Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 2/2023

Open Access 27-09-2022 | Opioids | Original Article

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

Authors: Lihua Sun, Richard Aarnio, Erika Atencio Herre, Salli Kärnä, Senthil Palani, Helena Virtanen, Heidi Liljenbäck, Jenni Virta, Aake Honkaniemi, Vesa Oikonen, Chunlei Han, Sanna Laurila, Marco Bucci, Semi Helin, Emrah Yatkin, Lauri Nummenmaa, Pirjo Nuutila, Jing Tang, Anne Roivainen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2023

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference McElroy JF, Wade GN. Short photoperiod stimulates brown adipose tissue growth and thermogenesis but not norepinephrine turnover in Syrian hamsters. Physiol Behav. 1986;37:307–11.CrossRef McElroy JF, Wade GN. Short photoperiod stimulates brown adipose tissue growth and thermogenesis but not norepinephrine turnover in Syrian hamsters. Physiol Behav. 1986;37:307–11.CrossRef
2.
go back to reference Wiesinger H, Heldmaier G, Buchberger A. Effect of photoperiod and acclimation temperature on nonshivering thermogenesis and GDP-binding of brown fat mitochondria in the Djungarian hamster Phodopus s. sungorus. Pflügers Arch Eur J Physiol. 1989;413:667–72.CrossRef Wiesinger H, Heldmaier G, Buchberger A. Effect of photoperiod and acclimation temperature on nonshivering thermogenesis and GDP-binding of brown fat mitochondria in the Djungarian hamster Phodopus s. sungorus. Pflügers Arch Eur J Physiol. 1989;413:667–72.CrossRef
3.
go back to reference Au-Yong ITH, Thorn N, Ganatra R, Perkins AC, Symonds ME. Brown adipose tissue and seasonal variation in humans. Diabetes. 2009;58:2583–7.CrossRef Au-Yong ITH, Thorn N, Ganatra R, Perkins AC, Symonds ME. Brown adipose tissue and seasonal variation in humans. Diabetes. 2009;58:2583–7.CrossRef
4.
go back to reference Darcq E, Kieffer BL. Opioid receptors: drivers to addiction? Nat Rev Neurosci. 2018. p. 499–514. Darcq E, Kieffer BL. Opioid receptors: drivers to addiction? Nat Rev Neurosci. 2018. p. 499–514.
5.
go back to reference Nummenmaa L, Saanijoki T, Tuominen L, Hirvonen J, Tuulari JJ, Nuutila P, et al. μ-Opioid receptor system mediates reward processing in humans. Nat Commun. 2018;9:1500.CrossRef Nummenmaa L, Saanijoki T, Tuominen L, Hirvonen J, Tuulari JJ, Nuutila P, et al. μ-Opioid receptor system mediates reward processing in humans. Nat Commun. 2018;9:1500.CrossRef
6.
go back to reference Karlsson HK, Tuominen L, Tuulari JJ, Hirvonen J, Parkkola R, Helin S, et al. Obesity is associated with decreased µ-opioid but unaltered dopamine D2 receptor availability in the brain. J Neurosci. 2015;35:3959–65.CrossRef Karlsson HK, Tuominen L, Tuulari JJ, Hirvonen J, Parkkola R, Helin S, et al. Obesity is associated with decreased µ-opioid but unaltered dopamine D2 receptor availability in the brain. J Neurosci. 2015;35:3959–65.CrossRef
7.
go back to reference Tuulari JJ, Tuominen L, de Boer FE, Hirvonen J, Helin S, Nuutila P, et al. Feeding releases endogenous opioids in humans. J Neurosci. 2017;37:8284–91.CrossRef Tuulari JJ, Tuominen L, de Boer FE, Hirvonen J, Helin S, Nuutila P, et al. Feeding releases endogenous opioids in humans. J Neurosci. 2017;37:8284–91.CrossRef
8.
go back to reference Sun L, Tang J, Liljenbäck H, Honkaniemi A, Virta J, Isojärvi J, et al. Seasonal variation in brain mu-opioid receptor availability. J Neurosci. 2021;41:1265–73.CrossRef Sun L, Tang J, Liljenbäck H, Honkaniemi A, Virta J, Isojärvi J, et al. Seasonal variation in brain mu-opioid receptor availability. J Neurosci. 2021;41:1265–73.CrossRef
9.
go back to reference Stein C, Hassan AHS, Lehrberger K, Stein C, Giefing J, Yassouridis A. Local analgesic effect of endogenous opioid peptides. Lancet. 1993;342:321–4.CrossRef Stein C, Hassan AHS, Lehrberger K, Stein C, Giefing J, Yassouridis A. Local analgesic effect of endogenous opioid peptides. Lancet. 1993;342:321–4.CrossRef
10.
go back to reference Hassan AHS, Ableitner A, Stein C, Herz A. Inflammation of the rat paw enhances axonal transport of opioid receptors in the sciatic nerve and increases their density in the inflamed tissue. Neuroscience. 1993;55:185–95.CrossRef Hassan AHS, Ableitner A, Stein C, Herz A. Inflammation of the rat paw enhances axonal transport of opioid receptors in the sciatic nerve and increases their density in the inflamed tissue. Neuroscience. 1993;55:185–95.CrossRef
11.
go back to reference Stein C, Machelska H, Schäfer M. Peripheral analgesic and antiinflammatory effects of opioids. Z. Rheumatol. 2001. p. 416–24. Stein C, Machelska H, Schäfer M. Peripheral analgesic and antiinflammatory effects of opioids. Z. Rheumatol. 2001. p. 416–24.
12.
go back to reference Zhou L, Zhang Q, Stein C, Schäfer M. Contribution of opioid receptors on primary afferent versus sympathetic neurons to peripheral opioid analgesia. J Pharmacol Exp Ther. 1998;286:1000–6. Zhou L, Zhang Q, Stein C, Schäfer M. Contribution of opioid receptors on primary afferent versus sympathetic neurons to peripheral opioid analgesia. J Pharmacol Exp Ther. 1998;286:1000–6.
13.
go back to reference Grider JR, Makhlouf GM. Identification of opioid receptors on gastric muscle cells by selective receptor protection. Am J Physiol - Gastrointest Liver Physiol. 1991;260:G103–7.CrossRef Grider JR, Makhlouf GM. Identification of opioid receptors on gastric muscle cells by selective receptor protection. Am J Physiol - Gastrointest Liver Physiol. 1991;260:G103–7.CrossRef
14.
go back to reference Wittert G, Hope P, Pyle D. Tissue distribution of opioid receptor gene expression in the rat. Biochem Biophys Res Commun. 1996;218:877–81.CrossRef Wittert G, Hope P, Pyle D. Tissue distribution of opioid receptor gene expression in the rat. Biochem Biophys Res Commun. 1996;218:877–81.CrossRef
15.
16.
go back to reference Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes. 2010;34:S36-42.CrossRef Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes. 2010;34:S36-42.CrossRef
17.
go back to reference Cao WH, Morrison SF. Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia. Am J Physiol - Regul Integr Comp Physiol. 2005;288:723–32.CrossRef Cao WH, Morrison SF. Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia. Am J Physiol - Regul Integr Comp Physiol. 2005;288:723–32.CrossRef
18.
go back to reference Omran F, Christian M. Inflammatory signaling and brown fat activity. Front Endocrinol (Lausanne). 2020;11:156.CrossRef Omran F, Christian M. Inflammatory signaling and brown fat activity. Front Endocrinol (Lausanne). 2020;11:156.CrossRef
19.
go back to reference Hirvonen J, Aalto S, Hagelberg N, Maksimow A, Ingman K, Oikonen V, et al. Measurement of central μ-opioid receptor binding in vivo with PET and [11C]carfentanil: a test-retest study in healthy subjects. Eur J Nucl Med Mol Imaging. 2009;36:275–86.CrossRef Hirvonen J, Aalto S, Hagelberg N, Maksimow A, Ingman K, Oikonen V, et al. Measurement of central μ-opioid receptor binding in vivo with PET and [11C]carfentanil: a test-retest study in healthy subjects. Eur J Nucl Med Mol Imaging. 2009;36:275–86.CrossRef
20.
go back to reference Arvidsson U, Riedl M, Chakrabarti S, Lee JH, Nakano AH, Dado RJ, et al. Distribution and targeting of a μ-opioid receptor (MOR1) in brain and spinal cord. J Neurosci. 1995;15:3328–41.CrossRef Arvidsson U, Riedl M, Chakrabarti S, Lee JH, Nakano AH, Dado RJ, et al. Distribution and targeting of a μ-opioid receptor (MOR1) in brain and spinal cord. J Neurosci. 1995;15:3328–41.CrossRef
21.
go back to reference Laurila S, Sun L, Lahesmaa M, Schnabl K, Laitinen K, Klén R, et al. Secretin activates brown fat and induces satiation. Nat Metab. 2021;3:798–809.CrossRef Laurila S, Sun L, Lahesmaa M, Schnabl K, Laitinen K, Klén R, et al. Secretin activates brown fat and induces satiation. Nat Metab. 2021;3:798–809.CrossRef
22.
go back to reference Virtanen KA, Nuutila P. The importance of human brown adipose tissue volume. Nat Rev Endocrinol. 2021;17:453–4.CrossRef Virtanen KA, Nuutila P. The importance of human brown adipose tissue volume. Nat Rev Endocrinol. 2021;17:453–4.CrossRef
23.
go back to reference Li Y, Schnabl K, Gabler SM, Willershäuser M, Reber J, Karlas A, et al. Secretin-activated brown fat mediates prandial thermogenesis to induce satiation. Cell. 2018;175:1561-1574.e12.CrossRef Li Y, Schnabl K, Gabler SM, Willershäuser M, Reber J, Karlas A, et al. Secretin-activated brown fat mediates prandial thermogenesis to induce satiation. Cell. 2018;175:1561-1574.e12.CrossRef
24.
go back to reference Sternini C, Patierno S, Selmer IS, Kirchgessner A. The opioid system in the gastrointestinal tract. Neurogastroenterol. Motil. 2004. p. 3–16. Sternini C, Patierno S, Selmer IS, Kirchgessner A. The opioid system in the gastrointestinal tract. Neurogastroenterol. Motil. 2004. p. 3–16.
25.
go back to reference Janssen P, Pottel H, Vos R, Tack J. Endogenously released opioids mediate meal-induced gastric relaxation via peripheral mu-opioid receptors. Aliment Pharmacol Ther. 2011;33:607–14.CrossRef Janssen P, Pottel H, Vos R, Tack J. Endogenously released opioids mediate meal-induced gastric relaxation via peripheral mu-opioid receptors. Aliment Pharmacol Ther. 2011;33:607–14.CrossRef
26.
go back to reference Cao WH, Madden CJ, Morrison SF. Inhibition of brown adipose tissue thermogenesis by neurons in the ventrolateral medulla and in the nucleus tractus solitarius. Am J Physiol - Regul Integr Comp Physiol. 2010;299:277–90.CrossRef Cao WH, Madden CJ, Morrison SF. Inhibition of brown adipose tissue thermogenesis by neurons in the ventrolateral medulla and in the nucleus tractus solitarius. Am J Physiol - Regul Integr Comp Physiol. 2010;299:277–90.CrossRef
27.
go back to reference Berridge KC. “Liking” and “wanting” food rewards: brain substrates and roles in eating disorders. Physiol Behav. 2009;97:537–50.CrossRef Berridge KC. “Liking” and “wanting” food rewards: brain substrates and roles in eating disorders. Physiol Behav. 2009;97:537–50.CrossRef
28.
go back to reference Karlsson HK, Tuulari JJ, Tuominen L, Hirvonen J, Honka H, Parkkola R, et al. Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity. Mol Psychiatry. 2016;21:1057–62.CrossRef Karlsson HK, Tuulari JJ, Tuominen L, Hirvonen J, Honka H, Parkkola R, et al. Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity. Mol Psychiatry. 2016;21:1057–62.CrossRef
29.
go back to reference Sher L. Role of endogenous opioids in the effects of light on mood and behavior. Med Hypotheses. 2001;57:609–11.CrossRef Sher L. Role of endogenous opioids in the effects of light on mood and behavior. Med Hypotheses. 2001;57:609–11.CrossRef
30.
go back to reference Wintzen M, Yaar M, Burbach JPH, Gilchrest BA. Proopiomelanocortin gene product regulation in keratinocytes. J Invest Dermatol. 1996;106:673–8.CrossRef Wintzen M, Yaar M, Burbach JPH, Gilchrest BA. Proopiomelanocortin gene product regulation in keratinocytes. J Invest Dermatol. 1996;106:673–8.CrossRef
31.
go back to reference Kraus J, Börner C, Giannini E, Hickfang K, Braun H, Mayer P, et al. Regulation of μ-opioid receptor gene transcription by interleukin-4 and influence of an allelic variation within a STAT6 transcription factor binding site. J Biol Chem. 2001;276:43901–8.CrossRef Kraus J, Börner C, Giannini E, Hickfang K, Braun H, Mayer P, et al. Regulation of μ-opioid receptor gene transcription by interleukin-4 and influence of an allelic variation within a STAT6 transcription factor binding site. J Biol Chem. 2001;276:43901–8.CrossRef
Metadata
Title
[11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue
Authors
Lihua Sun
Richard Aarnio
Erika Atencio Herre
Salli Kärnä
Senthil Palani
Helena Virtanen
Heidi Liljenbäck
Jenni Virta
Aake Honkaniemi
Vesa Oikonen
Chunlei Han
Sanna Laurila
Marco Bucci
Semi Helin
Emrah Yatkin
Lauri Nummenmaa
Pirjo Nuutila
Jing Tang
Anne Roivainen
Publication date
27-09-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2023
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05969-5

Other articles of this Issue 2/2023

European Journal of Nuclear Medicine and Molecular Imaging 2/2023 Go to the issue