Leptin receptor-positive and leptin receptor-negative proopiomelanocortin neurons innervate an identical set of brain structures

Lima, Leandro B.; Metzger, Martin; Furigo, Isadora C.; Donato, José

doi:10.1016/j.brainres.2016.06.024

Cited by 16 publications

(7 citation statements)

References 56 publications

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“…While it is well-known that leptin activates POMC neurons in the ARC, leptin's action in the ARC is not limited on POMC neurons. Leptin receptor and leptin-induced immediate signals are observed in ARC neurons including non-POMC neurons (Elias et al, 2000; Lima et al, 2016). There could be unidentified and/or uncharacterized satiety neurons in the ARC.…”

Section: Discussionmentioning

confidence: 99%

Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness

et al. 2016

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The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes. T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca2+ concentration ([Ca2+]i) in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10−5–10−2 M dose dependently increased [Ca2+]i in 12–16% of ARC neurons. The sucralose-induced [Ca2+]i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca2+]i increase was inhibited under an extracellular Ca2+-free condition and in the presence of an L-type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC) neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular activation mainly occurs on non-POMC leptin-responding neurons and contributes to glucose responding. Endogenous sweet molecules including glucose may regulate energy homeostasis through sweet taste receptors on glucose-and leptin-responsive neurons in the ARC.

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Section: Discussionmentioning

confidence: 99%

Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness

et al. 2016

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“…LepRb has a cytoplasmic tail responsible for the phosphorylation and activation of signal transducer and activator for transcription 3 (pSTAT3) ( Vaisse et al, 1996 ; Bjorbaek et al, 1997 ). Numerous studies have investigated the distribution of LepRb-expressing cells in the rodent brain by using neuroanatomical techniques such as in situ hybridization and immunohistochemistry for pSTAT3 ( Hakansson et al, 1996 ; Elmquist et al, 1997 ; Mercer et al, 1998 ; Hubschle et al, 2001 ; Munzberg et al, 2003 ; Fulton et al, 2006 ; Caron et al, 2010 ; Laque et al, 2013 ; Maniscalco and Rinaman, 2014 ; Lima et al, 2016 ). Transgenic mouse lines that express reporter proteins under the control of the LepRb gene promoter have also been used to map LepRb-expressing brain cells ( Leshan et al, 2009 , 2010 ; Scott et al, 2009 ; Patterson et al, 2011 ; Lima et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Leptin Receptor Expression in Mouse Intracranial Perivascular Cells

Yuan

Caron

et al. 2018

Front. Neuroanat.

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Past studies have suggested that non-neuronal brain cells express the leptin receptor. However, the identity and distribution of these leptin receptor-expressing non-neuronal brain cells remain debated. This study assessed the distribution of the long form of the leptin receptor (LepRb) in non-neuronal brain cells using a reporter mouse model in which LepRb-expressing cells are permanently marked by tdTomato fluorescent protein (LepRb-CretdTomato). Double immunohistochemistry revealed that, in agreement with the literature, the vast majority of tdTomato-tagged cells across the mouse brain were neurons (i.e., based on immunoreactivity for NeuN). Non-neuronal structures also contained tdTomato-positive cells, including the choroid plexus and the perivascular space of the meninges and, to a lesser extent, the brain. Based on morphological criteria and immunohistochemistry, perivascular cells were deduced to be mainly pericytes. Notably, tdTomato-positive cells were immunoreactive for vitronectin and platelet derived growth factor receptor beta (PDGFBR). In situ hybridization studies confirmed that most tdTomato-tagged perivascular cells were enriched in leptin receptor mRNA (all isoforms). Using qPCR studies, we confirmed that the mouse meninges were enriched in Leprb and, to a greater extent, the short isoforms of the leptin receptor. Interestingly, qPCR studies further demonstrated significantly altered expression for Vtn and Pdgfrb in the meninges and hypothalamus of LepRb-deficient mice. Collectively, our data demonstrate that the only intracranial non-neuronal cells that express LepRb in the adult mouse are cells that form the blood-brain barrier, including, most notably, meningeal perivascular cells. Our data suggest that pericytic leptin signaling plays a role in the integrity of the intracranial perivascular space and, consequently, may provide a link between obesity and numerous brain diseases.

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“…(Figure 3F) injections. To further demonstrate that PVH of mice exhibit few leptin‐responsive cells, we analysed brain sections of LepR‐reporter mice that allow the visualisation of LepR‐expressing cells through the expression of a fluorescent reporter protein 15,16,50 . It is worth noting that LepR‐reporter mice also allow the visualisation of axonal projections 50 .…”

Section: Resultsmentioning

confidence: 99%

Differences between rats and mice in the leptin action on the paraventricular nucleus of the hypothalamus: Implications for the regulation of the hypothalamic‐pituitary‐thyroid axis

Campos

Teixeira

Wasinski

et al. 2020

J Neuroendocrinology

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Leptin is a hormone produced by the adipose tissue and its circulating levels reflect the amount of fat stored in the body. 1,2 The brain is the main site where leptin acts to influence numerous metabolic functions, including food intake, energy expenditure and nutrient oxidation. 3 Loss-of-function mutations in the genes encoding leptin or the leptin receptor (LepR) lead to severe obesity, hyperphagia,

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Leptin receptor-positive and leptin receptor-negative proopiomelanocortin neurons innervate an identical set of brain structures

Cited by 16 publications

References 56 publications

Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness

Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness

Leptin Receptor Expression in Mouse Intracranial Perivascular Cells

Differences between rats and mice in the leptin action on the paraventricular nucleus of the hypothalamus: Implications for the regulation of the hypothalamic‐pituitary‐thyroid axis

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