Secretin activates brown fat and induces satiation

Laurila, Sanna; Sun, Lihua; Lahesmaa, Minna; Schnabl, Katharina; Laitinen, Kirsi; Клен, Рику; Li, Yongguo; Baláž, Miroslav; Wolfrum, Christian; Steiger, Katja; Niemi, Tarja; Taittonen, Markku; U-Din, Mueez; Välikangas, Tommi; Elo, Laura L.; Eskola, Olli; Kirjavainen, Anna; Nummenmaa, Lauri; Virtanen, Kirsi A.; Klingenspor, Martin; Nuutila, Pirjo

doi:10.1038/s42255-021-00409-4

Cited by 49 publications

(76 citation statements)

References 56 publications

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“…We have recently conducted a study where secretin’s effects were investigated with whole body [ 18 F]-FDG-PET, to measure glucose uptake rates, and [ 15 O]-H 2 O-PET, to measure BAT perfusion. In accordance with our previous findings in mice, we showed that secretin activates BAT in healthy lean men ( 13 ). More specifically, secretin induced an increase in [ 18 F]-FDG uptake in BAT, suggestive of increased metabolic activity, while perfusion was not changed in an acute setting ( 13 ).…”

Section: Recent Pet and Fmri Datasupporting

confidence: 93%

“…In accordance with our previous findings in mice, we showed that secretin activates BAT in healthy lean men ( 13 ). More specifically, secretin induced an increase in [ 18 F]-FDG uptake in BAT, suggestive of increased metabolic activity, while perfusion was not changed in an acute setting ( 13 ). In mice, maximal thermogenesis was achieved 20 minutes after secretin administration ( 12 ).…”

Section: Recent Pet and Fmri Datasupporting

confidence: 93%

“…The [ 18 F]-FDG scan was initiated 20 minutes after the first 1 IU/kg injection of secretin, simultaneously with another 1 IU/kg 2-minute infusion of secretin. In contrast, perfusion was measured only two minutes after the first secretin infusion ( 13 ). Since secretin stimulates BAT endogenously instead of through a faster neuronally mediated effect, the perfusion scan was likely conducted too early to measure secretin’s effect on BAT perfusion.…”

Section: Recent Pet and Fmri Datamentioning

confidence: 99%

“…Evidence of a catabolic effect was found with indirect calorimetry: whole body energy expenditure increased by secretin compared to placebo ( 13 ). BAT computer tomography radiodensity was increased at the end of the scan, compared to the start, and this increase was associated with whole body fat oxidation after secretin infusion ( 13 ).…”

Section: Recent Pet and Fmri Datamentioning

confidence: 99%

“…It is a powerful lipolytic agent and its levels are increased after prolonged fasting ( 11 ). Moreover, preclinical and clinical studies have recently shown that secretin may induce satiation ( 12 , 13 ). Also following bariatric surgery, secretin levels have shown to be increased ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

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Pleiotropic Effects of Secretin: A Potential Drug Candidate in the Treatment of Obesity?

et al. 2021

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Secretin is the first hormone that has been discovered, inaugurating the era and the field of endocrinology. Despite the initial focus, the interest in its actions faded away over the decades. However, there is mounting evidence regarding the pleiotropic beneficial effects of secretin on whole-body homeostasis. In this review, we discuss the evidence from preclinical and clinical studies based on which secretin may have a role in the treatment of obesity.

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Section: Recent Pet and Fmri Datasupporting

confidence: 93%

Section: Recent Pet and Fmri Datasupporting

confidence: 93%

Section: Recent Pet and Fmri Datamentioning

confidence: 99%

Section: Recent Pet and Fmri Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pleiotropic Effects of Secretin: A Potential Drug Candidate in the Treatment of Obesity?

et al. 2021

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[11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue

Sun

Aarnio

Herre

et al. 2022

Eur J Nucl Med Mol Imaging

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Purpose Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signaling regulates BAT thermogenesis, and that the expression of the brain mu-opioid receptor (MOR) varies seasonally. Therefore, it is important to know whether MOR expression in BAT shows seasonal variation. Methods We determined the effect of photoperiod on BAT MOR availability using [11C]carfentanil positron emission tomography (PET). Adult rats (n = 9) were repeatedly imaged under various photoperiods in order to simulate seasonal changes. Results Long photoperiod was associated with low MOR expression in BAT (β = − 0.04, 95% confidence interval: − 0.07, − 0.01), but not in muscles. We confirmed the expression of MOR in BAT and muscle using immunofluorescence staining. Conclusion Photoperiod affects MOR availability in BAT. Sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. The present study supports the utility of [11C]carfentanil PET to study the peripheral MOR system.

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Secretin modulates appetite via brown adipose tissue-brain axis

Sun

Laurila

Lahesmaa

et al. 2023

Eur J Nucl Med Mol Imaging

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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.

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Secretin activates brown fat and induces satiation

Cited by 49 publications

References 56 publications

Pleiotropic Effects of Secretin: A Potential Drug Candidate in the Treatment of Obesity?

Pleiotropic Effects of Secretin: A Potential Drug Candidate in the Treatment of Obesity?

[11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue

Secretin modulates appetite via brown adipose tissue-brain axis

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