Divergent Roles of α5 and β4 Nicotinic Receptor Subunits in Food Reward and Nicotine-induced Weight Loss in Male Mice
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Divergent Roles of α5 and β4 Nicotinic Receptor Subunits in Food Reward and Nicotine-induced Weight Loss in Male Mice. / Breum, Alberte Wollesen; Falk, Sarah; Svendsen, Charlotte Sashi Aier; Nicolaisen, Trine Sand; Mathiesen, Cecilie Vad; Maskos, Uwe; Clemmensen, Christoffer.
In: Endocrinology, Vol. 163, No. 7, bqac079, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Divergent Roles of α5 and β4 Nicotinic Receptor Subunits in Food Reward and Nicotine-induced Weight Loss in Male Mice
AU - Breum, Alberte Wollesen
AU - Falk, Sarah
AU - Svendsen, Charlotte Sashi Aier
AU - Nicolaisen, Trine Sand
AU - Mathiesen, Cecilie Vad
AU - Maskos, Uwe
AU - Clemmensen, Christoffer
N1 - Publisher Copyright: © 2022 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2022
Y1 - 2022
N2 - A major obstacle to successful smoking cessation is the prospect of weight gain. Despite a clear relationship between cigarette smoking and body weight, surprisingly little is known about the physiological and molecular mechanism by which nicotine affects energy homeostasis and food-motivated behaviors. Here we use loss-of-function mouse models to demonstrate that 2 nicotinic acetylcholine receptor (nAChR) subunits encoded by the CHRNA5-CHRNA3-CHRNB4 gene cluster, α5 and β4, exhibit divergent roles in food reward. We also reveal that β4-containing nAChRs are essential for the weight-lowering effects of nicotine in diet-induced obese mice. Finally, our data support the notion of crosstalk between incretin biology and nAChR signaling, as we demonstrate that the glycemic benefits of glucagon-like peptide-1 receptor activation partially relies on β4-containing nAChRs. Together, these data encourage further research into the role of cholinergic neurotransmission in regulating food reward and the translational pursuit of site-directed targeting of β4-containing nAChRs for treatment of metabolic disease.
AB - A major obstacle to successful smoking cessation is the prospect of weight gain. Despite a clear relationship between cigarette smoking and body weight, surprisingly little is known about the physiological and molecular mechanism by which nicotine affects energy homeostasis and food-motivated behaviors. Here we use loss-of-function mouse models to demonstrate that 2 nicotinic acetylcholine receptor (nAChR) subunits encoded by the CHRNA5-CHRNA3-CHRNB4 gene cluster, α5 and β4, exhibit divergent roles in food reward. We also reveal that β4-containing nAChRs are essential for the weight-lowering effects of nicotine in diet-induced obese mice. Finally, our data support the notion of crosstalk between incretin biology and nAChR signaling, as we demonstrate that the glycemic benefits of glucagon-like peptide-1 receptor activation partially relies on β4-containing nAChRs. Together, these data encourage further research into the role of cholinergic neurotransmission in regulating food reward and the translational pursuit of site-directed targeting of β4-containing nAChRs for treatment of metabolic disease.
KW - body weight
KW - Metabolism
KW - nAChR
KW - Nicotine
KW - Nicotinic receptor
KW - Reward
U2 - 10.1210/endocr/bqac079
DO - 10.1210/endocr/bqac079
M3 - Journal article
C2 - 35595472
AN - SCOPUS:85133707093
VL - 163
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0013-7227
IS - 7
M1 - bqac079
ER -
ID: 314441432