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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

Advanced light shifts lead to histological and gene expression changes in BAT and WAT.BAT (A) mass, (B) mRNA expression and (C) histology (H&E staining) of advanced and control rats. (D) WAT mRNA gene expression. (* = p<0.05, n = 7–8).
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pone.0122570.g005: Advanced light shifts lead to histological and gene expression changes in BAT and WAT.BAT (A) mass, (B) mRNA expression and (C) histology (H&E staining) of advanced and control rats. (D) WAT mRNA gene expression. (* = p<0.05, n = 7–8).

Mentions: Although no differences were seen in WAT weight (advances: 3.3 +/- 0.29 g; control: 3.7 +/- 0.30 g), BAT mass was increased in the advanced group and histological examination showed an accumulation of lipids, indicating a brown-to-white transformation similar to that found in obesity (Fig. 5A and C). No histological changes were seen in any other tissue analysed (S2 Fig.). Accordingly, the uncoupling protein 1 (Ucp-1) gene, which is a BAT marker of thermogenesis, decreased its expression by 40% (p = 0.041) (Fig. 5B). Furthermore, Cpt1B (p = 0.038) and Pparα (p = 0.003) were also downregulated in the advanced group (Fig. 5B), indicating that lipid metabolism is not activated in BAT of advanced rats.


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)

Advanced light shifts lead to histological and gene expression changes in BAT and WAT.BAT (A) mass, (B) mRNA expression and (C) histology (H&E staining) of advanced and control rats. (D) WAT mRNA gene expression. (* = p<0.05, n = 7–8).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122570.g005: Advanced light shifts lead to histological and gene expression changes in BAT and WAT.BAT (A) mass, (B) mRNA expression and (C) histology (H&E staining) of advanced and control rats. (D) WAT mRNA gene expression. (* = p<0.05, n = 7–8).
Mentions: Although no differences were seen in WAT weight (advances: 3.3 +/- 0.29 g; control: 3.7 +/- 0.30 g), BAT mass was increased in the advanced group and histological examination showed an accumulation of lipids, indicating a brown-to-white transformation similar to that found in obesity (Fig. 5A and C). No histological changes were seen in any other tissue analysed (S2 Fig.). Accordingly, the uncoupling protein 1 (Ucp-1) gene, which is a BAT marker of thermogenesis, decreased its expression by 40% (p = 0.041) (Fig. 5B). Furthermore, Cpt1B (p = 0.038) and Pparα (p = 0.003) were also downregulated in the advanced group (Fig. 5B), indicating that lipid metabolism is not activated in BAT of advanced rats.

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