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AgRP/NPY neurons

P S Dalvi, J A Chalmers, V Luo, D-Yd Han, L Wellhauser, Y Liu, D Q Tran, J Castel, S Luquet, M B Wheeler, D D Belsham
BACKGROUND: Consumption of dietary fat is one of the key factors leading to obesity. High-fat diet (HFD)-induced obesity is characterized by induction of inflammation in the hypothalamus; however, the temporal regulation of proinflammatory markers and their impact on hypothalamic appetite-regulating neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons remains undefined. METHODS: Mice were injected with an acute lipid infusion for 24 h or fed a HFD over 8-20 weeks...
October 24, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Naiyan Chen, Hiroki Sugihara, Jinah Kim, Zhanyan Fu, Boaz Barak, Mriganka Sur, Guoping Feng, Weiping Han
Multiple hypothalamic neuronal populations that regulate energy balance have been identified. Although hypothalamic glia exist in abundance and form intimate structural connections with neurons, their roles in energy homeostasis are less known. Here we show that selective Ca(2+) activation of glia in the mouse arcuate nucleus (ARC) reversibly induces increased food intake while disruption of Ca(2+) signaling pathway in ARC glia reduces food intake. The specific activation of ARC glia enhances the activity of agouti-related protein/neuropeptide Y (AgRP/NPY)-expressing neurons but induces no net response in pro-opiomelanocortin (POMC)-expressing neurons...
October 18, 2016: ELife
Jia Sun, Yong Gao, Ting Yao, Yiru Huang, Zhenyan He, Xingxing Kong, Kai-Jiang Yu, Rui-Tao Wang, Hongbo Guo, Jianqun Yan, Yongsheng Chang, Hong Chen, Philipp E Scherer, Tiemin Liu, Kevin W Williams
OBJECTIVE: Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation - including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined...
October 2016: Molecular Metabolism
Miranda D Johnson, Sebastien G Bouret, Ambrose A Dunn-Meynell, Christina Neuner Boyle, Thomas A Lutz, Barry E Levin
Selectively bred diet-induced obese (DIO) rats become obese on a high fat diet and are leptin resistant before becoming obese. As compared to diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (αMSH; from pro-opiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC, but not NPY/AgRP neurons...
September 14, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Bora Lee, Seunghee Lee, Soo-Kyung Lee, Jae W Lee
Neurons in the hypothalamic arcuate nucleus relay and translate important cues from the periphery into the central nervous system. However, the gene regulatory program directing their development remains poorly understood. Here we report that the LIM-homeodomain transcription factor Isl1 is expressed in several subpopulations of developing arcuate neurons and plays crucial roles in their fate specification. Mice with conditional deletion of the Isl1 gene in developing hypothalamus display severe deficits in both feeding and linear growth...
August 30, 2016: Development
Ji Xu, Alexander M Bernstein, Angela Wong, Xiao-Hong Lu, Sheraz Khoja, X William Yang, Daryl L Davies, Paul Micevych, Michael V Sofroniew, Baljit S Khakh
UNLABELLED: P2X4 receptors are ATP-gated cation channels that are widely expressed in the nervous system. To identify P2X4 receptor-expressing cells, we generated BAC transgenic mice expressing tdTomato under the control of the P2X4 receptor gene (P2rx4). We found sparse populations of tdTomato-positive neurons in most brain areas with patterns that matched P2X4 mRNA distribution. tdTomato expression within microglia was low but was increased by an experimental manipulation that triggered microglial activation...
August 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lihong Hao, Zhenyu Sheng, Joseph Potian, Adam Deak, Christine Rohowsky-Kochan, Vanessa H Routh
A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast...
October 1, 2016: Brain Research
João A B Pedroso, Marina A Silveira, Leandro B Lima, Isadora C Furigo, Thais T Zampieri, Angela M Ramos-Lobo, Daniella C Buonfiglio, Pryscila D S Teixeira, Renata Frazão, Jose Donato
Weight regain frequently follows interventions that reduce body weight, leading to a failure in long-term obesity treatment. Inhibitory proteins of the leptin signaling pathway, such as the suppressor of cytokine signaling 3 (SOCS3), have been studied in conditions that predispose animals to obesity. However, whether SOCS3 modulates postrestriction hyperphagia and weight regain remains unknown. Mice lacking SOCS3 protein specifically in leptin receptor (LepR)-expressing cells (LepR SOCS3 knockout [KO]) were generated and studied in fasting and refeeding conditions...
October 2016: Endocrinology
Alain Juan De Solis, Arian F Baquero, Camdin M Bennett, Kevin L Grove, Lori M Zeltser
OBJECTIVE: Humans and animals exposed to undernutrition (UN) during development often experience accelerated "catch-up" growth when food supplies are plentiful. Little is known about the mechanisms regulating early growth rates. We previously reported that actions of leptin and presynaptic inputs to orexigenic NPY/AgRP/GABA (NAG) neurons in the arcuate nucleus of the hypothalamus are almost exclusively excitatory during the lactation period, since neuronal and humoral inhibitory systems do not develop until after weaning...
March 2016: Molecular Metabolism
Leigh Wellhauser, Jennifer A Chalmers, Denise D Belsham
The arcuate nucleus of the hypothalamus represents a key center for the control of appetite and feeding through the regulation of 2 key neuronal populations, notably agouti-related peptide/neuropeptide Y and proopimelanocortin (POMC)/cocaine- and amphetamine-regulated transcript neurons. Altered regulation of these neuronal networks, in particular the dysfunction of POMC neurons upon high-fat consumption, is a major pathogenic mechanism involved in the development of obesity and type 2 diabetes mellitus. Efforts are underway to preserve the integrity or enhance the functionality of POMC neurons in order to prevent or treat these metabolic diseases...
April 2016: Molecular Endocrinology
Yasuhiko Minokoshi
Feeding behavior is regulated by homeostatic and hedonic mechanisms. NPY/AgRP neurons in the arcuate hypothalamus are involved in the homeostatic regulation, and dopaminergic neurons in the ventral tegmental area regulating the nucleus of accumbens are involved in the hedonic regulation, respectively. Food preference also appears to be regulated by both homeostatic and hedonic mechanisms. However, molecular mechanism for food preference regulation remains elusive and further studies are necessary.
March 2016: Clinical Calcium
Agustina Cabral, Enrique Portiansky, Edith Sánchez-Jaramillo, Jeffrey M Zigman, Mario Perello
Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN...
May 2016: Psychoneuroendocrinology
Gerard Aragonès, Andrea Ardid-Ruiz, Maria Ibars, Manuel Suárez, Cinta Bladé
Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity. This review summarizes the existing literature on potentially valuable nutrients and food components to reverse leptin resistance...
August 2016: Molecular Nutrition & Food Research
Nicole H Rogers, Heidi Walsh, Oscar Alvarez-Garcia, Seongjoon Park, Bruce Gaylinn, Michael O Thorner, Roy G Smith
Aging is associated with attenuated ghrelin signaling. During aging, chronic caloric restriction (CR) produces health benefits accompanied by enhanced ghrelin production. Ghrelin receptor (GH secretagogue receptor 1a) agonists administered to aging rodents and humans restore the young adult phenotype; therefore, we tested the hypothesis that the metabolic benefits of CR are mediated by endogenous ghrelin. Three month-old male mice lacking ghrelin (Ghrelin-/-) or ghrelin receptor (Ghsr-/-), and their wild-type (WT) littermates were randomly assigned to 2 groups: ad libitum (AL) fed and CR, where 40% food restriction was introduced gradually to allow Ghrelin-/- and Ghsr-/- mice to metabolically adapt and avoid severe hypoglycemia...
April 2016: Endocrinology
Wei Wei, Kevin Pham, Jesse W Gammons, Daniel Sutherland, Yanyun Liu, Alana Smith, Catherine C Kaczorowski, Kristen M S O'Connell
Obesity is a chronic condition resulting from a long-term pattern of poor diet and lifestyle. Long-term consumption of high-fat diet (HFD) leads to persistent activation and leptin resistance in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH). Here, for the first time, we demonstrate acute effects of HFD on AgRP neuronal excitability and highlight a critical role for diet composition. In parallel with our earlier finding in obese, long-term HFD mice, we found that even brief HFD feeding results in persistent activation of ARH AgRP neurons...
November 23, 2015: Scientific Reports
Matthew S Dicken, Alexander R Hughes, Shane T Hentges
The strength of γ-aminobutyric acid (GABA)-mediated inhibitory synaptic input is a principle determinant of neuronal activity. However, because of differences in the number of GABA afferent inputs and the sites of synapses, it is difficult to directly assay for altered GABA transmission between specific cells. The present study tested the hypothesis that the level of mRNA for the GABA synthetic enzyme glutamate decarboxylase (GAD) can provide a reliable proxy for GABA release. This was tested in a mouse hypothalamic circuit important in the regulation of energy balance...
November 2015: European Journal of Neuroscience
Chunling Yan, Yanlin He, Yuanzhong Xu, Gang Shu, Chunmei Wang, Yongjie Yang, Kenji Saito, Pingwen Xu, Antentor Othrell Hinton, Xiaofeng Yan, Likai Yu, Qi Wu, Patrick Tso, Qingchun Tong, Yong Xu
BACKGROUND/AIMS: Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However, the mechanisms underlying its anorexigenic effects remain to be identified. METHODS: We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) and in neurons that express pro-opiomelanocortin (POMC). We then compared anorexigenic effects of apoA-IV in wild-type mice and in mutant mice lacking melanocortin 4 receptors (MC4Rs; the receptors of AgRP and the POMC gene product)...
2016: Neuroendocrinology
Romana Stark, Alex Reichenbach, Zane B Andrews
The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance)...
December 15, 2015: Molecular and Cellular Endocrinology
Prashanth Anamthathmakula, Maitrayee Sahu, Abhiram Sahu
Hypothalamic neurons expressing neuropeptide Y (NPY) and agouti related-protein (AgRP) are critical regulators of feeding behavior and body weight, and transduce the action of many peripheral signals including leptin and insulin. However, intracellular signaling molecules involved in regulating NPY/AgRP neuronal activity are incompletely understood. Since phosphodiesterase-3B (PDE3B) mediates the hypothalamic action of leptin and insulin on feeding, and is expressed in NPY/AgRP neurons, PDE3B could play a significant role in regulating NPY/AgRP neuronal activity...
September 14, 2015: Neuroscience Letters
Eun Ran Kim, Zhaofei Wu, Hao Sun, Yuanzhong Xu, Leandra R Mangieri, Yong Xu, Qingchun Tong
The hypothalamus is critical for feeding and body weight regulation. Prevailing studies focus on hypothalamic neurons that are defined by selectively expressing transcription factors or neuropeptides including those expressing proopiomelanocortin (POMC) and agouti-related peptides (AgRP). The Cre expression driven by the pancreas-duodenum homeobox 1 promoter is abundant in several hypothalamic nuclei but not in AgRP or POMC neurons. Using this line, we generated mice with disruption of GABA release from a major subset of non-POMC, non-AgRP GABAergic neurons in the hypothalamus...
July 22, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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