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

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.

Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

“…Currently, an ablation of nerve bundles of bilateral BAT was used to abolish the function of BAT in vivo. In consistence with previous studies (48,49,61), the surgical denervation was confirmed by the significant elimination of TH in BAT in the current study. We found that whitening occurred in denervated of BAT as evidenced by the uniocular morphology and decreased levels of UCP1 protein.…”

“…A recent study has reported that bilateral denervation of BAT can promote sWAT browning at thermoneutrality (48). However, A more recent study showed that no browning of sWAT was detectable in BAT-denervated mice (61). Similarly, in BATdenervated and BAT-removal mice at room temperature, we did not achieve significant evidence for browning of sWAT.…”

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

“…Different stimuli, like, e.g., abovementioned exposure to cold, lead to increased noradrenaline release and subsequent stimulation of various subtypes of β-adrenergic receptors (ADRBs), leading to the proliferation of brown adipocytes and activation of lipolysis and/or of thermogenesis. ADRB3 is the primary receptor involved in pathways related to adaptive thermogenesis in brown or beige adipocytes [ 34 ].…”

Combating Obesity With Thermogenic Fat: Current Challenges and Advancements

“…However, during disease states such as obesity, BMI can be above 30 kg/m 2 . WAT serves as the main energy store for the body, while brown adipose tissue (BAT) dissipates energy into heat via non-shivering thermogenesis (6)(7)(8).…”