase shifts. The percentage of variance explained by the light-dependent rhythm differed among the groups, suggesting different importance of this rhythm on the animal behaviour: ANOVA and posthoc tests indicate that the PV of the advance group was lower than that of advances and delays group (p<0.05), delays group (p<0.001) and controls (p<0.001) and that the PV of advances and delays group was also lower than delay and control groups (p<0.05 in both cases).


Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

Herrero L, Valcarcel L, da Silva CA, Albert N, Diez-Noguera A, Cambras T, Serra D - PLoS ONE (2015)

Lighting and motor activity patterns.Top: Double plotted graphs corresponding to light patterns, where the dark areas correspond to darkness. Bottom: Motor activity of a representative animal of each group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383616&req=5

pone.0122570.g001: Lighting and motor activity patterns.Top: Double plotted graphs corresponding to light patterns, where the dark areas correspond to darkness. Bottom: Motor activity of a representative animal of each group.
Mentions: To compare the global rhythmic pattern of each animal, we analysed periodograms for the same data set. Results show that motor activity patterns of the rats differed according to lighting conditions (Fig. 1). As expected [13], the motor activity rhythm of the advanced group was the most disturbed by the phase shifts. Both control and delayed groups showed a well-defined circadian rhythm, with periods of 24h and 24h 70 min, respectively, which explain 25% (SEM 1.3) of the variance of the data series. In the advanced group, chronic phase shifting was indicated by the presence of two simultaneous rhythms with different period: one whose period equals that of the light pattern (22h 50 minutes) and explained 7.7% (SEM 1.2) of the variance, and a free running rhythm with a period of 25h 8 min (SEM 4.3 min) that explained 5.48% (SEM 0.6%) of the variance. Similarly in the case of advanced and delayed group, all the animals showed a rhythm of 24h, which explained 14.6% of the variance (SEM 1.3) and in addition, 7 out of 8 rats showed a significant rhythm with a mean value of 25h 4min (SEM 2.23), not driven by light, which explained 4.63% (SEM 0.4) of the variance and can be considered the consequence of the masking effects of the phase shifts. The percentage of variance explained by the light-dependent rhythm differed among the groups, suggesting different importance of this rhythm on the animal behaviour: ANOVA and posthoc tests indicate that the PV of the advance group was lower than that of advances and delays group (p<0.05), delays group (p<0.001) and controls (p<0.001) and that the PV of advances and delays group was also lower than delay and control groups (p<0.05 in both cases).

Bottom Line: However, the effect of phase shifts on metabolism is not completely understood.WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression.Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Facultat de Farmàcia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.

ABSTRACT
The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT), brown adipose tissue (BAT) and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level.

No MeSH data available.


Related in: MedlinePlus