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

PLoS One. 2015 Apr 2;10(4):e0122570. doi: 10.1371/journal.pone.0122570. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / metabolism
  • Animals
  • Body Weight
  • Circadian Rhythm / genetics*
  • Circadian Rhythm / physiology
  • Circadian Rhythm / radiation effects*
  • Endoplasmic Reticulum Stress / genetics
  • Endoplasmic Reticulum Stress / radiation effects
  • Gene Expression / radiation effects
  • Genetic Predisposition to Disease
  • Glucose / metabolism
  • Hypothalamus / metabolism
  • Light
  • Lipid Metabolism / genetics
  • Liver / metabolism
  • Male
  • Motor Activity
  • Neuropeptides / genetics
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / metabolism
  • Photoperiod*
  • Rats
  • Rats, Wistar
  • Transcriptome

Substances

  • Neuropeptides
  • Glucose

Grants and funding

This study was supported by the Spanish Ministry of Economy and Competitiveness (Grant BFU2008-00199 to TC and AD, Grant SAF2013-45887-R to LH and Grant SAF2011-30520-C02-01 to DS), Generalitat de Catalunya (2014SGR-465 to DS), Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III (Grant CB06/03/0026 to DS), European Foundation for the Study of Diabetes (EFSD)/Lilly and European Foundation for the Study of Diabetes (EFSD)/Janssen (research fellowships to LH), L’Oréal-UNESCO (research fellowship to LH) and by the Ministerio de Educación y Ciencia (BFU2008-00199). CAS was Bolsista da CAPES – Proc. nº BEX 4970/10-1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.