Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre mice
Objective: The prevalence of obesity has increased over the past three decades. Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) play a vital role in induction of satiety. Chronic consumption of high-fat diet is known to reduce hypothalamic neuronal sensitivity to hormone...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Molecular Metabolism |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877824000358 |
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| author | Özge Başer Yavuz Yavuz Deniz Öykü Özen Hüseyin Buğra Özgün Sami Ağuş Cihan Civan Civaş Deniz Atasoy Bayram Yılmaz |
| author_facet | Özge Başer Yavuz Yavuz Deniz Öykü Özen Hüseyin Buğra Özgün Sami Ağuş Cihan Civan Civaş Deniz Atasoy Bayram Yılmaz |
| author_sort | Özge Başer |
| collection | DOAJ |
| description | Objective: The prevalence of obesity has increased over the past three decades. Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) play a vital role in induction of satiety. Chronic consumption of high-fat diet is known to reduce hypothalamic neuronal sensitivity to hormones like leptin, thus contributing to the development and persistence of obesity. The functional and morphological effects of a high-calorie diet on POMC neurons and how these effects contribute to the development and maintenance of the obese phenotype are not fully understood. For this purpose, POMC-Cre transgenic mice model was exposed to high-fat diet (HFD) and at the end of a 3- and 6-month period, electrophysiological and morphological changes, and the role of POMC neurons in homeostatic nutrition and their response to leptin were thoroughly investigated. Methods: Effects of HFD on POMC-satiety neurons in transgenic mice models exposed to chronic high-fat diet were investigated using electrophysiological (patch-clamp), chemogenetic and Cre recombinase advanced technological methods. Leptin, glucose and lipid profiles were determined and analyzed. Results: In mice exposed to a high-fat diet for 6 months, no significant changes in POMC dendritic spine number or projection density from POMC neurons to the paraventricular hypothalamus (PVN), lateral hypothalamus (LH), and bed nucleus stria terminalis (BNST) were observed. It was revealed that leptin hormone did not change the electrophysiological activities of POMC neurons in mice fed with HFD for 6 months. In addition, chemogenetic stimulation of POMC neurons increased HFD consumption. In the 3-month HFD-fed group, POMC activation induced an orexigenic response in mice, whereas switching to a standard diet was found to abolish orexigenic behavior in POMC mice. Conclusions: Chronic high fat consumption disrupts the regulation of POMC neuron activation by leptin. Altered POMC neuron activation abolished the neuron's characteristic behavioral anorexigenic response. Change in nutritional content contributes to the reorganization of developing maladaptations. |
| first_indexed | 2024-03-07T19:09:54Z |
| format | Article |
| id | doaj.art-f679729fb74142528d8befff8a057806 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-24T16:26:22Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-f679729fb74142528d8befff8a0578062024-03-31T04:37:19ZengElsevierMolecular Metabolism2212-87782024-04-0182101904Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre miceÖzge Başer0Yavuz Yavuz1Deniz Öykü Özen2Hüseyin Buğra Özgün3Sami Ağuş4Cihan Civan Civaş5Deniz Atasoy6Bayram Yılmaz7Yeditepe University, Faculty of Medicine, Department of Physiology, Istanbul, TürkiyeYeditepe University, Faculty of Medicine, Department of Physiology, Istanbul, TürkiyeYeditepe University, Faculty of Medicine, Department of Physiology, Istanbul, TürkiyeYeditepe University, Faculty of Medicine, Department of Physiology, Istanbul, TürkiyeYeditepe University, Faculty of Medicine, Department of Physiology, Istanbul, TürkiyeYeditepe University, Faculty of Medicine, Department of Physiology, Istanbul, TürkiyeUniversity of Iowa, Carver College of Medicine, Department of Neuroscience and Pharmacology, Iowa City, USAYeditepe University, Faculty of Medicine, Department of Physiology, Istanbul, Türkiye; Izmir Biomedicine and Genome Center, Izmir, Türkiye; Corresponding author. Yeditepe University, Faculty of Medicine, Department of Physiology, Istanbul, Türkiye.Objective: The prevalence of obesity has increased over the past three decades. Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) play a vital role in induction of satiety. Chronic consumption of high-fat diet is known to reduce hypothalamic neuronal sensitivity to hormones like leptin, thus contributing to the development and persistence of obesity. The functional and morphological effects of a high-calorie diet on POMC neurons and how these effects contribute to the development and maintenance of the obese phenotype are not fully understood. For this purpose, POMC-Cre transgenic mice model was exposed to high-fat diet (HFD) and at the end of a 3- and 6-month period, electrophysiological and morphological changes, and the role of POMC neurons in homeostatic nutrition and their response to leptin were thoroughly investigated. Methods: Effects of HFD on POMC-satiety neurons in transgenic mice models exposed to chronic high-fat diet were investigated using electrophysiological (patch-clamp), chemogenetic and Cre recombinase advanced technological methods. Leptin, glucose and lipid profiles were determined and analyzed. Results: In mice exposed to a high-fat diet for 6 months, no significant changes in POMC dendritic spine number or projection density from POMC neurons to the paraventricular hypothalamus (PVN), lateral hypothalamus (LH), and bed nucleus stria terminalis (BNST) were observed. It was revealed that leptin hormone did not change the electrophysiological activities of POMC neurons in mice fed with HFD for 6 months. In addition, chemogenetic stimulation of POMC neurons increased HFD consumption. In the 3-month HFD-fed group, POMC activation induced an orexigenic response in mice, whereas switching to a standard diet was found to abolish orexigenic behavior in POMC mice. Conclusions: Chronic high fat consumption disrupts the regulation of POMC neuron activation by leptin. Altered POMC neuron activation abolished the neuron's characteristic behavioral anorexigenic response. Change in nutritional content contributes to the reorganization of developing maladaptations.http://www.sciencedirect.com/science/article/pii/S2212877824000358ObesityPOMC neuronsElectrophysiologyChemogeneticHigh fat dietBehavioral |
| spellingShingle | Özge Başer Yavuz Yavuz Deniz Öykü Özen Hüseyin Buğra Özgün Sami Ağuş Cihan Civan Civaş Deniz Atasoy Bayram Yılmaz Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre mice Molecular Metabolism Obesity POMC neurons Electrophysiology Chemogenetic High fat diet Behavioral |
| title | Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre mice |
| title_full | Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre mice |
| title_fullStr | Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre mice |
| title_full_unstemmed | Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre mice |
| title_short | Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre mice |
| title_sort | effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in pomc cre mice |
| topic | Obesity POMC neurons Electrophysiology Chemogenetic High fat diet Behavioral |
| url | http://www.sciencedirect.com/science/article/pii/S2212877824000358 |
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