Hypothalamic inflammation and the central nervous system control of energy homeostasis

Pimentel, Gustavo D.; Ganeshan, Kirthana; Carvalheira, José Barreto Campello

doi:10.1016/j.mce.2014.06.005

Cited by 32 publications

(25 citation statements)

References 144 publications

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“…; Pimentel et al . ; Timper and Bruning ; Jin and Diano ). In male mice, exposure to HF diet impairs insulin‐dependent depolarization of POMC neurons (Qiu et al .…”

Section: Discussionmentioning

confidence: 99%

“…Together, these observations identify injury to Sim1 neurons in the PVN, rather than to POMC neurons in the arcuate nucleus, as a common feature underlying defects in energy homeostasis induced by exposure to a hypercaloric HF diet in male and female mice. Exposure to HF diet induces whole body insulin resistance and, in the hypothalamus, impaired neuronal function, synaptogenesis, and damaged mitochondria (Schneeberger et al 2013;Kleinridders et al 2014;Pimentel et al 2014;Timper and Bruning 2017;Jin and Diano 2018). In male mice, exposure to HF diet impairs insulin-dependent depolarization of POMC neurons (Qiu et al 2018).…”

Section: Discussionmentioning

confidence: 99%

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Injury to hypothalamic Sim1 neurons is a common feature of obesity by exposure to high‐fat diet in male and female mice

Nyamugenda

Trentzsch

Russell

et al. 2019

Journal of Neurochemistry

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The hypothalamus is essential for regulation of energy homeostasis and metabolism. Feeding hypercaloric, high‐fat (HF) diet induces hypothalamic arcuate nucleus injury and alters metabolism more severely in male than in female mice. The site(s) and extent of hypothalamic injury in male and female mice are not completely understood. In the paraventricular nucleus (PVN) of the hypothalamus, single‐minded family basic helix‐loop helix transcription factor 1 (Sim1) neurons are essential to control energy homeostasis. We tested the hypothesis that exposure to HF diet induces injury to Sim1 neurons in the PVN of male and female mice. Mice expressing membrane‐bound enhanced green fluorescent protein (mEGFP) in Sim1 neurons (Sim1‐Cre:Rosa‐mEGFP mice) were generated to visualize the effects of exposure to HF diet on these neurons. Male and female Sim1‐Cre:Rosa‐mEGFP mice exposed to HF diet had increased weight, hyperleptinemia, and developed hepatosteatosis. In male and female mice exposed to HF diet, expression of mEGFP was reduced by > 40% in Sim1 neurons of the PVN, an effect paralleled by cell apoptosis and neuronal loss, but not by microgliosis. In the arcuate nucleus of the Sim1‐Cre:Rosa‐mEGFP male mice, there was decreased alpha‐melanocyte‐stimulating hormone in proopiomelanocortin neurons projecting to the PVN, with increased cell apoptosis, neuronal loss, and microgliosis. These defects were undetectable in the arcuate nucleus of female mice exposed to the HF diet. Thus, injury to Sim1 neurons of the PVN is a shared feature of exposure to HF diet in mice of both sexes, while injury to proopiomelanocortin neurons in arcuate nucleus is specific to male mice. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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“…; Pimentel et al . ; Timper and Bruning ; Jin and Diano ). In male mice, exposure to HF diet impairs insulin‐dependent depolarization of POMC neurons (Qiu et al .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Injury to hypothalamic Sim1 neurons is a common feature of obesity by exposure to high‐fat diet in male and female mice

Nyamugenda

Trentzsch

Russell

et al. 2019

Journal of Neurochemistry

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“…This involves activation of microglia, the tissue-resident macrophages in the CNS. Local inflammation in the mediobasal hypothalamus (encompassing the ARC, the anterior part of the PVN and the ME) promotes endoplasmic reticulum (ER) stress in hypothalamic neurons, leading to insulin and leptin resistance (Pimentel et al, 2014; Kleinridders et al, 2009). It has recently been demonstrated that constitutive activation of the proinflammatory c-Jun N-terminal kinase 1 (JNK1) pathway in AgRP neurons increases spontaneous firing in these cells, along with neuronal and systemic leptin resistance, resulting in hyperphagia (overeating), increased weight gain and adiposity (Tsaousidou et al, 2014).…”

Section: Hypothalamic Pathways Involved In Dysregulated Energy Homeosmentioning

confidence: 99%

Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity

Timper

Brüning

2017

Disease Models &Amp; Mechanisms

582

545

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The ‘obesity epidemic’ represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure. The arcuate neurons are tightly connected to other specialized neuronal subpopulations within the hypothalamus, but also to various extrahypothalamic brain regions, allowing a coordinated behavioral response. This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity. The potential impact of recent research findings in the field on therapeutic treatment strategies for human obesity is also discussed.

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“…If any of the above mechanisms are involved, the hypothalamus will also be involved. The hypothalamus regulates many homeostatic systems, including energy/metabolic homeostasis and, in turn, hundreds of neuronal, endocrine and humoral signals converge on it . Of potential importance, the hypothalamic melanocortin system has been implicated in cancer cachexia.…”

Section: Discussionmentioning

confidence: 99%

Modulation of synaptic inputs in magnocellular neurones in a rat model of cancer cachexia

Yokoyama

Terawaki²,

Minami

et al. 2018

J Neuroendocrinology

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In cancer cachexia, abnormal metabolism and neuroendocrine dysfunction cause anorexia, tissue damage and atrophy, which can in turn alter body fluid balance. Arginine vasopressin, which regulates fluid homeostasis, is secreted by magnocellular neurosecretory cells (MNCs) of the hypothalamic supraoptic nucleus. Arginine vasopressin secretion by MNCs is regulated by both excitatory and inhibitory synaptic activity, alterations in plasma osmolarity and various peptides, including angiotensin II. In the present study, we used whole-cell patch-clamp recordings of brain slices to determine whether hyperosmotic stimulation and/or angiotensin II potentiate excitatory synaptic input in a rat model of cancer cachexia, similar to their effects in normal (control) rats. Hyperosmotic (15 and 60 mmol L mannitol) stimulation and angiotensin II (0.1 μmol L ) increased the frequency, but not the amplitude, of miniature excitatory postsynaptic currents in normal rats; in model rats, both effects were significantly attenuated. These results suggest that cancer cachexia alters supraoptic MNC sensitivity to osmotic and angiotensin II stimulation.

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Hypothalamic inflammation and the central nervous system control of energy homeostasis

Cited by 32 publications

References 144 publications

Injury to hypothalamic Sim1 neurons is a common feature of obesity by exposure to high‐fat diet in male and female mice

Injury to hypothalamic Sim1 neurons is a common feature of obesity by exposure to high‐fat diet in male and female mice

Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity

Modulation of synaptic inputs in magnocellular neurones in a rat model of cancer cachexia

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