Laurila, S. | Search bioRxiv

bioRxiv2022

Secretin modulates appetite via brown adipose tissue - brain axis

Secretin activates brown adipose tissue (BAT) and induces satiation in both mice and humans. However, the exact brain mechanism of this satiety inducing, secretin-mediated gut-BAT-brain axis is unknown. In this placebo-controlled, single-blinded neuroimaging study, firstly using [18F]FDG-PET measures (n = 15), we established that secretin modulated brain glucose consumption through the BAT-brain axis. Predominantly, we found that BAT and caudate glucose uptake levels were negatively correlated (r = -0.54, p = 0.037) during secretin but not placebo condition. Then, using functional magnetic resonance imaging (fMRI; n = 14), we found that secretin down-regulated the brain response to appetizing food images and improved inhibitory control. Finally, in a PET-fMRI fusion analysis (n = 10), we disclosed the patterned correspondence between caudate glucose uptake and neuroactivity to reward and inhibition, showing that the secretin-induced neurometabolic coupling pattern promoted satiation. These findings suggest that secretin modulates the BAT-brain metabolic crosstalk and subsequent neurometabolic coupling to induce satiation, bearing potential clinical benefits for treating eating disorders. Significance of the studySecretin activates brown adipose tissue and induces satiation, but the underlying brain mechanisms are still unclear. This placebo-controlled PET-fMRI study uses brain metabolic and BOLD measures to dissect the modulatory effects of secretin on brain functions associative to satiation. Findings show that secretin i) modulates caudate glucose metabolism via the BAT-brain axis, ii) enhances BOLD response in inhibitory control, and iii) reduces reward-related BOLD response. Further evidence shows that these measured effects are tightly linked via the secretin-mediated brain neurometabolic coupling. This study significantly advances our knowledge on how secretin leads to satiation and highlights the potential role of secretin in treating eating disorders and obesity.

neuroscience↗

bioRxiv2022

Photoperiod modulates mu-opioid receptor availability in brown adipose tissue

Photoperiod drives metabolic activity of brown adipose tissue (BAT), and affects food intake and weight gain in mammals. Sympathetic innervation in BAT controls thermogenesis and facilitates physiological adaption to seasons, but the exact mechanism remains elusive. Previous studies show that the central opioid signaling tunes BAT heating and the brain muopioid receptor (MOR) levels have seasonal patterns. It is hence intriguing to know whether the peripheral MOR signaling shows seasonal variation. Here, we examined the effect of photoperiod on BAT MOR availability using [11C]carfentanil positron emission topography (PET). Adult rats (n = 9) were repeatedly imaged under changing photoperiods which simulates the local seasons. Long photoperiod downregulated MOR availability in BAT, while MOR availability in the muscles was unaffected. We confirmed the expression of MOR in BAT and muscle using immunofluorescence imaging. We conclude that photoperiod causally affects MOR availability in BAT, and sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. Significance of the studyPhotoperiod impacts the metabolic activity of brown adipose tissue (BAT) with the exact mechanism still unclear. The current study shows that photoperiod causally affects the mu-opioid receptor (MOR) levels in BAT, with longer photoperiod leading to lower MOR availability. This possibly indicates down-regulated innervation during bright seasons. Immunofluorescence staining data reveal expression of MOR in both brain and peripheral tissues, drawing attention to the under-investigated peripheral MOR system. Also, the study highlights the feasibility of [11C]carfentanil PET in studying the peripheral MOR signaling.

molecular biology↗