scholarly journals Nicotine excites hypothalamic arcuate anorexigenic proopiomelanocortin neurons and orexigenic neuropeptide Y neurons: similarities and differences

2011 ◽  
Vol 106 (3) ◽  
pp. 1191-1202 ◽  
Author(s):  
Hao Huang ◽  
Youfen Xu ◽  
Anthony N. van den Pol

Two of the biggest health problems facing us today are addiction to nicotine and the increased prevalence of obesity. Interestingly, nicotine attenuates obesity, but the underlying mechanism is not clear. Here we address the hypothesis that if weight-reducing actions of nicotine are mediated by anorexigenic proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus, nicotine should excite these cells. Nicotine at concentrations similar to those found in smokers, 100–1,000 nM, excited POMC cells by mechanisms based on increased spike frequency, depolarization of membrane potential, and opening of ion channels. This was mediated by activation of both α7 and α4β2 nicotinic receptors; by itself, this nicotine-mediated excitation could explain weight loss caused by nicotine. However, in control experiments nicotine also excited the orexigenic arcuate nucleus neuropeptide Y (NPY) cells. Nicotine exerted similar actions on POMC and NPY cells, with a slightly greater depolarizing action on POMC cells. Immunocytochemistry revealed cholinergic axons terminating on both cell types. Nicotine actions were direct in both cell types, with nicotine depolarizing the membrane potentials and reducing input resistance. We found no differences in the relative desensitization to nicotine between POMC and NPY neurons. Nicotine inhibited excitatory synaptic activity recorded in NPY, but not POMC, cells. Nicotine also excited hypocretin/orexin neurons that enhance cognitive arousal, but the responses were smaller than in NPY or POMC cells. Together, these results indicate that nicotine has a number of similar actions, but also a few different actions, on POMC and NPY neurons that could contribute to the weight loss associated with smoking.

2009 ◽  
Vol 297 (1) ◽  
pp. R100-R110 ◽  
Author(s):  
Csilla Becskei ◽  
Thomas A. Lutz ◽  
Thomas Riediger

Fasting activates orexigenic neuropeptide Y neurons in the hypothalamic arcuate nucleus (ARC) of mice, which is reversed by 2 h refeeding with standard chow. Here, we investigated the contribution of diet-derived macronutrients and anorectic hormones to the reversal of the fasting-induced ARC activation during 2 h refeeding. Refeeding of 12-h-fasted mice with a cellulose-based, noncaloric mash induced only a small reduction in c-Fos expression. Refeeding with diets, containing carbohydrates, protein, or fat alone reversed it similar to chow; however, this effect depended on the amount of intake. The fasting-induced ARC activation was unchanged by subcutaneously injected amylin, CCK (both 20 μg/kg), insulin (0.2 U/kg and 0.05 U/kg) or leptin (2.6 mg/kg). Insulin and leptin had no effect on c-Fos expression in neuropeptide Y or proopiomelanocortin-containing ARC neurons. Interestingly, CCK but not amylin reduced the ghrelin-induced c-Fos expression in the ARC in ad libitum-fed mice, suggesting that CCK may inhibit orexigenic ARC neurons when acting together with other feeding-related signals. We conclude that all three macronutrients and also non-nutritive, ingestion-dependent signals contribute to an inhibition of orexigenic ARC neurons after refeeding. Similar to the previously demonstrated inhibitory in vivo action of peptide YY, CCK may be a postprandial mediator of ARC inhibition.


Aging ◽  
2011 ◽  
Vol 3 (11) ◽  
pp. 1092-1097 ◽  
Author(s):  
Yuko Maejima ◽  
Daisuke Kohno ◽  
Yusaku Iwasaki ◽  
Toshihiko Yada

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pernille Barkholt ◽  
Kristoffer T. G. Rigbolt ◽  
Mechthilde Falkenhahn ◽  
Thomas Hübschle ◽  
Uwe Schwahn ◽  
...  

Abstract The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.


Neuropeptides ◽  
2012 ◽  
Vol 46 (6) ◽  
pp. 285-289 ◽  
Author(s):  
Haruaki Kageyama ◽  
Fumiko Takenoya ◽  
Satoshi Hirako ◽  
Nobuhiro Wada ◽  
Yuri Kintaka ◽  
...  

2011 ◽  
Vol 499 (3) ◽  
pp. 194-198 ◽  
Author(s):  
Daisuke Kohno ◽  
Hideyuki Sone ◽  
Shigeyasu Tanaka ◽  
Hideharu Kurita ◽  
Darambazar Gantulga ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Shao-Xian Wang ◽  
Jia-Xu Chen ◽  
Guang-Xin Yue ◽  
Ming-Hua Bai ◽  
Mei-Jing Kou ◽  
...  

The arcuate nucleus (ARC) in the basal of hypothalamus plays an important role in appetite regulation and energy balance. We sought to investigate the central neuroendocrine mechanism of appetite decrease and weight loss under chronic stress by observing the regulatory effects of Xiaoyaosan decoction in the expression of leptin receptor (ob-R) and neuropeptide Y (NPY) in the ARC. Our results showed that bodyweight and food intake of rats in the 21-day stress group increased slower than those of the normal group. Higher contents of Leptin andob-Rwere noted in the 21-day stress group compared with control rats, while NPY expression was not statistically different. Xiaoyaosan powder can significantly downregulate the contents of leptin andob-Rin the hypothalamus of stressed rats. These findings suggest that increase ofob-Rexpression in the ARC is possibly one key central neuroendocrine change for the somatic discomfort. Weight loss and decreased food intake in rats caused by the binding of leptin toob-Rin hypothalamus do not appear to utilize the NPY pathway. This study also suggests thatob-Rin the ARC may act as the target of Xiaoyaosan in regulating the symptoms such as appetite decrease and bodyweight loss under chronic stress.


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