Evidence for the role of β2* nAChR desensitization in regulating body weight in obese mice

Dezfuli, Ghazaul; Kellar, Kenneth J.; Dretchen, Kenneth L.; Tizabi, Yousef; Sahibzada, Niaz; Gillis, Richard A.

doi:10.1016/j.neuropharm.2016.07.020

Cited by 10 publications

(5 citation statements)

References 30 publications

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“…This finding substantiates previous work focusing on β4 knockdown in the ARC ( 14 , 32 ). α7- and β2-nAChRs have been implicated previously in homeostatic food intake regulation ( 47–49 ), and here we show a role for α5 and β4 subunits in food reward. However, in terms of pharmacological nicotine, the effects on weight loss appear to be exclusively governed by β4-nAChRs.…”

Section: Discussionsupporting

confidence: 77%

Divergent Roles of α5 and β4 Nicotinic Receptor Subunits in Food Reward and Nicotine-induced Weight Loss in Male Mice

et al. 2022

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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.

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Section: Discussionsupporting

confidence: 77%

Divergent Roles of α5 and β4 Nicotinic Receptor Subunits in Food Reward and Nicotine-induced Weight Loss in Male Mice

et al. 2022

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“…For example, an agonist at the alpha-7 nAChR subtype (TC-7020) has been shown to reduce weight gain and food intake in a mouse model of Type II Diabetes ( [38]; for a comprehensive review of the role of α7 receptors on food intake behaviors, see McFadden et al 2014). Similarly, the β2 agonist sazetidine-A and cytisine, a β4 agonist and partial β2 agonist, have also been shown to reduce food intake and body weight [26,42,43]. The MTAs, which interact with the nAChRs with varying potencies and binding affinities, represent a logical next step in understanding the role of nAChRs in modulating changes in energy balance and in the discovery of novel pharmacotherapies for the treatment of obesity.…”

Section: Introductionmentioning

confidence: 99%

Anatabine, Nornicotine, and Anabasine Reduce Weight Gain and Body Fat through Decreases in Food Intake and Increases in Physical Activity

Grebenstein

Erickson

Grace

et al. 2022

JCM

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Obesity is a leading cause of preventable death in the United States. Currently approved pharmacotherapies for the treatment of obesity are associated with rebound weight gain, negative side effects, and the potential for abuse. There is a need for new treatments with fewer side effects. Minor tobacco alkaloids (MTAs) are potential candidates for novel obesity pharmacotherapies. These alkaloids are structurally related to nicotine, which can help reduce body weight, but without the same addictive potential. The purpose of the current study was to examine the effects of three MTAs (nornicotine, anatabine, and anabasine) and nicotine on weight gain, body composition, chow intake, and physical activity. We hypothesized that the MTAs and nicotine would reduce weight gain through reductions in chow intake and increases in physical activity. To test this, male Sprague Dawley rats were housed in metabolic phenotyping chambers. Following acclimation to these chambers and to (subcutaneous (sc)) injections of saline, animals received daily injections (sc) of nornicotine, anabasine, anatabine, or nicotine for one week. Compared to saline-injected animals that gained body weight and body fat during the treatment phase, injections of nornicotine and anatabine prevented additional weight gain, alongside reductions in body fat. Rats receiving anabasine and nicotine gained body weight at a slower rate relative to rats receiving saline injections, and body fat remained unchanged. All compounds reduced the intake of chow pellets. Nornicotine and nicotine produced consistent increases in physical activity 6 h post-injection, whereas anabasine’s and anatabine’s effects on physical activity were more transient. These results show that short-term, daily administration of nornicotine, anabasine, and anatabine has positive effects on weight loss, through reductions in body fat and food intake and increases in physical activity. Together, these findings suggest that MTAs are worthy of further investigations as anti-obesity pharmacotherapies.

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“…The ablation of cholinergic neurons in the basal forebrain leads to hyperphagia and severe obesity in mice [15], whereas α7nAChR activation in a mouse model of diabetes improves metabolic parameters by reducing food intake [16]. Furthermore, studies show that the activation and inhibition of nicotinic receptors can modulate neuronal excitability in POMC and NPY neurons [17,18].…”

Section: Introductionmentioning

confidence: 99%

JAK2/STAT3 Pathway is Required for α7nAChR-Dependent Expression of POMC and AGRP Neuropeptides in Male Mice

Souza

Amaral

Souza

et al. 2019

Cell Physiol Biochem

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Evidence for the role of β2* nAChR desensitization in regulating body weight in obese mice

Cited by 10 publications

References 30 publications

Divergent Roles of α5 and β4 Nicotinic Receptor Subunits in Food Reward and Nicotine-induced Weight Loss in Male Mice

Divergent Roles of α5 and β4 Nicotinic Receptor Subunits in Food Reward and Nicotine-induced Weight Loss in Male Mice

Anatabine, Nornicotine, and Anabasine Reduce Weight Gain and Body Fat through Decreases in Food Intake and Increases in Physical Activity

JAK2/STAT3 Pathway is Required for α7nAChR-Dependent Expression of POMC and AGRP Neuropeptides in Male Mice

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