Rodent Models for the Analysis of Tissue Clock Function in Metabolic Rhythms Research.

Anthony H Tsang,Brinja Leinweber,Mariana Astiz,Henrik Oster

doi:10.3389/fendo.2017.00027

Anthony H Tsang, Brinja Leinweber + Show 2 more

Open Access

https://doi.org/10.3389/fendo.2017.00027

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Abstract

The circadian timing system consists on a distributed network of cellular clocks that together coordinate 24-h rhythms of physiology and behavior. Clock function and metabolism are tightly coupled, from the cellular to the organismal level. Genetic and non-genetic approaches in rodents have been employed to study circadian clock function in the living organism. Due to the ubiquitous expression of clock genes and the intricate interaction between the circadian system and energy metabolism, genetic approaches targeting specific tissue clocks have been used to assess their contribution in systemic metabolic processes. However, special requirements regarding specificity and efficiency have to be met to allow for valid conclusions from such studies. In this review, we provide a brief summary of different approaches developed for dissecting tissue clock function in the metabolic context in rodents, compare their strengths and weaknesses, and suggest new strategies in assessing tissue clock output and the consequences of circadian clock disruption in vivo.

Highlights

A network of cellular clocks adapts physiology and behavior to a 24-h rhythmic environment
Approaches describing the interplay between circadian clock function and metabolism were based on models of non-genetic circadian disruption (Table 1)
Administration of REV-ERB agonists in mice induces body weight loss and decreased lipogenesis in liver and white adipose tissue, increased lipid and glucose oxidation in skeletal muscle, and elevated energy expenditure [42]. These studies provide evidence that the circadian clock plays a fundamental role in energy homeostasis and that different clock components have specific functions in this context

Summary

INTRODUCTION

A network of cellular clocks adapts physiology and behavior to a 24-h rhythmic environment. Administration of REV-ERB agonists in mice induces body weight loss and decreased lipogenesis in liver and white adipose tissue, increased lipid and glucose oxidation in skeletal muscle, and elevated energy expenditure [42] Together, these studies provide evidence that the circadian clock plays a fundamental role in energy homeostasis and that different clock components have specific functions in this context. Because the mice used in these studies carry clock gene mutations in all tissues including the SCN, much like the non-genetic models discussed above, metabolic phenotypes may be confounded by systemic abnormalities such as altered sleep patterns, activity and feeding behaviors, or counteractive consequences of clock disruption in different tissues. Conclusions drawn from these experiments are often confounded by intrinsic drawbacks of the classical CRE-loxP system which novel genetic tools may help to overcome

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CONCLUSION