Food-induced dopamine signaling in AgRP neurons promotes feeding

Zhang, Qi; Tang, Qijun; Purohit, Nidhi M.; Davenport, Julia B; Brennan, Charles D.; Patel, Rahul K.; Godschall, Elizabeth; Zwiefel, Larry S; Spano, Anthony; Campbell, John N.; Güler, Ali D.

doi:10.1016/j.celrep.2022.111718

Cited by 12 publications

(3 citation statements)

References 66 publications

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“…GLP-1 can directly stimulate hypothalamic POMC/CART anorexigenic neurons and indirectly inhibit neural projections of NPY and AgRP orexigenic neurons via gamma- aminobutyric acid (GABA) signaling to suppress appetite [42]. Interestingly, the two opposing appetiteregulating neural populations in the hypothalamus may directly or indirectly regulate the activity of VTA DA neurons through mediating signals of intermediate neurons such as GABAergic neurons to exert regulatory feeding effects [43][44][45][46]. In addition to homeostatic ingestion, the VTA has been suggested to be central in the ingestion reward system.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Alleviates Obesity and Insulin Resistance via the GLP-1-VTADA Reward Circuit

Zhu,

Tian,

Wei

et al. 2023

Neuroendocrinology

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Introduction: We investigated the effects of electroacupuncture (EA) on improving obesity and insulin resistance (IR) in high-fat diet-induced (HFDI) obese rats by modulating the nucleus tractus solitarius (NTS) glucagon-like peptide-1 (GLP-1)-ventral tegmental area (VTA) dopamine (DA) neural reward circuit, thereby uncovering a possible central mechanism underlying EA’s actions in improving obesity and IR. Methods: We randomly allocated 45 Wistar male rats to five groups (normal, model, EA, chemogenetic activation, chemogenetic suppression + EA), with 9 rats in each group. All interventions were conducted within 8 weeks after the model was established. We tested rats for obesity phenotypes included body mass, Lee’s index, 24-h food intake, and glucose-metabolism parameters. We observed protein and gene expression for GLP-1 in the NTS and tyrosine hydroxylase in the VTA by Western blotting and real-time polymerase chain reaction, as well as their localization by immunofluorescence. We also determined the DA content in the VTA using high-performance liquid chromatography. Results: Obese rats exhibited marked hyperphagia, accompanied by increased excitability of DA neurons in the VTA region and reduced insulin sensitivity. After EA treatment, obese rats showed augmented excitability of NTS GLP-1 and suppression of VTADA neurons with a diminution in food intake, showing results similar to those in the chemogenetic activation group. After EA treatment and while inhibiting GLP-1 neurons by chemogenetics, the effect of EA on activating GLP-1 neurons and inhibiting VTADA was partially abrogated. The effects of improving obesity and insulin sensitivity were likewise also suppressed. Conclusion: EA effectively activated GLP-1 neurons in the NTS, thereby inhibited the expression of DA in the VTA and improved obesity and insulin sensitivity in HFDI-obese rats.

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Section: Discussionmentioning

confidence: 99%

Electroacupuncture Alleviates Obesity and Insulin Resistance via the GLP-1-VTADA Reward Circuit

Zhu,

Tian,

Wei

et al. 2023

Neuroendocrinology

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“…Activation of AgRP neurons promotes feeding behaviour even under conditions of appetite suppression and decreases neural activity in the anorexigenic Parabrachial nucleus (PBN) [9]. Dopamine receptor D1 (Drd1) is also expressed on AgRP neurons, and upregulation of Drd1 activity induces the ingestion of high-fat and high-sugar foods [10]. Dynamin-related protein1 (Drpl), a key protein, mediates mitochondrial fission and fatty acid oxidation in AgRP neurons as an important mechanism for AgRP neurons to promote food intake [11].…”

Section: Arcuate Nucleus (Arc)mentioning

confidence: 99%

The Mechanism of the Gut-Brain Axis in Regulating Food Intake

Li,

Liu,

Cao

et al. 2023

Nutrients

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With the increasing prevalence of energy metabolism disorders such as diabetes, cardiovascular disease, obesity, and anorexia, the regulation of feeding has become the focus of global attention. The gastrointestinal tract is not only the site of food digestion and absorption but also contains a variety of appetite-regulating signals such as gut-brain peptides, short-chain fatty acids (SCFAs), bile acids (BAs), bacterial proteins, and cellular components produced by gut microbes. While the central nervous system (CNS), as the core of appetite regulation, can receive and integrate these appetite signals and send instructions to downstream effector organs to promote or inhibit the body’s feeding behaviour. This review will focus on the gut-brain axis mechanism of feeding behaviour, discussing how the peripheral appetite signal is sensed by the CNS via the gut-brain axis and the role of the central “first order neural nuclei” in the process of appetite regulation. Here, elucidation of the gut-brain axis mechanism of feeding regulation may provide new strategies for future production practises and the treatment of diseases such as anorexia and obesity.

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“…There are at least three contrasting ideas. The first is that the high-fat diets stimulate the hedonic system in the brain, and this overrides the normal homeostatic mechanisms that link together energy expenditure and intake [8,9]. This has been called hedonic eating [10,11], excessive hedonic drive [12], or hedonic overdrive [1].…”

Section: Introductionmentioning

confidence: 99%

The hedonic overdrive model best explains high‐fat diet‐induced obesity in C57BL/6 mice

Gao,

Hu,

Yang

et al. 2024

Obesity

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ObjectiveHigh‐fat diets cause obesity in male mice; however, the underlying mechanisms remain controversial. Here, three contrasting ideas were assessed: hedonic overdrive, reverse causality, and passive overconsumption models.MethodsA total of 12 groups of 20 individually housed 12‐week‐old C57BL/6 male mice were exposed to 12 high‐fat diets with varying fat content from 40% to 80% (by calories), protein content from 5% to 30%, and carbohydrate content from 8.4% to 40%. Body weight and food intake were monitored for 30 days after 7 days at baseline on a standard low‐fat diet.ResultsAfter exposure to the diets, energy intake increased first, and body weight followed later. Intake then declined. The peak energy intake was dependent on both dietary protein and carbohydrate, but not the dietary fat and energy density, whereas the rate of decrease in intake was only related to dietary protein. On high‐fat diets, the weight of food intake declined, but despite this average reduction of 14.4 g in food intake, they consumed, on average, 357 kJ more energy than at baseline.ConclusionsThe hedonic overdrive model fit the data best. The other two models were not supported.

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Food-induced dopamine signaling in AgRP neurons promotes feeding

Cited by 12 publications

References 66 publications

Electroacupuncture Alleviates Obesity and Insulin Resistance via the GLP-1-VTA<sup>DA</sup> Reward Circuit

Electroacupuncture Alleviates Obesity and Insulin Resistance via the GLP-1-VTA<sup>DA</sup> Reward Circuit

The Mechanism of the Gut-Brain Axis in Regulating Food Intake

The hedonic overdrive model best explains high‐fat diet‐induced obesity in C57BL/6 mice

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