Hypothalamic Pomc expression restricted to GABAergic neurons suppresses Npy overexpression and restores food intake in obese mice

Trotta, Milagros; Bello, Estefanía P.; Alsina, Ramiro; Tavella, María Belén; Ferrán, José Luis; Rubinstein, Marcelo; Bumaschny, Viviana Florencia

doi:10.1016/j.molmet.2020.100985

Cited by 25 publications

(20 citation statements)

References 52 publications

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“…In the present study, we provide physiological evidence that in addition to the ARC POMC →PVH and ARC POMC →DMH NPY circuits within the hypothalamus (Balthasar et al, 2005;Shah et al, 2014;Trotta et al, 2020), the ARC POMC →MeA pathway is another important neural circuit that mediates MC4R-mediated anorexic effects. We found that ARC POMC neurons sent axonal projections to the MeA.…”

Section: Discussionmentioning

confidence: 68%

“…Accumulating evidence has demonstrated heterogeneity of ARC POMC neurons (Parton et al, 2007 ; Hentges et al, 2009 ; Williams et al, 2010 ; Sohn et al, 2011 ; Jarvie and Hentges, 2012 ; Shi et al, 2013 ; Qiu et al, 2014 ; Dodd et al, 2018 ; Jones et al, 2019 ; Trotta et al, 2020 ). ARC POMC neurons are neurochemically, anatomically, and functionally heterogeneous (Parton et al, 2007 ; Hentges et al, 2009 ; Williams et al, 2010 ; Sohn et al, 2011 ; Jarvie and Hentges, 2012 ; Shi et al, 2013 ; Qiu et al, 2014 ; Dodd et al, 2018 ; Wei et al, 2018 ; Jones et al, 2019 ; Trotta et al, 2020 ). It has been recently shown that re-expression of the Pomc gene in ARC glutamatergic neurons in ARC specific Pomc KO mice completely normalizes body weight and body composition (Jones et al, 2019 ), although it is unknown if these effects are attributed to decreased food intake or increased energy expenditure, or both.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, POMC rescues exclusively in ARC GABAergic neurons are also able to normalize food intake and significantly reduce body weight. This anorectic effect is mediated by the ARC POMC →DMH NPY projection (Trotta et al, 2020 ). The DMH is innervated largely by GABAergic POMC neurons and NPY expression in the DMH is inversely regulated by POMC expression in ARC GABAergic neurons (Trotta et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…This anorectic effect is mediated by the ARC POMC →DMH NPY projection (Trotta et al, 2020 ). The DMH is innervated largely by GABAergic POMC neurons and NPY expression in the DMH is inversely regulated by POMC expression in ARC GABAergic neurons (Trotta et al, 2020 ). These prior studies suggest that fast-acting neurotransmitters (i.e., glutamate and GABA) released from ARC POMC neurons are essential in regulating feeding and body weight.…”

Section: Discussionmentioning

confidence: 99%

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Activation of the ARCPOMC→MeA Projection Reduces Food Intake

Kwon

2020

Front. Neural Circuits

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Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) plays an essential role in the control of food intake and energy expenditure. Melanocortin-4 receptors (MC4Rs) are expressed in key areas that are implicated in regulating energy homeostasis. Although the importance of MC4Rs in the paraventricular hypothalamus (PVH) has been well documented, the role of MC4Rs in the medial amygdala (MeA) on feeding remains controversial. In this study, we specifically examine the role of a novel ARC POMC →MeA neural circuit in the regulation of short-term food intake. To map a local melanocortinergic neural circuit, we use monosynaptic anterograde as well as retrograde viral tracers and perform double immunohistochemistry to determine the identity of the neurons receiving synaptic input from POMC neurons in the ARC. To investigate the role of the ARC POMC →MeA projection on feeding, we optogenetically stimulate channelrhodopsin-2 (ChR2)-expressing POMC fibers in the MeA. Anterograde viral tracing studies reveal that ARC POMC neurons send axonal projections to estrogen receptor-α (ER-α)-and MC4R-expressing neurons in the MeA. Retrograde viral tracing experiments show that the neurons projecting to the MeA is located mainly in the lateral part of the ARC. Optogenetic stimulation of the ARC POMC →MeA pathway reduces short-term food intake. This anorectic effect is blocked by treatment with the MC4R antagonist SHU9119. In addition to the melanocortinergic local circuits within the hypothalamus, this extrahypothalamic ARC POMC →MeA neural circuit would play a role in regulating short-term food intake.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Activation of the ARCPOMC→MeA Projection Reduces Food Intake

Kwon

2020

Front. Neural Circuits

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“…Firstly, DMH NPY gene silencing improves overeating and obesity induced by a high-fat diet ( 103 ); in turn, DMH NPY overexpression leads to increased food intake and weight gain, aggravating diet-induced eating disorders and obesity ( 113 ). Besides, the expression of DMH-NPY is inhibited by ARC GABAergic-proopiomelanocortin neurons ( 114 ), which may contribute to reasonable control of food intake. Secondly, NPY in the lateral hypothalamus increased rat food intake of free choice high-fat high-sucrose and chow diets and Y5R antagonists prevented all of the above results.…”

Section: Npy Indirectly Regulates the Immune Responsementioning

confidence: 99%

Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect

Chen

Liu

et al. 2020

Front. Immunol.

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Neuropeptide Y (NPY), which is widely distributed in the nervous system, is involved in regulating a variety of biological processes, including food intake, energy metabolism, and emotional expression. However, emerging evidence points to NPY also as a critical transmitter between the nervous system and immune system, as well as a mediator produced and released by immune cells. In vivo and in vitro studies based on gene-editing techniques and specific NPY receptor agonists and antagonists have demonstrated that NPY is responsible for multifarious direct modulations on immune cells by acting on NPY receptors. Moreover, via the central or peripheral nervous system, NPY is closely connected to body temperature regulation, obesity development, glucose metabolism, and emotional expression, which are all immunomodulatory factors for the immune system. In this review, we focus on the direct role of NPY in immune cells and particularly discuss its indirect impact on the immune response.

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