Date Published: March 1, 2019
Publisher: American Physiological Society
Author(s): Alexander W. Fischer, Christian Schlein, Barbara Cannon, Joerg Heeren, Jan Nedergaard.
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.
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 help in curbing the increase in obesity presently encountered worldwide. Therefore, 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.
In the present study, we have examined the functional significance of the innervation of BAT for the adaptive response to overfeeding referred to as diet-induced thermogenesis (DIT). We used classical bilateral nerve sectioning of the interscapular depot and found that innervation was absolutely essential for the diet-induced recruitment of BAT under conditions of thermoneutrality. However, basal UCP1 levels were almost fully maintained even in the absence of innervation, and notably, other brown and white adipose depots did not markedly hyper-recruit to compensate for the absence of the activation of the interscapular depot. Several systemic effects caused by the denervation were also observed.
This study was supported by grants from the Swedish Research Council, the German Research Council (DFG-HE3645/7-1), and the Studienstiftung des deutschen Volkes.
No conflicts of interest, financial or otherwise, are declared by the authors.
J.N. conceived and designed research; A.W.F. and C.S. performed experiments; A.W.F., C.S., and J.N. analyzed data; A.W.F., C.S., B.C., J.H., and J.N. interpreted results of experiments; A.W.F. prepared figures; A.W.F. drafted manuscript; A.W.F., B.C., J.H., and J.N. edited and revised manuscript; A.W.F., C.S., B.C., J.H., and J.N. approved final version of manuscript.