Nicotine administration decreases neuropeptide Y expression and increases leptin receptor expression in the hypothalamus of food-deprived rats

doi:10.1016/S0006-8993(02)04122-7

Brain Research

Volume 964, Issue 2, 28 February 2003, Pages 311-315

https://doi.org/10.1016/S0006-8993(02)04122-7 Get rights and content

Abstract

The effects of nicotine on the expressions of neuropeptide Y (NPY) and leptin receptor in the rat hypothalamus were investigated via immunohistochemistry. The results show that NPY expression is not affected in the arcuate nucleus (ARN) and is increased only slightly in the paraventricular nucleus (PVN) by nicotine administration under normal (i.e. fed) conditions and that leptin receptor expression is decreased slightly in the ARN and not affected in the PVN following nicotine treatment under the same conditions. Food deprivation enhanced NPY and suppressed leptin receptor expression in the ARN and PVN of the hypothalamus. Nicotine administration resulted in decreased NPY and increased leptin receptor levels.

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Cited by (22)

Cross talk about the role of Neuropeptide Y in CNS disorders and diseases
2023, Neuropeptides
A peptide composed of a 36 amino acid called Neuropeptide Y (NPY) is employed in a variety of physiological processes to manage and treat conditions affecting the endocrine, circulatory, respiratory, digestive, and neurological systems. NPY naturally binds to G-protein coupled receptors, activating the Y-receptors (Y1-Y5 and y6). The findings on numerous therapeutic applications of NPY for CNS disease are presented in this review by the authors. New targets for treating diseases will be revealed by medication combinations that target NPY and its receptors. This review is mainly focused on disorders such as anxiety, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Machado Joseph disease, multiple sclerosis, schizophrenia, depression, migraine, alcohol use disorder, and substance use disorder. The findings from the preclinical studies and clinical studies covered in this article may help create efficient therapeutic plans to treat neurological conditions on the one hand and psychiatric disorders on the other. They may also open the door to the creation of novel NPY receptor ligands as medications to treat these conditions.
Nicotine’ actions on energy balance: Friend or foe?
2021, Pharmacology and Therapeutics
Citation Excerpt :
α7nAChR also co-localize with α-melanocyte-stimulating hormone (α -MSH, a product of POMC processing) and NPY in hypothalamic cells (Souza et al., 2019). In fact, several studies have showed that nicotine modulates energy intake by altering the expression of orexigenic and anorexigenic peptides in the ARC (Bishop, Parker, & Coscina, 2002; Fornari et al., 2007; Frankish et al., 1995; Hur, Hong, Choi, Shin, & Chun, 2010; Jang et al., 2003; Martinez de Morentin et al., 2012; Mineur et al., 2011). Activation of POMC neurons increases the release of melanocortin peptides, including, α-MSH, and β-endorphin.
Obesity has reached pandemic proportions and is associated with severe comorbidities, such as type 2 diabetes mellitus, hepatic and cardiovascular diseases, and certain cancer types. However, the therapeutic options to treat obesity are limited. Extensive epidemiological studies have shown a strong relationship between smoking and body weight, with non-smokers weighing more than smokers at any age. Increased body weight after smoking cessation is a major factor that interferes with their attempts to quit smoking. Numerous controlled studies in both humans and rodents have reported that nicotine, the main bioactive component of tobacco, exerts a marked anorectic action. Furthermore, nicotine is also known to modulate energy expenditure, by regulating the thermogenic activity of brown adipose tissue (BAT) and the browning of white adipose tissue (WAT), as well as glucose homeostasis. Many of these actions occur at central level, by controlling the activity of hypothalamic neuropeptide systems such as proopiomelanocortin (POMC), or energy sensors such as AMP-activated protein kinase (AMPK). However, direct impact of nicotine on metabolic tissues, such as BAT, WAT, liver and pancreas has also been described. Here, we review the actions of nicotine on energy balance. The relevance of this interaction is interesting, because considering the restricted efficiency of obesity treatments, a possible complementary approach may focus on compounds with known pharmacokinetic profile and pharmacological actions, such as nicotine or nicotinic acetylcholine receptors signaling.
The Role of Neuropeptide Y (NPY) in Alcohol and Drug Abuse Disorders
2017, International Review of Neurobiology
Citation Excerpt :
As observed in numerous systems within the brain, chronic drug exposure induces alterations primarily opposite to those found following acute treatment. Chronic cigarette smoke or nicotine treatment has been found to decrease hypothalamic NPY and upregulate Y1 receptor density (Chen et al., 2007; Frankish et al., 1995; Jang et al., 2003; Kane, Parker, & Li, 2001). Interestingly, an increase in NPY following chronic nicotine exposure has been observed in some studies (Li et al., 2000).
Neuropeptide Y (NPY) is a neuromodulator that is widely expressed throughout the central nervous system (CNS) and which is cosecreted with classic neurotransmitters including GABA and glutamate. There is a long history of research implicating a role for NPY in modulating neurobiological responses to alcohol (ethanol) as well as other drugs of abuse. Both ethanol exposure and withdrawal from chronic ethanol have been shown to produce changes in NPY and NPY receptor protein levels and mRNA expression in the CNS. Importantly, manipulations of NPY Y1 and Y2 receptor signaling have been shown to alter ethanol consumption and self-administration in a brain region-specific manner, with Y1 receptor activation and Y2 receptor blockade in regions of the extended amygdala promoting robust reductions of ethanol intake. Similar observations have been made in studies examining neurobiological responses to nicotine, psychostimulants, and opioids. When taken together with observations of potential genetic linkage between the NPY system and the human alcohol abuse disorders, NPY represents a promising target for treating problematic alcohol and drug use, and in protecting individuals from relapse during abstinence.
Involvement of hypothalamic neuropeptide Y in pentazocine induced suppression of food intake in rats
2014, Neuropeptides
The potent orexigenic peptide neuropeptide Y (NPY) has been considered as a possible endogenous ligand for a subpopulation of sigma receptors (SigR). However, their mutual interaction with reference to feeding behavior remains poorly understood. In the present study, we explored the possible interaction between sigma1 receptors (Sig1R) agonist, pentazocine, and NPY on food intake in satiated rats. While pentazocine dose-dependently reduced the food intake, NPY significantly increased it at 2, 4 and 6 h post injection time points. In combination studies, pretreatment with NPY (0.1 nmol/rat, intra-PVN) normalized the inhibitory effect of pentazocine (60 μg/rat, intra-PVN) on food intake. Similarly, pre-treatment with pentazocine (30 μg/rat, intra-PVN) significantly antagonized the orexigenic effect of NPY (0.5 and 1.0 nmol/rat, intra-PVN). Moreover, pentazocine treatment decreased NPY immunoreactivity in arcuate (ARC), paraventricular (PVN), dorsomedial (DMH) and ventromedial (VMH) nuclei of hypothalamus. However, no change was observed in lateral hypothalamus (LH). Study implicates the reduced NPY immunoreactivity for the anorectic effect observed following pentazocine injections. Therefore, the concomitant activation of the NPYergic system along with the Sig1R agonist treatment may serve a useful purpose in the management of the unwanted side effects related to energy homeostasis.
Plasma neuropeptide Y levels relate cigarette smoking and smoking cessation to body weight regulation
2012, Regulatory Peptides
Citation Excerpt :
Weight reducing effect of nicotine is principally achieved by suppressing the appetite and augmenting energy expenditure [28–31]. Mechanistically, nicotine and cigarette smoking have been shown to modulate body weight by interfering with NPY and leptin signaling [28,32,33]. However the studies have been inconsistent and are largely based on animal models.
Loss and disproportionate gain of body weight often seen respectively in smokers and quitters are believed to be due to disrupted energy homeostasis induced by nicotine, the major constituent of cigarette smoke. Energy homeostasis is suggested to be regulated by the coordinated actions of peripheral adipose tissue derived leptin and the brain hypothalamic orexigenic neuropeptide Y (NPY). While the studies probing the role of leptin and NPY in weight modulating effect of nicotine have so far been inconsistent and based largely on animal systems, there is a paucity of data involving human subjects. Here we measured the plasma levels of orexigenic neuropeptide Y (NPY) and leptin in 35 non-smokers and 31 cigarette smokers before and three months after smoking cessation. Compared to non-smokers, smokers were leaner and had reduced NPY and leptin levels. Smoking cessation resulted in a significant weight gain and increased waist circumference accompanied by increased leptin and NPY levels. NPY levels were significantly correlated with body weight (r = 0.43, p < 0.05), BMI (r = 0.41, p < 0.05), and waist circumference (r = 0.37, p < 0.05), while leptin correlated with BMI (r = 0.42, p < 0.05) and waist circumference (r = 0.39, p < 0.05). Association of leptin with smoking status, but not that of NPY, was lost after controlling for anthropometric parameters. Weight modulating effect of cigarette smoke may thus involve its direct action on NPY, independent of leptin. Altered leptin levels in smokers and quitters may merely reflect changes in body weight or precisely fat mass.
Effect of nicotine on feeding and body weight in rats: Involvement of cocaine- and amphetamine-regulated transcript peptide
2011, Behavioural Brain Research
Citation Excerpt :
In PVN and ARC, NPY and leptin receptors are co-localized with CART [3,40,52]. Nicotine influenced both these systems at the level of PVN and ARC [25,38]. CART in the PVN and ARC plays an important role in the energy metabolism [58,61,63,64].
While nicotine treatment to rodents causes a transient anorexia and persistent weight loss, withdrawal produces hyperphagia and weight gain. Herein, we test the hypothesis that endogenous anorectic peptide cocaine- and amphetamine-regulated transcript (CART) may be involved in these nicotine triggered physiological disturbances. In acute study, an anorectic effect of intraperitoneal nicotine was significantly potentiated by intracerebroventricular pre-treatment with CART at 2 and 4 h post-injection time-points. In chronic study, following an initial reduction, food intake, but not body weight, was progressively restored to normal. On the other hand, termination of chronic nicotine treatment resulted in significant hyperphagia and weight gain. These effects of nicotine were abolished if the rats were concomitantly treated with CART. An immunohistochemical profile of hypothalamic CART was studied following different nicotine treatment conditions. Acute nicotine treatment caused a significant increase above control in the CART-immunoreactive cells and fibers in the hypothalamic paraventricular (PVN) and fibers in the arcuate (ARC) nuclei. However, chronic nicotine administration had no effect on the CART-immunoreactivity in the PVN and ARC. While nicotine withdrawal reduced the population of CART-immunoreactive cells and fibers in the PVN, the immunoreactivity in the ARC fibers was increased. The results suggest that hypothalamic CART may process the acute, chronic and withdrawal effects of nicotine on feeding and body weight.

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Short communicationNicotine administration decreases neuropeptide Y expression and increases leptin receptor expression in the hypothalamus of food-deprived rats

Abstract

Mol. Brain Res.

Ann. Epidemiol.

Cell

Brain Res.

Brain Res.

Neurosci. Lett.

Cell

Physiol. Behav.

Life Sci.

Altered expression of hypothalamic neuropeptide mRNAs in food-restricted and food-deprived rats

Neuroendocrinology