Intact innervation is essential for diet-induced recruitment of brown adipose tissue.

Alexander W Fischer,Jan Nedergaard,Joerg Heeren,Christian Schlein,Barbara Cannon

doi:10.1152/ajpendo.00443.2018

Abstract

The possibility that recruitment and activation of brown adipose tissue (BAT) thermogenesis could be beneficial for curtailing obesity development in humans prompts a need for a better understanding of the control of these processes [that are often referred to collectively as diet-induced thermogenesis (DIT)]. Dietary conditions are associated with large changes in blood-borne factors that could be responsible for BAT recruitment, but BAT is also innervated by the sympathetic nervous system. To examine the significance of the innervation for DIT recruitment, we surgically denervated the largest BAT depot, i.e., the interscapular BAT depot in mice and exposed the mice at thermoneutrality to a high-fat diet versus a chow diet. Denervation led to an alteration in feeding pattern but did not lead to enhanced obesity, but obesity was achieved with a lower food intake, as denervation increased metabolic efficiency. Conclusively, denervation totally abolished the diet-induced increase in total UCP1 protein levels observed in the intact mice, whereas basal UCP1 expression was not dependent on innervation. The denervation of interscapular BAT did not discernably hyper-recruit other BAT depots, and no UCP1 protein could be detected in the principally browning-competent inguinal white adipose tissue depot under any of the examined conditions. We conclude that intact innervation is essential for diet-induced thermogenesis and that circulating factors cannot by themselves initiate recruitment of brown adipose tissue under obesogenic conditions. Therefore, the processes that link food intake and energy storage to activation of the nervous system are those of significance for the further understanding of diet-induced thermogenesis.

Highlights

An important incentive for the present interest in brown adipose tissue as such, and in white adipose tissue browning as well, is undoubtedly the expectation that recruitment and activation of the thermogenic potential of these tissues could* J
We found that the procedure was successful in bringing about localized sympathectomy in that tyrosine hydroxylase was eliminated to 95% from the interscapular depot (Fig. 5C), whereas the tyrosine hydroxylase was fully preserved in a nondenervated brown adipose tissue (BAT) depot (Fig. 7A) and in inguinal white adipose tissue (ingWAT) (Fig. 8A)
We demonstrate that the increase in thermogenic capacity observed under conditions of chronic overeating and obesity is fully dependent on innervation of the brown adipose tissue depots

Summary

Introduction

An important incentive for the present interest in brown adipose tissue as such, and in white adipose tissue browning as well, is undoubtedly the expectation that recruitment and activation of the thermogenic potential of these tissues could* J. An important incentive for the present interest in brown adipose tissue as such, and in white adipose tissue browning as well, is undoubtedly the expectation that recruitment and activation of the thermogenic potential of these tissues could. Nedergaard are co-senior authors of this work. It is of considerable interest to understand the physiological pathways that augment the recruitment processes in these tissues when individuals are exposed to obesogenic conditions. Such pathways could be of hormonal nature, i.e., food-related, blood-borne substances that would directly interact with the tissues - or they could be mediated via the innervation of the tissues

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