A synaptic amplifier of hunger for regaining body weight in the hypothalamus

Grzelka, Katarzyna; Wilhelms, Hannah; Dodt, Stephan; Dreisow, Marie-Luise; Madara, Joseph C.; Walker, Samuel J; Wu, Chen; Wang, Daqing; Lowell, Bradford B.; Fenselau, Henning

doi:10.1016/j.cmet.2023.03.002

Cited by 33 publications

(12 citation statements)

References 81 publications

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“…The results of the gene set enrichment analysis (GSEA) showed that after ZEN treatment, glutaminergic synapse was significantly downregulated ( P < 0.05) in females and males (Figure D,E). Glutaminergic synapse is closely related to feeding regulation . The results of a correlation analysis between the core differentially expressed genes of female and male groups and FXR showed that the expression levels of FXR were negatively correlated with most of the core differentially expressed genes (Figure F,G), which suggested that FXR regulates the feeding behavior by modulating the glutaminergic synapse.…”

Section: Resultsmentioning

confidence: 92%

“…To determine the regulatory role of FXR in the hypothalamus, we conducted transcriptome analysis of the hypothalamus and found that the glutamatergic synapse in the hypothalamus was significantly downregulated after ZEN treatment, which suggested that ZEN impaired the signal transduction pathways and reduced food intake. 31 The expression levels of FXR were correlated with most of the core genes of the glutamatergic synapse. These results suggested that ZEN activated hypothalamic FXR expression by altering the composition of BAs and that hypothalamic FXR may exert its effects via the glutamatergic synapse to reduce food intake.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Moreover, the expression levels of hypothalamic FXR were positively correlated with GCDCA and negatively correlated with C/U BAs, which confirmed that ZEN-induced changes in BAs could activate hypothalamic FXR. To determine the regulatory role of FXR in the hypothalamus, we conducted transcriptome analysis of the hypothalamus and found that the glutamatergic synapse in the hypothalamus was significantly downregulated after ZEN treatment, which suggested that ZEN impaired the signal transduction pathways and reduced food intake . The expression levels of FXR were correlated with most of the core genes of the glutamatergic synapse.…”

Section: Discussionmentioning

confidence: 99%

“…Glutaminergic synapse is closely related to feeding regulation. 31 The results of a correlation analysis between the core differentially expressed genes of female and male groups and FXR showed that the expression levels of FXR were negatively correlated with most of the core differentially expressed genes (Figure 4F,G), which suggested that FXR regulates the feeding behavior by modulating the glutaminergic synapse. The results of the GSEA analysis also showed that the chemokine signaling pathway was inhibited (P < 0.05) after ZEN treatment (Figure 4H,I), which probably interacted with glutaminergic synapse to regulate feeding.…”

Section: Zen Altered the Expression Levels Of Key Genes And Proteins ...mentioning

confidence: 94%

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Zearalenone Decreases Food Intake by Disrupting the Gut–Liver–Hypothalamus Axis Signaling via Bile Acids

Yuan,

Ma,

et al. 2024

J. Agric. Food Chem.

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Zearalenone (ZEN) is a mycotoxin that is harmful to humans and animals. In this study, female and male rats were exposed to ZEN, and the results showed that ZEN reduced the farnesoid X receptor (FXR) expression levels in the liver and disrupted the enterohepatic circulation of bile acids (BAs). A decrease in food intake induced by ZEN was negatively correlated with an increase in the level of total BAs. BA-targeted metabolomics revealed that ZEN increased glycochenodeoxycholic acid levels and decreased the ratio of conjugated BAs to unconjugated BAs, which further increased the hypothalamic FXR expression levels. Preventing the increase in total BA levels induced by ZEN via Lactobacillus rhamnosus GG intervention restored the appetite. In conclusion, ZEN disrupted the enterohepatic circulation of BAs to decrease the level of food intake. This study reveals a possible mechanism by which ZEN affects food intake and provides a new approach to decrease the toxic effects of ZEN.

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Section: Resultsmentioning

confidence: 92%

Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Zen Altered the Expression Levels Of Key Genes And Proteins ...mentioning

confidence: 94%

See 2 more Smart Citations

Zearalenone Decreases Food Intake by Disrupting the Gut–Liver–Hypothalamus Axis Signaling via Bile Acids

Yuan,

Ma,

et al. 2024

J. Agric. Food Chem.

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“…Importantly, fasting reduced the strength of the VMH excitatory input to POMC cells, consistent with the ascribed role of the VMH as a satiety center containing primarily glutamatergic neurons. Another study showed that some of the plastic glutamatergic input onto AgRP neurons increased in response to energy deficit is provided by TRH/PACAP + cells in the PVN (Grzelka et al, 2023).…”

Section: Synaptic Remodeling In Metabolic Circuits In the Adult Hypot...mentioning

confidence: 99%

Synaptic plasticity and the role of astrocytes in central metabolic circuits

Ameroso,

Rios

2023

WIREs Mechanisms of Disease

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Neural circuits in the brain, primarily in the hypothalamus, are paramount to the homeostatic control of feeding and energy utilization. They integrate hunger, satiety, and body adiposity cues from the periphery and mediate the appropriate behavioral and physiological responses to satisfy the energy demands of the animal. Notably, perturbations in central homeostatic circuits have been linked to the etiology of excessive feeding and obesity. Considering the ever‐changing energy requirements of the animal and required adaptations, it is not surprising that brain‐feeding circuits remain plastic in adulthood and are subject to changes in synaptic strength as a consequence of nutritional status. Indeed, synapse density, probability of presynaptic transmitter release, and postsynaptic responses in hypothalamic energy balance centers are tailored to behavioral and physiological responses required to sustain survival. Mounting evidence supports key roles of astrocytes facilitating some of this plasticity. Here we discuss these synaptic plasticity mechanisms and the emerging roles of astrocytes influencing energy and glucose balance control in health and disease.This article is categorized under: Cancer > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology

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Obesity‐ and diet‐induced plasticity in systems that control eating and energy balance

Ferrario,

Münzberg‐Gruening,

Rinaman

et al. 2024

Obesity

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In April 2023, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in partnership with the National Institute of Child Health and Human Development, the National Institute on Aging, and the Office of Behavioral and Social Sciences Research, hosted a 2‐day online workshop to discuss neural plasticity in energy homeostasis and obesity. The goal was to provide a broad view of current knowledge while identifying research questions and challenges regarding neural systems that control food intake and energy balance. This review includes highlights from the meeting and is intended both to introduce unfamiliar audiences with concepts central to energy homeostasis, feeding, and obesity and to highlight up‐and‐coming research in these areas that may be of special interest to those with a background in these fields. The overarching theme of this review addresses plasticity within the central and peripheral nervous systems that regulates and influences eating, emphasizing distinctions between healthy and disease states. This is by no means a comprehensive review because this is a broad and rapidly developing area. However, we have pointed out relevant reviews and primary articles throughout, as well as gaps in current understanding and opportunities for developments in the field.

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A synaptic amplifier of hunger for regaining body weight in the hypothalamus

Cited by 33 publications

References 81 publications

Zearalenone Decreases Food Intake by Disrupting the Gut–Liver–Hypothalamus Axis Signaling via Bile Acids

Zearalenone Decreases Food Intake by Disrupting the Gut–Liver–Hypothalamus Axis Signaling via Bile Acids

Synaptic plasticity and the role of astrocytes in central metabolic circuits

Obesity‐ and diet‐induced plasticity in systems that control eating and energy balance

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