Abstract

Insulin resistance is a main determinant in the development of type 2 diabetes mellitus and a major cause of morbidity and mortality. The circadian timing system consists of a central brain clock in the hypothalamic suprachiasmatic nucleus and various peripheral tissue clocks. The circadian timing system is responsible for the coordination of many daily processes, including the daily rhythm in human glucose metabolism. The central clock regulates food intake, energy expenditure and whole-body insulin sensitivity, and these actions are further fine-tuned by local peripheral clocks. For instance, the peripheral clock in the gut regulates glucose absorption, peripheral clocks in muscle, adipose tissue and liver regulate local insulin sensitivity, and the peripheral clock in the pancreas regulates insulin secretion. Misalignment between different components of the circadian timing system and daily rhythms of sleep–wake behaviour or food intake as a result of genetic, environmental or behavioural factors might be an important contributor to the development of insulin resistance. Specifically, clock gene mutations, exposure to artificial light–dark cycles, disturbed sleep, shift work and social jet lag are factors that might contribute to circadian disruption. Here, we review the physiological links between circadian clocks, glucose metabolism and insulin sensitivity, and present current evidence for a relationship between circadian disruption and insulin resistance. We conclude by proposing several strategies that aim to use chronobiological knowledge to improve human metabolic health.

Key points

• The circadian timing system consists of a central brain clock in the hypothalamic suprachiasmatic nucleus and peripheral clocks in tissues, including the liver, muscle, adipose tissue and pancreas.
• Misalignment between different components of the circadian timing system and daily rhythms of sleep–wake behaviour and food intake might contribute to the development of insulin resistance.
• Strategies to improve metabolic health by circadian synchrony include modulating light exposure, modulating rhythmic behaviour and chronotherapy.
• Circadian molecules are a promising new treatment option for insulin resistance.

https://www.nature.com/articles/s41574-018-0122-1

The post Circadian clocks and insulin resistance appeared first on EMFSA.

Abstract

The circadian clock exerts temporal coordination of metabolic pathways. Clock disruption is intimately linked with the development of obesity and insulin resistance, and our previous studies found that the essential clock transcription activator, Brain and Muscle Arnt-like 1 (Bmal1), is a key regulator of adipogenesis. However, the metabolic consequences of chronic shiftwork on adipose tissues have not been clearly defined. Here, using an environmental lighting-induced clock disruption that mimics rotating shiftwork schedule, we show that chronic clock dysregulation for 6 months in mice resulted in striking adipocyte hypertrophy with adipose tissue inflammation and fibrosis. Both visceral and subcutaneous depots display enlarged adipocyte with prominent crown-like structures indicative of macrophage infiltration together with evidence of extracellular matrix remodeling. Global transcriptomic analyses of these fat depots revealed that shiftwork resulted in up-regulations of inflammatory, adipogenic and angiogenic pathways with disruption of normal time-of-the-day-dependent regulation. These changes in adipose tissues are associated with impaired insulin signaling in mice subjected to shiftwork, together with suppression of the mTOR signaling pathway. Taken together, our study identified the significant adipose depot dysfunctions induced by chronic shiftwork regimen that may underlie the link between circadian misalignment and insulin resistance.

https://pubmed.ncbi.nlm.nih.gov/33285245/

The post Chronic circadian shift leads to adipose tissue inflammation and fibrosis appeared first on EMFSA.