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Article
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Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons
SHLP2 is a mitochondrial-derived peptide that plays an important role in energy homeostasis. Here, the authors show SHLP2’s protective effect against obesity and its mechanisms of action by binding to CXCR7 and activating hypothalamic neurons that regulate food intake, energy expenditure, and glucose homeostasis.
- Seul Ki Kim
- , Le Trung Tran
- & Ki Woo Kim
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Article
| Open Access
Spectro-spatial features in distributed human intracranial activity proactively encode peripheral metabolic activity
How human brain activity relates to peripheral metabolism is not known. Here, the authors find that intracranial activity is strongly coupled to peripheral glucose variations across multiple brain regions and is sufficient for decoding of glucose levels.
- Yuhao Huang
- , Jeffrey B. Wang
- & Casey H. Halpern
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Article
| Open Access
The melanocortin action is biased toward protection from weight loss in mice
Melanocortin action is known to regulate body weight. Here the authors report that while inhibition of the hypothalamic melanocortin action leads to obesity in mice, chronic activation of melanocortin action is not sufficient to cause weight loss.
- Hongli Li
- , Yuanzhong Xu
- & Qingchun Tong
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Article
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Hypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes in rats
Food intake is determined by learned appetitive responses and physiological “appetition” signals after eating begins. Here, authors show melanin-concentrating hormone (MCH)-producing neurons integrate these processes to promote caloric intake.
- Keshav S. Subramanian
- , Logan Tierno Lauer
- & Scott E. Kanoski
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Article
| Open Access
Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice
Eating behviours consist of seeking and consummatory phases. Here, authors show that two distinct lateral hypothalamic leptin receptor neurons orchestrate seeking and consummatory phases of eating behaviour via hunger signal, Neuropeptide Y.
- Young Hee Lee
- , Yu-Been Kim
- & Hyung Jin Choi
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Article
| Open Access
Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models
Time-restricted feeding (TRF) can prevent muscle function decline from obesogenic challenges. Here, the authors reveal that TRF improves muscle function through modulations of common and distinct pathways in diet- and genetic-induced obesity models.
- Christopher Livelo
- , Yiming Guo
- & Girish C. Melkani
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Article
| Open Access
A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity
Although diet modulates aging, little is known about whether and how nutrient regulates longevity. Here, the authors show that glucose-restricted diets prolong longevity through series of conserved factors, such as neuronal AMPK, neuropeptide, AdipoR, PPARα, and Δ9 desaturases by promoting membrane fluidity.
- Jin-Hyuck Jeong
- , Jun-Seok Han
- & Eun-Soo Kwon
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Article
| Open Access
Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice
Feeding and stress are deeply related to each other, yet neural circuits how they interact are not fully understood. Here, the authors show that the parabrachial-to-parasubthalamic nucleus pathway is involved in fear-induced feeding suppression.
- Takashi Nagashima
- , Suguru Tohyama
- & Ayako M. Watabe
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Article
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Continuous cholinergic-dopaminergic updating in the nucleus accumbens underlies approaches to reward-predicting cues
Nucleus accumbens cholinergic interneurons release acetylcholine and glutamate. Here, authors show that acetylcholine, rather than glutamate, is predominantly involved in updating dopamine dynamics mediating Pavlovian approach behaviours.
- Miguel Skirzewski
- , Oren Princz-Lebel
- & Timothy J. Bussey
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Article
| Open Access
Hedgehog-mediated gut-taste neuron axis controls sweet perception in Drosophila
Food regulates taste perception, but the underlying molecular mechanisms are not clear. Here, the authors reveal that sugar intake in Drosophila induces the gut to secrete Hedgehog into the circulation that suppresses sweet taste, sugar perception and preference.
- Yunpo Zhao
- , Mohammed A. Khallaf
- & Mattias Alenius
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Article
| Open Access
Adipocytes control food intake and weight regain via Vacuolar-type H+ ATPase
Energy metabolism is dysregulated in obesity, and some if these changes persist after weight loss and may contribute to weight regain. Here the authors report that a vacuolar-type H+ ATPase, ATP6v0a1, is induced in adipocytes during obesity and persists after weight loss, and regulates food intake and weight gain in C. elegans and mice.
- Rizaldy C. Zapata
- , Maria Carretero
- & Olivia Osborn
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Article
| Open Access
A temperature-regulated circuit for feeding behavior
Feeding behavior is modulated by ambient temperature, as lower temperatures increase the necessity for energy intake and vice versa. Here the authors identify neuronal pathways that control feeding in a temperature-dependent manner.
- Shaowen Qian
- , Sumei Yan
- & Yi Zhou
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Article
| Open Access
Social isolation modulates appetite and avoidance behavior via a common oxytocinergic circuit in larval zebrafish
Social interactions are known to guide behaviour, but how different species represent social stimuli is poorly understood. In this study, the authors demonstrate how social cues in the larval zebrafish suppress an oxytocinergic circuit, which regulates avoidance and feeding behaviour.
- Caroline L. Wee
- , Erin Song
- & Samuel Kunes
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Article
| Open Access
Randomized controlled trial for time-restricted eating in healthy volunteers without obesity
Time-restricted eating, both early (eTRF) and mid-day (mTRF), have been shown to have metabolic benefits. Here the authors report a randomized controlled trial to compare the effects of eTRF and mTRF in healthy volunteers without obesity, and find that eTRF is more effective in improving the primary outcome insulin sensitivity.
- Zhibo Xie
- , Yuning Sun
- & Yilei Mao
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Article
| Open Access
The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress
Intestinal nutrient-sensing is important in metabolic control. Here the authors show that the gut-derived hormone Allatostatin C, a somatostatin homolog in fruit flies, links enteric nutrient sensing to behavioral and metabolic adaptations that maintain energetic homeostasis in Drosophila melanogaster.
- Olga Kubrak
- , Takashi Koyama
- & Kim Rewitz
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Article
| Open Access
Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
Visceral adipose tissue secretes cytokines to regulate the homeostasis of organs. Here, the authors show that epididymal white adipose tissue-secreted osteopontin induces lipophagocytic mobilization of macrophages and promotes bone matrix degradation via activating osteoclasts.
- Bingyang Dai
- , Jiankun Xu
- & Ling Qin
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Article
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Synchronization between peripheral circadian clock and feeding-fasting cycles in microfluidic device sustains oscillatory pattern of transcriptome
Chronic desynchronization between physiological and behavioral rhythms has been linked to the onset of metabolic diseases. Here the authors control the cyclic metabolic signals in a microfluidic device to study the effects of the timing, period and frequency of glucose and insulin on the transcriptome of cultured fibroblasts.
- Onelia Gagliano
- , Camilla Luni
- & Nicola Elvassore
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Article
| Open Access
NTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity
Calcitonin receptor-expressing neurons of the nucleus tractus solitarius contribute to long-term control of food intake and body weight. The authors show that a subset of these cells expresses Prlh and that enhancing Prlh-mediated neurotransmission from the NTS dampens hypothalamically-driven hyperphagia and obesity in mice.
- Wenwen Cheng
- , Ermelinda Ndoka
- & Martin G. Myers Jr
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Article
| Open Access
Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila
Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in neurofibromin and associated with disruptions in physiology and behavior. Here the authors show that neurofibromin regulates metabolic homeostasis via a discrete brain circuit in a Drosophila model of NF1.
- Valentina Botero
- , Bethany A. Stanhope
- & Seth M. Tomchik
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Article
| Open Access
Hexosamine biosynthetic pathway and O-GlcNAc-processing enzymes regulate daily rhythms in protein O-GlcNAcylation
Misalignment between lifestyle and the natural day-night cycle, such as mistimed eating, can negatively impact health. Here the authors show that mistimed feeding alters protein O-GlcNAcylation, a nutrient sensitive post-translational modification.
- Xianhui Liu
- , Ivana Blaženović
- & Joanna C. Chiu
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Article
| Open Access
A neuronal ensemble encoding adaptive choice during sensory conflict in Drosophila
The valence of information about food sources can be conflicting. Here, the authors show that activity in a small population of neurons projecting to the fan-shaped body of Drosophila represents food choice during sensory conflict.
- Preeti F. Sareen
- , Li Yan McCurdy
- & Michael N. Nitabach
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Article
| Open Access
The insulo-opercular cortex encodes food-specific content under controlled and naturalistic conditions
Animal studies have shown that insulo-opercular network function is critical in gustation and in behaviour based on anticipated food availability. The authors describe activities within the human insulo-opercular cortex which underlie anticipatory food evaluation in both controlled and naturalistic settings.
- Yuhao Huang
- , Bina W. Kakusa
- & Casey H. Halpern
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Article
| Open Access
Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue
During the expansion of adipose tissue adipocyte progenitor cells proliferate and undergo adipogenesis. Here, the authors show that adipocyte progenitor cell proliferation in visceral adipose tissue has a diurnal pattern, which is dependent on both energy intake and the circadian clock.
- Aleix Ribas-Latre
- , Rafael Bravo Santos
- & Kristin L. Eckel-Mahan
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Review Article
| Open Access
Importance of circadian timing for aging and longevity
Circadian clocks link physiologic processes to environmental conditions and a mismatch between internal and external rhythms has negative effects on organismal health. In this review, the authors discuss the interactions between circadian clocks and dietary interventions targeted to promote healthy aging.
- Victoria A. Acosta-Rodríguez
- , Filipa Rijo-Ferreira
- & Joseph S. Takahashi
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Article
| Open Access
Peripheral-specific Y1 receptor antagonism increases thermogenesis and protects against diet-induced obesity
Neuropeptide Y signalling in the periphery contributes to the regulation of metabolic and energy homeostasis. Here the authors show that blocking Y1R signalling in peripheral tissues using the selective antagonist BIBO3304 ameliorates diet-induced obesity and improves whole-body glucose metabolism.
- Chenxu Yan
- , Tianshu Zeng
- & Yan-Chuan Shi
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Article
| Open Access
Input-specific modulation of murine nucleus accumbens differentially regulates hedonic feeding
Hedonic feeding occurs in the absence of metabolic need and plays a critical role in the excessive feeding that underlies obesity. The authors show that optogenetic manipulation of NAc inputs from the prefrontal cortex versus inputs from the anterior paraventricular nucleus of the thalamus has opposite effects on high fat intake.
- Daniel J. Christoffel
- , Jessica J. Walsh
- & Robert C. Malenka
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Article
| Open Access
Lipocalin 2 mediates appetite suppression during pancreatic cancer cachexia
Lipocalin 2 (LCN2) has been recently identified as an endogenous regulator of appetite. Here, using pancreatic cancer as a model of cachexia, the authors demonstrate that LCN2 is a critical mediator of cancer-associated anorexia and may be therapeutically targeted to improve patient outcomes.
- Brennan Olson
- , Xinxia Zhu
- & Daniel L. Marks
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Article
| Open Access
Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways
Advances in wireless technologies have enabled internalisation of light sources, but organ specific illumination is challenging. Here, the authors present a durable, multimodal, wireless system enabling optogenetic stimulation of peripheral neurons within organs.
- Woo Seok Kim
- , Sungcheol Hong
- & Sung Il Park
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Article
| Open Access
An excitatory ventromedial hypothalamus to paraventricular thalamus circuit that suppresses food intake
The ventromedial hypothalamus (VMH) serves as a satiety center in the brain, however, the neural circuits involved are incompletely understood. Here, the authors decipher a neural circuit from VMH to the paraventricular thalamus that suppresses food intake.
- Jia Zhang
- , Dan Chen
- & Yunlei Yang
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Article
| Open Access
A ventrolateral medulla-midline thalamic circuit for hypoglycemic feeding
Catecholaminergic neurons of the ventrolateral medulla are known to drive diverse glucose counterregulatory responses to hypoglycemia. Here, the authors show that projections from these neurons onto nucleus accumbens-targeting neurons of the midline thalamus selectively mediate hypoglycemic feeding.
- B. Sofia Beas
- , Xinglong Gu
- & Mario A. Penzo
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Article
| Open Access
Feeding-dependent tentacle development in the sea anemone Nematostella vectensis
How the developmental capacity of long-lived animals copes with fluctuations in the food supply is unclear. Here, the authors show using the sea anemone Nematostella vectensis that the crosstalk between Target of Rapamycin and fibroblast growth factor signalling in ring muscles links postembryonic tentacle patterning with food availability.
- Aissam Ikmi
- , Petrus J. Steenbergen
- & Matthew C. Gibson
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Article
| Open Access
Circadian regulation of hedonic appetite in mice by clocks in dopaminergic neurons of the VTA
In addition to promoting overconsumption, palatable diets dampen daily intake patterns, which further augments metabolic dysfunction. Here, the authors find that in mice, circadian clocks in dopaminergic neurons in the ventral tegmental area drive hedonic appetite rhythms.
- C. E. Koch
- , K. Begemann
- & H. Oster
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Article
| Open Access
The endoplasmic reticulum stress-autophagy pathway controls hypothalamic development and energy balance regulation in leptin-deficient neonates
Overnutrition is associated with hypothalamic ER stress and impaired leptin signaling. Here the authors show that ER stress already occurs in neonates and that treatment with the ER stress relieving drug TUDCA early in life has beneficial metabolic and neurodevelopmental effects.
- Soyoung Park
- , Aleek Aintablian
- & Sebastien G. Bouret
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Article
| Open Access
TrkB-expressing paraventricular hypothalamic neurons suppress appetite through multiple neurocircuits
The TrkB receptor is known to regulate obesity via appetite control, but the underlying neural circuits are not known. Here, the authors show that selective modulation of TrkB+ neurons in the paraventricular hypothalamus regulates food intake via circuits to ventromedial hypothalamus and lateral parabrachial nucleus.
- Juan Ji An
- , Clint E. Kinney
- & Baoji Xu
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Article
| Open Access
The anterior insular cortex unilaterally controls feeding in response to aversive visceral stimuli in mice
Food intake can be attenuated by visceral aversive stimuli in pathological conditions. Here the authors identify a unilateral neural circuit from the CamKII-positive neurons in the anterior insular cortex to the vGluT2-positive neurons in the lateral hypothalamus that controls feeding responses to visceral aversive stimuli.
- Yu Wu
- , Changwan Chen
- & Shuang Qiu
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Article
| Open Access
NPY mediates the rapid feeding and glucose metabolism regulatory functions of AgRP neurons
AgRP-expressing neurons regulate feeding, glucose homeostasis and locomotor activity, but the neurotransmitters that mediate these effects are unclear. Here the authors show that neuropeptide Y in these neurons regulates rapid feeding responses and insulin sensitivity, but not locomotor activity.
- Linda Engström Ruud
- , Mafalda M. A. Pereira
- & Jens C. Brüning
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Article
| Open Access
DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice
AgRP neurons in the hypothalamic arcuate nucleus (ARH) are involved in regulating hunger and energy balance. Here the authors show that knockout of the DNA methyltransferase Dnmt3a in AgRP neurons of the ARH leads to a reduction in voluntary exercise along with numerous epigenetic and gene expression changes in ARH neurons.
- Harry MacKay
- , C. Anthony Scott
- & Robert A. Waterland
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Article
| Open Access
Hypothalamus-hippocampus circuitry regulates impulsivity via melanin-concentrating hormone
Impulsive behaviour is common in various neuropsychiatric disorders. Here, the authors identify a pathway from the lateral hypothalamus to the ventral hippocampus and the role of melanin-concentrating hormone signaling in these neurons in specifically regulating impulsivity.
- Emily E. Noble
- , Zhuo Wang
- & Scott E. Kanoski
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Article
| Open Access
The TLR7/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer
In the treatment of pancreatic ductal adenocarcinoma (PDAC), comorbidities such as cachexia limit quality of life and survival. Here, the authors show TLR7/8 agonist R848 remodels host and tumour immune responses, promoting survival and attenuating cachexia in murine models of PDAC.
- Katherine A. Michaelis
- , Mason A. Norgard
- & Daniel L. Marks
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Article
| Open Access
Hypothalamic neuronal circuits regulating hunger-induced taste modification
Hunger modulates perception of good and bad tastes. Here, the authors report that orexigenic AgRP neurons in the hypothalamus mediate these effects through glutamatergic lateral hypothalamic neurons that send distinct projections to the lateral septum and lateral habenula.
- Ou Fu
- , Yuu Iwai
- & Ken-ichiro Nakajima
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Article
| Open Access
Rapid metabolic shifts occur during the transition between hunger and satiety in Drosophila melanogaster
The relationship between metabolomic and behavioral changes is not well understood. Here, the authors analyze metabolome changes in D. melanogaster heads and bodies during hunger and satiety, and develop the Flyscape tool to visualize the resulting metabolic networks and integrate them with other omics data.
- Daniel Wilinski
- , Jasmine Winzeler
- & Monica Dus
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Article
| Open Access
A bed nucleus of stria terminalis microcircuit regulating inflammation-associated modulation of feeding
Inflammation can reduce food intake. Here the authors show that the GABAergic pathway from bed nucleus of stria terminalis to lateral hypothalamus regulates the inflammation induced reduction in feeding in mice.
- Yong Wang
- , JungMin Kim
- & Haijiang Cai
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Article
| Open Access
Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis
Neurons expressing pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here the authors show that Steroid Receptor Coactivator-1 (SRC-1) regulates the function of Pomc expressing neurons, and that rare heterozygous variants found in obese individuals lead to loss of SRC-1 function.
- Yongjie Yang
- , Agatha A. van der Klaauw
- & Yong Xu
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Article
| Open Access
Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons
Glucagon-like peptide 1 (GLP-1) is released from intestinal L-cells following nutrient uptake and enhances insulin release as well as promotes satiety. Here, the authors demonstrate that GLP-1 secreting cells release ATP and that this stimulates nodose neurons and enterocytes in a paracrine manner in vitro.
- Van B. Lu
- , Juraj Rievaj
- & Frank Reimann
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Article
| Open Access
Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons
Reduction in food intake elicits neuroendocrine adaptations to counterregulate the negative energy balance, e.g. via reduction in leptin levels. Here, the authors identify an additional starvation signal, growth hormone (GH). Blocking GH receptor attenuates the fall of whole body energy expenditure during food deprivation in mice.
- Isadora C. Furigo
- , Pryscila D. S. Teixeira
- & J. Donato Jr
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Article
| Open Access
Intestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis
Obesity is associated with altered N-acylethanolamine levels (NAE). Here the authors show that deletion of the gene encoding N-acylphosphatidylethanolamine phospholipase D, a key enzyme for NAE synthesis, in intestinal cells of mice leads to the development of obesity and hepatic steatosis via a mechanism involving the gut-brain axis.
- Amandine Everard
- , Hubert Plovier
- & Patrice D. Cani
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Article
| Open Access
Regulation of substrate utilization and adiposity by Agrp neurons
Agouti-related peptide (AgRP) producing neurons regulate food intake and metabolic processes in peripheral organs. Here, the authors show that hypothalamic AgRP neurons alter whole body substrate utilization to favour carbohydrate usage and lipid storage.
- João Paulo Cavalcanti-de-Albuquerque
- , Jeremy Bober
- & Marcelo O. Dietrich
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Article
| Open Access
Effective weight control via an implanted self-powered vagus nerve stimulation device
Developing new technologies for the neuromodulation of the vagus nerve can enable therapeutic strategies for body weight control in obese patients. Here, the authors present a battery-free self-powered implantable vagus nerve stimulation system that electrically responds to stomach movement.
- Guang Yao
- , Lei Kang
- & Xudong Wang
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Article
| Open Access
A phenotypic Caenorhabditis elegans screen identifies a selective suppressor of antipsychotic-induced hyperphagia
The molecular pathway(s) driving antipsychotics (AP) induced hyperphagia remains unclear. A novel C. elegans system is used here to screen for FDA approved drugs that selectively suppresses this response, unraveling potential molecular mediators influencing AP induced hyperphagia in mouse models.
- Anabel Perez-Gomez
- , Maria Carretero
- & Michael Petrascheck
A sex-specific thermogenic neurocircuit induced by predator smell recruiting cholecystokinin neurons in the dorsomedial hypothalamus