Effects of Chronic Sleep Restriction on Transcriptional Sirtuin 1 Signaling Regulation in Male Mice White Adipose Tissue

TL;DR

This study shows how chronic sleep restriction affects fat tissue metabolism in mice through changes in specific genes.

Contribution

The study reveals novel molecular effects of chronic sleep restriction on white adipose tissue in mice.

Findings

Chronic sleep restriction upregulates SIRT-1 and genes related to lipid homeostasis and adipose development.

Transcription factors involved in fat cell development are downregulated in sleep-restricted mice.

SIRT1-dependent pathways may help prevent weight gain despite sleep loss.

Abstract

Chronic sleep restriction (CSR) is a prevalent issue in modern society that is associated with several pathological states, ranging from neuropsychiatric to metabolic diseases. Despite its known impact on metabolism, the specific effects of CSR on the molecular mechanisms involved in maintaining metabolic homeostasis at the level of white adipose tissue (WAT) remain poorly understood. Therefore, this study aimed to investigate the influence of CSR on sirtuin 1 (SIRT1) and the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway in the WAT of young male mice. Both genes interact with specific targets involved in multiple metabolic processes, including adipocyte differentiation, browning, and lipid metabolism. The quantitative PCR (qPCR) results demonstrated a significant upregulation of SIRT-1 and some of its target genes associated with the transcriptional regulation of lipid homeostasis (i.e., PPARα, PPARγ, PGC-1α, and SREBF) and adipose tissue development (i.e., leptin, adiponectin) in CSR mice. On the contrary, DNA-binding transcription factors (i.e., CEBP-β and C-myc), which play a pivotal function during the adipogenesis process, were found to be down-regulated. Our results also suggest that the induction of SIRT1-dependent molecular pathways prevents weight gain. Overall, these findings offer new, valuable insights into the molecular adaptations of WAT to CSR, in order to support increased energy demand due to sleep loss.

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