Secretin modulates appetite via brown adipose tissue-brain axis

Abstract

Purpose 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 largely unknown. Methods and results In this placebo-controlled, single-blinded neuroimaging study, firstly using [18F]-fluorodeoxyglucose (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 improved inhibitory control and downregulated the brain response to appetizing food images. 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 patterns promoted satiation. Conclusion These findings suggest that secretin may modulate the BAT-brain metabolic crosstalk and subsequently the neurometabolic coupling to induce satiation. The study advances our understanding of the secretin signaling in motivated eating behavior and highlights the potential role of secretin in treating eating disorders and obesity. Trial registration EudraCT no. 2016-002373-35, registered 2 June 2016; Clinical Trials no. NCT03290846, registered 25 September 2017.

Seasonal variation in D2/3 dopamine receptor availability in the human brain

“…The striatum is a brain key node for reward responses (Balleine et al, 2007) and energy consumption in the caudate may directly code the feeling of satiation or hunger (Sun et al, 2023). Given the role of striatal dopamine signaling in feeding behavior, enhanced D2R signaling in dark seasons may induce overeating (Shahar et al, 1999).…”

Brown adipocyte and browning thermogenesis: metabolic crosstalk beyond mitochondrial limits and physiological impacts

“…After meal, the rise in plasma secretin levels activated thermogenesis in BAT via lipolysis, and promoted satiety to reduce food intake, which may act via heat sensing in the brain to stimulate the feeling of satiety at least in mice [ 121 ]. In human, prandial BAT thermogenesis was also observed in human together with increased glucose uptake, and negatively correlated with caudate glucose uptake and inhibitory response, which led to increased satiety in human, suggesting a BAT-brain axis [ 122 , 123 ]. Future research is warranted to explore the molecular mechanisms underlying BAT-brain axis as well as their effects on whole body energy expenditure.…”