Ingested non-essential amino acids recruit brain orexin cells to suppress eating in mice

Viskaitis, Paulius; Arnold, Myrtha; Garau, Celia; Jensen, Lise Torp; Fugger, Lars; Peleg‐Raibstein, Daria; Burdakov, Denis

doi:10.1016/j.cub.2022.02.067

Cited by 30 publications

(43 citation statements)

References 57 publications

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“…The unprecedented simultaneous real-time measurements of blood glucose and HON dynamics reported here reveal unforeseen complexity of HON activity patterns inside the living organism. Concurrently with the realization that HONs t rapidly alter vital behaviors (Giardino et al, 2018; Karnani et al, 2020; Sakurai, 2014; Viskaitis et al, 2022), much work focused on external stimuli controlling their activity in vivo . This revealed that HON activity is acutely regulated by diverse external stimuli at the time scale of milliseconds (Gonzalez et al, 2016a; Hassani et al, 2016; Karnani et al, 2020; Mileykovskiy et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Together, these observations indicate that HONs are essential for glucose-induced control of running. It is tempting to speculate that this evolved to prevent moving away from food (Viskaitis et al, 2022), and/or to reduce movement-related energy use, when blood glucose is rising thus facilitating body energy repletion. From this perspective, it is interesting that glucose-induced running suppression can be overridden by selective HON activation (Figure 5F-J), because physiologically HONs are activated by diverse salient signals, such as those indicative of stress or reward (Gonzalez et al, 2016a; Hassani et al, 2016; Karnani et al, 2020; Peleg-Raibstein and Burdakov, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Implants and a custom-made aluminum head plate were secured to the skull using three skull screws and dental cement (Kem-dent and C&B-Metabond). For intragastric infusion experiments, the surgery was adapted from rats as previously described (39). A custommade catheter was implanted by guiding tubing subcutaneously through the dorsal to the ventral incision.…”

Section: Methodsmentioning

confidence: 99%

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Orexin cells efficiently decode blood glucose dynamics to drive adaptive behavior

Viskaitis

Tesmer

Karnani

et al. 2022

Preprint

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The brain needs to track body energy state to optimize physiology and behavior. Important information about current and future energy states is contained in minute-to-minute fluctuations in blood glucose. However, it is unclear whether brain glucose sensors are capable of responding to this temporal structure to extract such information. In behaving mammals, hypothalamic hypocretin/orexin neurons (HONs) control arousal and are proposed to sense energy balance, yet recent studies show that HON activity varies rapidly (over seconds) with locomotion. It remains unknown if and how HONs reflect blood glucose fluctuations. Here, for the first time, we co-monitored HON activity and blood glucose in behaving mice, uncovering inhibition of HONs by rising blood glucose. Surprisingly, peak HON signals (population waves) anticipated peak glucose deviations by several minutes. In multivariate analysis of diverse HON activity correlates (locomotion, metabolic variables), the glucose temporal gradient (negative first derivative) emerged as prime predictor of HON population activity on the minute timescales, thereby explaining this anticipatory response. Furthermore, 2-photon imaging of >900 individual HONs revealed parallel communication of absolute blood glucose values and their derivatives in distinct HON subsets. Thus, HONs transmit multiplexed slowly and rapidly changing information, and, in the slow bandwidth, extract temporal features from blood glucose dynamics that suggest a hybrid of anticipatory and proportional logic in brain responses to blood glucose.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Orexin cells efficiently decode blood glucose dynamics to drive adaptive behavior

Viskaitis

Tesmer

Karnani

et al. 2022

Preprint

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“… 228 Interestingly, the supplement with non-essential amino acids results in appetitive suppression through direct activation of hypothalamic orexin/hypocretin neurons. 229 …”

Section: Nutrient-associated Molecular Mechanismsmentioning

confidence: 99%

Dietary regulation in health and disease

Gao

et al. 2022

Sig Transduct Target Ther

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Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials have demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan and delaying ageing in various species such as yeast, drosophila, rodent, primate and human. It emerges to develop the precision-nutrition therapeutics to slow age-related biological processes and treat diverse diseases. However, the nutritive advantages frequently diversify among individuals as well as organs and tissues, which brings challenges in this field. In this review, we summarize the different forms of dietary interventions extensively prescribed for healthspan improvement and disease treatment in pre-clinical or clinical. We discuss the nutrient-mediated mechanisms including metabolic regulators, nutritive metabolism pathways, epigenetic mechanisms and circadian clocks. Comparably, we describe diet-responsive effectors by which dietary interventions influence the endocrinic, immunological, microbial and neural states responsible for improving health and preventing multiple diseases in humans. Furthermore, we expatiate diverse patterns of dietotheroapies, including different fasting, calorie-restricted diet, ketogenic diet, high-fibre diet, plants-based diet, protein restriction diet or diet with specific reduction in amino acids or microelements, potentially affecting the health and morbid states. Altogether, we emphasize the profound nutritional therapy, and highlight the crosstalk among explored mechanisms and critical factors to develop individualized therapeutic approaches and predictors.

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“…Apart from AgRP and POMC neurons, other populations in the hypothalamus also contribute to appetite regulation, including a subset of nucleus of the solitary tract neurons containing cholecystokinin (CCK NTS ) ( 70 ), glutamatergic neurons projecting to PVH in the medial septal complex (MSc) ( 71 ), tachykinin-1 expressing neurons (PSTN Tac1 ) in the parasubthalamic nucleus ( 72 ), steroidogenic factor 1 (SF1) neurons in the ventromedial hypothalamus ( 73 ), and melanin-concentrating hormone-expressing neurons ( 74 ). In addition, progress has also been made in some known appetite-regulating factors like neuropeptide Y (NPY) and orexin with optogenetics ( 75 , 76 ). Many other brain regions are also discovered to engage in appetite change in both clinical and basic experiments ( 77 – 80 ).…”

Section: Optogenetic Findings In Depressive-like Behaviorsmentioning

confidence: 99%

Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms

Shi

Du²,

Xia³

et al. 2022

Front. Psychiatry

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BackgroundsThe neural circuit mechanisms underlying depression remain unclear. Recently optogenetics has gradually gained recognition as a novel technique to regulate the activity of neurons with light stimulation. Scientists are now transferring their focus to the function of brain regions and neural circuits in the pathogenic progress of depression. Deciphering the circuitry mechanism of depressive-like behaviors may help us better understand the symptomatology of depression. However, few studies have summarized current progress on optogenetic researches into the neural circuit mechanisms of depressive-like behaviors.AimsThis review aimed to introduce fundamental characteristics and methodologies of optogenetics, as well as how this technique achieves specific neuronal control with spatial and temporal accuracy. We mainly summarized recent progress in neural circuit discoveries in depressive-like behaviors using optogenetics and exhibited the potential of optogenetics as a tool to investigate the mechanism and possible optimization underlying antidepressant treatment such as ketamine and deep brain stimulation.MethodsA systematic review of the literature published in English mainly from 2010 to the present in databases was performed. The selected literature is then categorized and summarized according to their neural circuits and depressive-like behaviors.ConclusionsMany important discoveries have been made utilizing optogenetics. These findings support optogenetics as a powerful and potential tool for studying depression. And our comprehension to the etiology of depression and other psychiatric disorders will also be more thorough with this rapidly developing technique in the near future.

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Ingested non-essential amino acids recruit brain orexin cells to suppress eating in mice

Cited by 30 publications

References 57 publications

Orexin cells efficiently decode blood glucose dynamics to drive adaptive behavior

Orexin cells efficiently decode blood glucose dynamics to drive adaptive behavior

Dietary regulation in health and disease

Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms

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