Special Issue "Neuroendocrine Control of Energy Metabolism"

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: 31 October 2021.

Special Issue Editors

Prof. Giancarlo Panzica
E-Mail Website
Guest Editor
Univ Turin, Dept Neurosci, Rita Levi Montalcini, I-10126 Turin, Italy
Interests: Hypothalamus, Metabolism disrupting chemicals, Reproduction and metabolism, Brain sex differences, Endocrine disruptors
Dr. Stefano Gotti
E-Mail Website
Guest Editor
Univ Turin, Dept Neurosci, Rita Levi Montalcini, I-10126 Turin, Italy
Interests: Endocrine disruptors; Brain sex differences; Feeding brain circuits; Anorexia Nervosa; Neuropeptides
Prof. Dr. Paloma Collado Guirao
E-Mail Website
Guest Editor
Universidad Nacional de Education a Distancia (UNED), Dept. Psycobiology, 28040 Madrid, Spain
Interests: Energy metabolism programming; Metabolic sex differences; Sex steroids and feeding; Feeding brain circuits; obesity and anorexia

Special Issue Information

Dear Colleagues,

The control of energy metabolism is a central event for cell, organ, and organism survival. There are many control levels in energy metabolism, but in this Special Issue, we will concentrate on the neuroendocrine control that is operated through specialized neural (mainly, but not exclusively, hypothalamic) circuits controlling both food intake and energy expenditure. Due to the explosion of obesity and related diseases, the subject of this Special Issue is of particular interest today.

The topics that will be covered by this Special Issue include but are not limited to:

  • Programming of neurohormonal circuits of feeding
  • Gut–brain axis and metabolic control
  • Neuropeptide systems in feeding behavior
  • Neural control of food reward
  • Eating disorders
  • Glial cells and neuroendocrine control
  • Adipose tissue and metabolic neural control
  • Gonadal hormones and feeding
  • Metabolic sex differences
  • Endocrine disruptors and neural control of feeding and energy metabolism

Manuscripts dealing with other pertinent challenging issues are also highly desired.

Prof. Giancarlo Panzica
Prof. Stefano Gotti
Prof. Paloma Collado Guirao
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Hypothalamus
  • Sex differences
  • Feeding behavior
  • Endocrine disruptors
  • Energy metabolism
  • Neuroendocrine control
  • Eating disorders

Published Papers (9 papers)

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Research

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Article
Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice
Metabolites 2021, 11(8), 499; https://doi.org/10.3390/metabo11080499 - 30 Jul 2021
Viewed by 1300
Abstract
A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation [...] Read more.
A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women. Full article
(This article belongs to the Special Issue Neuroendocrine Control of Energy Metabolism)
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Article
Early Postnatal Genistein Administration Affects Mice Metabolism and Reproduction in a Sexually Dimorphic Way
Metabolites 2021, 11(7), 449; https://doi.org/10.3390/metabo11070449 - 10 Jul 2021
Viewed by 1126
Abstract
The phytoestrogen genistein (GEN) may interfere with permanent morphological changes in the brain circuits sensitive to estrogen. Due to the frequent use of soy milk in the neonatal diet, we aimed to study the effects of early GEN exposure on some physiological and [...] Read more.
The phytoestrogen genistein (GEN) may interfere with permanent morphological changes in the brain circuits sensitive to estrogen. Due to the frequent use of soy milk in the neonatal diet, we aimed to study the effects of early GEN exposure on some physiological and reproductive parameters. Mice of both sexes from PND1 to PND8 were treated with GEN (50 mg/kg body weight, comparable to the exposure level in babies fed with soy-based formulas). When adult, we observed, in GEN-treated females, an advanced pubertal onset and an altered estrous cycle, and, in males, a decrease of testicle weight and fecal testosterone concentration. Furthermore, we observed an increase in body weight and altered plasma concentrations of metabolic hormones (leptin, ghrelin, triiodothyronine) limited to adult females. Exposure to GEN significantly altered kisspeptin and POMC immunoreactivity only in females and orexin immunoreactivity in both sexes. In conclusion, early postnatal exposure of mice to GEN determines long-term sex-specific organizational effects. It impairs the reproductive system and has an obesogenic effect only in females, which is probably due to the alterations of neuroendocrine circuits controlling metabolism; thus GEN, should be classified as a metabolism disrupting chemical. Full article
(This article belongs to the Special Issue Neuroendocrine Control of Energy Metabolism)
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Article
Hypothalamic Expression of Neuropeptide Y (NPY) and Pro-OpioMelanoCortin (POMC) in Adult Male Mice Is Affected by Chronic Exposure to Endocrine Disruptors
Metabolites 2021, 11(6), 368; https://doi.org/10.3390/metabo11060368 - 09 Jun 2021
Cited by 1 | Viewed by 974
Abstract
In the arcuate nucleus, neuropeptide Y (NPY) neurons, increase food intake and decrease energy expenditure, and control the activity of pro-opiomelanocortin (POMC) neurons, that decrease food intake and increase energy expenditure. Both systems project to other hypothalamic nuclei such as the paraventricular and [...] Read more.
In the arcuate nucleus, neuropeptide Y (NPY) neurons, increase food intake and decrease energy expenditure, and control the activity of pro-opiomelanocortin (POMC) neurons, that decrease food intake and increase energy expenditure. Both systems project to other hypothalamic nuclei such as the paraventricular and dorsomedial hypothalamic nuclei. Endocrine disrupting chemicals (EDCs) are environmental contaminants that alter the endocrine system causing adverse health effects in an intact organism or its progeny. We investigated the effects of long-term exposure to some EDCs on the hypothalamic NPY and POMC systems of adult male mice that had been previously demonstrated to be a target of some of these EDCs after short-term exposure. Animals were chronically fed for four months with a phytoestrogen-free diet containing two different concentrations of bisphenol A, diethylstilbestrol, tributyltin, or E2. At the end, brains were processed for NPY and POMC immunohistochemistry and quantitatively analyzed. In the arcuate and dorsomedial nuclei, both NPY and POMC immunoreactivity showed a statistically significant decrease. In the paraventricular nucleus, only the NPY system was affected, while the POMC system was not affected. Finally, in the VMH the NPY system was affected whereas no POMC immunoreactive material was observed. These results indicate that adult exposure to different EDCs may alter the hypothalamic circuits that control food intake and energy metabolism. Full article
(This article belongs to the Special Issue Neuroendocrine Control of Energy Metabolism)
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Article
Genistein during Development Alters Differentially the Expression of POMC in Male and Female Rats
Metabolites 2021, 11(5), 293; https://doi.org/10.3390/metabo11050293 - 02 May 2021
Cited by 1 | Viewed by 886
Abstract
Phytoestrogens are considered beneficial for health, but some studies have shown that they may cause adverse effects. This study investigated the effects of genistein administration during the second week of life on energy metabolism and on the circuits regulating food intake. Two different [...] Read more.
Phytoestrogens are considered beneficial for health, but some studies have shown that they may cause adverse effects. This study investigated the effects of genistein administration during the second week of life on energy metabolism and on the circuits regulating food intake. Two different genistein doses, 10 or 50 µg/g, were administered to male and female rats from postnatal day (P) 6 to P13. Physiological parameters, such as body weight and caloric intake, were then analyzed at P90. Moreover, proopiomelanocortin (POMC) expression in the arcuate nucleus (Arc) and orexin expression in the dorsomedial hypothalamus (DMH), perifornical area (PF) and lateral hypothalamus (LH) were studied. Our results showed a delay in the emergence of sex differences in the body weight in the groups with higher genistein doses. Furthermore, a significant decrease in the number of POMC-immunoreactive (POMC-ir) cells in the Arc in the two groups of females treated with genistein was observed. In contrast, no alteration in orexin expression was detected in any of the structures analyzed in either males or females. In conclusion, genistein can modulate estradiol’s programming actions on the hypothalamic feeding circuits differentially in male and female rats during development. Full article
(This article belongs to the Special Issue Neuroendocrine Control of Energy Metabolism)
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Article
Impact of Long-Term HFD Intake on the Peripheral and Central IGF System in Male and Female Mice
Metabolites 2020, 10(11), 462; https://doi.org/10.3390/metabo10110462 - 13 Nov 2020
Cited by 3 | Viewed by 949
Abstract
The insulin-like growth factor (IGF) system is responsible for growth, but also affects metabolism and brain function throughout life. New IGF family members (i.e., pappalysins and stanniocalcins) control the availability/activity of IGFs and are implicated in growth. However, how diet and obesity modify [...] Read more.
The insulin-like growth factor (IGF) system is responsible for growth, but also affects metabolism and brain function throughout life. New IGF family members (i.e., pappalysins and stanniocalcins) control the availability/activity of IGFs and are implicated in growth. However, how diet and obesity modify this system has been poorly studied. We explored how intake of a high-fat diet (HFD) or commercial control diet (CCD) affects the IGF system in the circulation, visceral adipose tissue (VAT) and hypothalamus. Male and female C57/BL6J mice received HFD (60% fat, 5.1 kcal/g), CCD (10% fat, 3.7 kcal/g) or chow (3.1 % fat, 3.4 kcal/g) for 8 weeks. After 7 weeks of HFD intake, males had decreased glucose tolerance (p < 0.01) and at sacrifice increased plasma insulin (p < 0.05) and leptin (p < 0.01). Circulating free IGF1 (p < 0.001), total IGF1 (p < 0.001), IGF2 (p < 0.05) and IGFBP3 (p < 0.01) were higher after HFD in both sexes, with CCD increasing IGFBP2 in males (p < 0.001). In VAT, HFD reduced mRNA levels of IGF2 (p < 0.05), PAPP-A (p < 0.001) and stanniocalcin (STC)-1 (p < 0.001) in males. HFD increased hypothalamic IGF1 (p < 0.01), IGF2 (p < 0.05) and IGFBP5 (p < 0.01) mRNA levels, with these changes more apparent in females. Our results show that diet-induced changes in the IGF system are tissue-, sex- and diet-dependent. Full article
(This article belongs to the Special Issue Neuroendocrine Control of Energy Metabolism)
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Review

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Review
l-Lactate: Food for Thoughts, Memory and Behavior
Metabolites 2021, 11(8), 548; https://doi.org/10.3390/metabo11080548 - 20 Aug 2021
Viewed by 815
Abstract
More and more evidence shows how brain energy metabolism is the linkage between physiological and morphological synaptic plasticity and memory consolidation. Different types of memory are associated with differential inputs, each with specific inputs that are upstream diverse molecular cascades depending on the [...] Read more.
More and more evidence shows how brain energy metabolism is the linkage between physiological and morphological synaptic plasticity and memory consolidation. Different types of memory are associated with differential inputs, each with specific inputs that are upstream diverse molecular cascades depending on the receptor activity. No matter how heterogeneous the response is, energy availability represents the lowest common denominator since all these mechanisms are energy consuming and the brain networks adapt their performance accordingly. Astrocytes exert a primary role in this sense by acting as an energy buffer; glycogen granules, a mechanism to store glucose, are redistributed at glance and conveyed to neurons via the Astrocyte–Neuron Lactate Shuttle (ANLS). Here, we review how different types of memory relate to the mechanisms of energy delivery in the brain. Full article
(This article belongs to the Special Issue Neuroendocrine Control of Energy Metabolism)
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Review
Sensory Circumventricular Organs, Neuroendocrine Control, and Metabolic Regulation
Metabolites 2021, 11(8), 494; https://doi.org/10.3390/metabo11080494 - 29 Jul 2021
Viewed by 770
Abstract
The central nervous system is critical in metabolic regulation, and accumulating evidence points to a distributed network of brain regions involved in energy homeostasis. This is accomplished, in part, by integrating peripheral and central metabolic information and subsequently modulating neuroendocrine outputs through the [...] Read more.
The central nervous system is critical in metabolic regulation, and accumulating evidence points to a distributed network of brain regions involved in energy homeostasis. This is accomplished, in part, by integrating peripheral and central metabolic information and subsequently modulating neuroendocrine outputs through the paraventricular and supraoptic nucleus of the hypothalamus. However, these hypothalamic nuclei are generally protected by a blood-brain-barrier limiting their ability to directly sense circulating metabolic signals—pointing to possible involvement of upstream brain nuclei. In this regard, sensory circumventricular organs (CVOs), brain sites traditionally recognized in thirst/fluid and cardiovascular regulation, are emerging as potential sites through which circulating metabolic substances influence neuroendocrine control. The sensory CVOs, including the subfornical organ, organum vasculosum of the lamina terminalis, and area postrema, are located outside the blood-brain-barrier, possess cellular machinery to sense the metabolic interior milieu, and establish complex neural networks to hypothalamic neuroendocrine nuclei. Here, evidence for a potential role of sensory CVO-hypothalamic neuroendocrine networks in energy homeostasis is presented. Full article
(This article belongs to the Special Issue Neuroendocrine Control of Energy Metabolism)
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Review
Control of Adipose Cell Browning and Its Therapeutic Potential
Metabolites 2020, 10(11), 471; https://doi.org/10.3390/metabo10110471 - 19 Nov 2020
Cited by 5 | Viewed by 969
Abstract
Adipose tissue is the largest endocrine organ in humans and has an important influence on many physiological processes throughout life. An increasing number of studies have described the different phenotypic characteristics of fat cells in adults. Perhaps one of the most important properties [...] Read more.
Adipose tissue is the largest endocrine organ in humans and has an important influence on many physiological processes throughout life. An increasing number of studies have described the different phenotypic characteristics of fat cells in adults. Perhaps one of the most important properties of fat cells is their ability to adapt to different environmental and nutritional conditions. Hypothalamic neural circuits receive peripheral signals from temperature, physical activity or nutrients and stimulate the metabolism of white fat cells. During this process, changes in lipid inclusion occur, and the number of mitochondria increases, giving these cells functional properties similar to those of brown fat cells. Recently, beige fat cells have been studied for their potential role in the regulation of obesity and insulin resistance. In this context, it is important to understand the embryonic origin of beige adipocytes, the response of adipocyte to environmental changes or modifications within the body and their ability to transdifferentiate to elucidate the roles of these cells for their potential use in therapeutic strategies for obesity and metabolic diseases. In this review, we discuss the origins of the different fat cells and the possible therapeutic properties of beige fat cells. Full article
(This article belongs to the Special Issue Neuroendocrine Control of Energy Metabolism)
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Brief Report
Evidence That Agouti-Related Peptide May Directly Regulate Kisspeptin Neurons in Male Sheep
Metabolites 2021, 11(3), 138; https://doi.org/10.3390/metabo11030138 - 26 Feb 2021
Viewed by 533
Abstract
Agouti-related peptide (AgRP) neurons, which relay information from peripheral metabolic signals, may constitute a key central regulator of reproduction. Given that AgRP inhibits luteinizing hormone (LH) secretion and that nutritional suppression of LH elicits an increase in AgRP while suppressing kisspeptin expression in [...] Read more.
Agouti-related peptide (AgRP) neurons, which relay information from peripheral metabolic signals, may constitute a key central regulator of reproduction. Given that AgRP inhibits luteinizing hormone (LH) secretion and that nutritional suppression of LH elicits an increase in AgRP while suppressing kisspeptin expression in the arcuate nucleus (ARC) of the hypothalamus, we sought to examine the degree to which AgRP could directly regulate ARC kisspeptin neurons. Hypothalamic tissue was collected from four castrated male sheep (10 months of age) and processed for the detection of protein (AgRP input to kisspeptin neurons) using immunohistochemistry and mRNA for melanocortin 3 and 4 receptors (MC3R; MC4R) in kisspeptin neurons using RNAscope. Immunohistochemical analysis revealed that the majority of ARC kisspeptin neurons are contacted by presumptive AgRP terminals. RNAscope analysis revealed that nearly two thirds of the ARC kisspeptin neurons express mRNA for MC3R, while a small percentage (<10%) colocalize MC4R. Taken together, this data provides neuroanatomical evidence for a direct link between orexigenic AgRP neurons and reproductively critical kisspeptin neurons in the sheep, and builds upon our current understanding of the central link between energy balance and reproduction. Full article
(This article belongs to the Special Issue Neuroendocrine Control of Energy Metabolism)
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