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Special Issue "Hypothalamic Regulation of Obesity"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 April 2021).

Special Issue Editors

Dr. Rosalía Rodríguez-Rodríguez
E-Mail Website
Guest Editor
Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, E-08195 Sant Cugat del Vallès, Spain
Interests: obesity; hypothalamus; metabolic syndrome; vascular function; endocannabinoids
Special Issues and Collections in MDPI journals
Dr. Cristina Miralpeix
E-Mail Website
Guest Editor
INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France
Interests: obesity; hypothalamic neurons; CB1R

Special Issue Information

Dear Colleagues,

The obesity epidemic represents a major socioeconomic problem that urgently requires a better understanding of the mechanisms mediating the imbalance between food intake and energy expenditure and of obesity-related metabolic and cardiovascular complications. Gaining insight into the cellular basis of obesity could lay the foundations for the development of new therapeutic strategies.

In the last few decades, it has been strongly demonstrated that the hypothalamus is the critical brain region regulating energy homeostasis. The hypothalamus contains hormonal- and nutrient-sensing nuclei that organize central and peripheral responses for maintaining normal body weight, food intake, energy expenditure and nutrient partitioning. Within the hypothalamus, numerous specialized neuronal populations are connected to each other and also to various extrahypothalamic brain regions to coordinate energy homeostasis. Evidence also suggests the participation of non-neuronal populations, such as astrocytes, or even the interesting interplay between astrocytes and hypothalamic neurons, whose disruption leads to insulin resistance and obesity.

This Special Issue will report on the most recent insights into the hypothalamic neuronal and non-neuronal pathways involved in obesity development. Novel findings related to key systems, such as endocannabinoid and melanocortin-related pathways, in the hypothalamus will be discussed. In addition, the emerging contribution of the cross-talk between the hypothalamus and peripheral tissues, such as gut and adipose tissue, in obesity will be a promising topic to deal with. Therefore, here we will present an overview of the most recent mechanisms underlying the hypothalamic regulation of obesity and the impact of these investigations in the prevention and treatment of human obesity.

Dr. Rosalía Rodríguez-Rodríguez
Guest Editor

Manuscript Submission Information

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Keywords

  • obesity
  • food intake
  • energy expenditure
  • hypothalamus
  • energy homeostasis
  • neurons
  • astrocytes
  • insulin resistance
  • glucose homeostasis
  • lipid metabolism
  • adipose tissue
  • gut-brain axis

Published Papers (6 papers)

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Research

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Open AccessArticle
Effects of Overexpression of Neurosecretory Protein GL-Precursor Gene on Glucose Homeostasis and Insulin Sensitivity in Mice
Int. J. Mol. Sci. 2021, 22(9), 4681; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094681 - 28 Apr 2021
Viewed by 184
Abstract
A high-fat diet (HFD) quickly induces obesity with insulin resistance and hyperglycemia. We previously reported that a novel hypothalamic small protein, named neurosecretory protein GL (NPGL), stimulates feeding and fat accumulation in mice. However, the effects of NPGL on insulin sensitivity and glucose [...] Read more.
A high-fat diet (HFD) quickly induces obesity with insulin resistance and hyperglycemia. We previously reported that a novel hypothalamic small protein, named neurosecretory protein GL (NPGL), stimulates feeding and fat accumulation in mice. However, the effects of NPGL on insulin sensitivity and glucose homeostasis remain unknown. Hence, we subjected NPGL-precursor gene (Npgl)-overexpressing mice to the oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) under normal chow (NC) and HFD conditions. Npgl overexpression promoted body mass gain and tended to increase food intake of NC-fed mice, whereas it had little effect on HFD-fed mice. The OGTT showed elevated blood glucose and insulin levels in Npgl-overexpressing NC-fed mice 15 min after glucose administration. Both the OGTT and IPITT demonstrated that Npgl overexpression decreased blood glucose levels in HFD-fed mice 60 min after glucose and insulin treatments. Notably, Npgl overexpression increased adipose tissue masses only in NC-fed mice, and it decreased blood glucose and insulin levels in HFD-fed mice at the experimental end point. It also increased the mRNA expression of galanin, one of the feeding and metabolic regulatory neuropeptides, in the hypothalamus of HFD-fed mice. Therefore, NPGL may alleviate HFD-induced hyperglycemia and insulin resistance in mice. Full article
(This article belongs to the Special Issue Hypothalamic Regulation of Obesity)
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Open AccessArticle
Angiopoietin-Like Growth Factor Involved in Leptin Signaling in the Hypothalamus
Int. J. Mol. Sci. 2021, 22(7), 3443; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073443 - 26 Mar 2021
Viewed by 359
Abstract
The hypothalamic regulation of appetite governs whole-body energy balance. Satiety is regulated by endocrine factors including leptin, and impaired leptin signaling is associated with obesity. Despite the anorectic effect of leptin through the regulation of the hypothalamic feeding circuit, a distinct downstream mediator [...] Read more.
The hypothalamic regulation of appetite governs whole-body energy balance. Satiety is regulated by endocrine factors including leptin, and impaired leptin signaling is associated with obesity. Despite the anorectic effect of leptin through the regulation of the hypothalamic feeding circuit, a distinct downstream mediator of leptin signaling in neuron remains unclear. Angiopoietin-like growth factor (AGF) is a peripheral activator of energy expenditure and antagonizes obesity. However, the regulation of AGF expression in brain and localization to mediate anorectic signaling is unknown. Here, we demonstrated that AGF is expressed in proopiomelanocortin (POMC)-expressing neurons located in the arcuate nucleus (ARC) of the hypothalamus. Unlike other brain regions, hypothalamic AGF expression is stimulated by leptin-induced signal transducers and activators of transcription 3 (STAT3) phosphorylation. In addition, leptin treatment to hypothalamic N1 cells significantly enhanced the promoter activity of AGF. This induction was abolished by the pretreatment of ruxolitinib, a leptin signaling inhibitor. These results indicate that hypothalamic AGF expression is induced by leptin and colocalized to POMC neurons. Full article
(This article belongs to the Special Issue Hypothalamic Regulation of Obesity)
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Open AccessArticle
Adiponectin Controls Nutrient Availability in Hypothalamic Astrocytes
Int. J. Mol. Sci. 2021, 22(4), 1587; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041587 - 04 Feb 2021
Cited by 1 | Viewed by 566
Abstract
Adiponectin, an adipose tissue-derived hormone, plays integral roles in lipid and glucose metabolism in peripheral tissues, such as the skeletal muscle, adipose tissue, and liver. Moreover, it has also been shown to have an impact on metabolic processes in the central nervous system. [...] Read more.
Adiponectin, an adipose tissue-derived hormone, plays integral roles in lipid and glucose metabolism in peripheral tissues, such as the skeletal muscle, adipose tissue, and liver. Moreover, it has also been shown to have an impact on metabolic processes in the central nervous system. Astrocytes comprise the most abundant cell type in the central nervous system and actively participate in metabolic processes between blood vessels and neurons. However, the ability of adiponectin to control nutrient metabolism in astrocytes has not yet been fully elucidated. In this study, we investigated the effects of adiponectin on multiple metabolic processes in hypothalamic astrocytes. Adiponectin enhanced glucose uptake, glycolytic processes and fatty acid oxidation in cultured primary hypothalamic astrocytes. In line with these findings, we also found that adiponectin treatment effectively enhanced synthesis and release of monocarboxylates. Overall, these data suggested that adiponectin triggers catabolic processes in astrocytes, thereby enhancing nutrient availability in the hypothalamus. Full article
(This article belongs to the Special Issue Hypothalamic Regulation of Obesity)
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Review

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Open AccessReview
Adaptive Changes in the Central Control of Energy Homeostasis Occur in Response to Variations in Energy Status
Int. J. Mol. Sci. 2021, 22(5), 2728; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052728 - 08 Mar 2021
Viewed by 614
Abstract
Energy homeostasis is regulated in coordinate fashion by the brain-gut axis, the homeostatic energy balance circuitry in the hypothalamus and the hedonic energy balance circuitry comprising the mesolimbcortical A10 dopamine pathway. Collectively, these systems convey and integrate information regarding nutrient status and [...] Read more.
Energy homeostasis is regulated in coordinate fashion by the brain-gut axis, the homeostatic energy balance circuitry in the hypothalamus and the hedonic energy balance circuitry comprising the mesolimbcortical A10 dopamine pathway. Collectively, these systems convey and integrate information regarding nutrient status and the rewarding properties of ingested food, and formulate it into a behavioral response that attempts to balance fluctuations in consumption and food-seeking behavior. In this review we start with a functional overview of the homeostatic and hedonic energy balance circuitries; identifying the salient neural, hormonal and humoral components involved. We then delve into how the function of these circuits differs in males and females. Finally, we turn our attention to the ever-emerging roles of nociceptin/orphanin FQ (N/OFQ) and pituitary adenylate cyclase-activating polypeptide (PACAP)—two neuropeptides that have garnered increased recognition for their regulatory impact in energy homeostasis—to further probe how the imposed regulation of energy balance circuitry by these peptides is affected by sex and altered under positive (e.g., obesity) and negative (e.g., fasting) energy balance states. It is hoped that this work will impart a newfound appreciation for the intricate regulatory processes that govern energy homeostasis, as well as how recent insights into the N/OFQ and PACAP systems can be leveraged in the treatment of conditions ranging from obesity to anorexia. Full article
(This article belongs to the Special Issue Hypothalamic Regulation of Obesity)
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Open AccessReview
Hypothalamic Microglial Heterogeneity and Signature under High Fat Diet–Induced Inflammation
Int. J. Mol. Sci. 2021, 22(5), 2256; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052256 - 24 Feb 2021
Viewed by 622
Abstract
Under high-fat feeding, the hypothalamus atypically undergoes pro-inflammatory signaling activation. Recent data from transcriptomic analysis of microglia from rodents and humans has allowed the identification of several microglial subpopulations throughout the brain. Numerous studies have clarified the roles of these cells in hypothalamic [...] Read more.
Under high-fat feeding, the hypothalamus atypically undergoes pro-inflammatory signaling activation. Recent data from transcriptomic analysis of microglia from rodents and humans has allowed the identification of several microglial subpopulations throughout the brain. Numerous studies have clarified the roles of these cells in hypothalamic inflammation, but how each microglial subset plays its functions upon inflammatory stimuli remains unexplored. Fortunately, these data unveiling microglial heterogeneity have triggered the development of novel experimental models for studying the roles and characteristics of each microglial subtype. In this review, we explore microglial heterogeneity in the hypothalamus and their crosstalk with astrocytes under high fat diet–induced inflammation. We present novel currently available ex vivo and in vivo experimental models that can be useful when designing a new research project in this field of study. Last, we examine the transcriptomic data already published to identify how the hypothalamic microglial signature changes upon short-term and prolonged high-fat feeding. Full article
(This article belongs to the Special Issue Hypothalamic Regulation of Obesity)
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Open AccessReview
Hypothalamic Actions of SIRT1 and SIRT6 on Energy Balance
Int. J. Mol. Sci. 2021, 22(3), 1430; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031430 - 31 Jan 2021
Viewed by 696
Abstract
Sirtuins are NAD+ dependent deacetylases that regulate a large number of physiological processes. These enzymes are highly conserved and act as energy sensors to coordinate different metabolic responses in a controlled manner. At present, seven mammalian sirtuins (SIRT 1-7) have been identified, with [...] Read more.
Sirtuins are NAD+ dependent deacetylases that regulate a large number of physiological processes. These enzymes are highly conserved and act as energy sensors to coordinate different metabolic responses in a controlled manner. At present, seven mammalian sirtuins (SIRT 1-7) have been identified, with SIRT1 and SIRT6 shown to exert their metabolic actions in the hypothalamus, both with crucial roles in eliciting responses to dampen metabolic complications associated with obesity. Therefore, our aim is to compile the current understanding on the role of SIRT1 and SIRT6 in the hypothalamus, especially highlighting their actions on the control of energy balance. Full article
(This article belongs to the Special Issue Hypothalamic Regulation of Obesity)
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