Blunted Vagal Cocaine- and Amphetamine-Regulated Transcript Promotes Hyperphagia and Weight Gain

Lee, Shin J.; Krieger, Jean‐Philippe; Vergara, Macarena; Quinn, Danielle; McDougle, Molly; Araujo, Alan de; Darling, Rebecca A.; Zollinger, Benjamin; Anderson, Seth; Pan, Annabelle; Simonnet, Emilie J.; Pignalosa, Angelica; Arnold, Myrtha; Singh, Avninder; Langhans, Wolfgang; Raybould, Helen E.; Lartigue, Guillaume de

doi:10.1016/j.celrep.2020.01.045

Cited by 28 publications

(25 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The meal patterns changes in rats were restricted to the dark phase irrespective of diet, presumably because rodents consume the majority of their food in the dark. Interestingly, other feeding studies in which vagal sensory signalling was impaired also reported disruption of meal patterns only in the dark, 49,50,70 and is therefore a conserved phenomenon. In HFHS‐fed animals, vagal gut‐brain signalling conveys signals that affect both satiation and satiety, resulting in pronounced hyperphagia.…”

Section: Discussionmentioning

confidence: 95%

“…Furthermore, post‐prandial neuronal activation in the NTS is significantly lower in obese, compared to lean, rats, 47,91 suggesting that gut‐brain signalling is severely blunted. Our previous work demonstrates that disrupted vagal signalling coincides with the onset of hyperphagia 44,50 . The exact mechanism by which vagal signalling is reduced in obesity remains unclear but may involve blunted receptor expression, 44,92‐95 impaired neuropeptide release 50 and/or altered biophysical properties 37 .…”

Section: Discussionmentioning

confidence: 97%

“…In rats, reduced vagal sensing coincides with the onset of hyperphagia and is associated with increased body weight 48 . In a genetic mouse study, inhibition of vagal signalling resulted in a reduction of vagal afferent sensitivity to CCK and was sufficient to induce hyperphagia and weight gain 49,50 . Conversely, chronic vagal stimulation reduces food intake and body weight in many different animal species, 51‐56 including humans 57 .…”

Section: Introductionmentioning

confidence: 99%

“…Subdiaphragmatic vagal deafferentation approach improves on vagotomy and capsaicin by leaving 50% of motor control intact, but similarly lacks organ specificity 68 . While more targeted viral‐mediated RNA interference approaches have been employed, 50,69,70 this requires a priori knowledge of the signalling receptor to be knocked down. To address these issues, we have recently validated a novel pharmacotoxin approach, in which the neurotoxin saporin (SAP) is conjugated to the gastrointestinal hormone CCK (CCK‐SAP), for selectively deleting CCK receptor‐expressing sensory vagal neurones that innervate the stomach and small intestine 71 .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Intact vagal gut‐brain signalling prevents hyperphagia and excessive weight gain in response to high‐fat high‐sugar diet

et al. 2020

Self Cite

View full text Add to dashboard Cite

Aim The tools that have been used to assess the function of the vagus nerve lack specificity. This could explain discrepancies about the role of vagal gut‐brain signalling in long‐term control of energy balance. Here we use a validated approach to selectively ablate sensory vagal neurones that innervate the gut to determine the role of vagal gut‐brain signalling in the control of food intake, energy expenditure and glucose homoeostasis in response to different diets. Methods Rat nodose ganglia were injected bilaterally with either the neurotoxin saporin conjugated to the gastrointestinal hormone cholecystokinin (CCK), or unconjugated saporin as a control. Food intake, body weight, glucose tolerance and energy expenditure were measured in both groups in response to chow or high‐fat high‐sugar (HFHS) diet. Willingness to work for fat or sugar was assessed by progressive ratio for orally administered solutions, while post‐ingestive feedback was tested by measuring food intake after an isocaloric lipid or sucrose pre‐load. Results Vagal deafferentation of the gut increases meal number in lean chow‐fed rats. Switching to a HFHS diet exacerbates overeating and body weight gain. The breakpoint for sugar or fat solution did not differ between groups, suggesting that increased palatability may not drive HFHS‐induced hyperphagia. Instead, decreased satiation in response to intra‐gastric infusion of fat, but not sugar, promotes hyperphagia in CCK‐Saporin‐treated rats fed with HFHS diet. Conclusions We conclude that intact sensory vagal neurones prevent hyperphagia and exacerbation of weight gain in response to a HFHS diet by promoting lipid‐mediated satiation.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intact vagal gut‐brain signalling prevents hyperphagia and excessive weight gain in response to high‐fat high‐sugar diet

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The anorectic effect of CCK is impaired in HFD-fed mice and rats 55 , as is vagal afferent activation 55 , although this has not been fully examined in humans. Further, CCK-1R expression in vagal nerves is decreased in HFD induced obese rats 56 , ultimately contributing to reduced nodose ganglia cocaine and amphetamine-regulated transcript (CART) expression, a neuropeptide regulating energy homeostasis, in association with increased food intake and body weight 64 . However, vagal CCK resistance during obesity could also be due to obesity-associated leptin resistance, as the leptin receptor is co-expressed with CCK-1R in the vagal afferent neurons 65 and leptin potentiates the suppressive effect of CCK on appetite and increases vagal afferent activation following CCK administration 66 , 67 .…”

Section: Gi Nutrient-sensing Physiologymentioning

confidence: 99%

The metabolic impact of small intestinal nutrient sensing

et al. 2021

View full text Add to dashboard Cite

The gastrointestinal tract maintains energy and glucose homeostasis, in part through nutrient-sensing and subsequent signaling to the brain and other tissues. In this review, we highlight the role of small intestinal nutrient-sensing in metabolic homeostasis, and link high-fat feeding, obesity, and diabetes with perturbations in these gut-brain signaling pathways. We identify how lipids, carbohydrates, and proteins, initiate gut peptide release from the enteroendocrine cells through small intestinal sensing pathways, and how these peptides regulate food intake, glucose tolerance, and hepatic glucose production. Lastly, we highlight how the gut microbiota impact small intestinal nutrient-sensing in normal physiology, and in disease, pharmacological and surgical settings. Emerging evidence indicates that the molecular mechanisms of small intestinal nutrient sensing in metabolic homeostasis have physiological and pathological impact as well as therapeutic potential in obesity and diabetes.

show abstract

Connectivity and molecular profiles of Foxp2‐ and Dbx1‐lineage neurons in the accessory olfactory bulb and medial amygdala

Prakash,

Matos,

Sebaoui

et al. 2023

J of Comparative Neurology

View full text Add to dashboard Cite

In terrestrial vertebrates, the olfactory system is divided into main (MOS) and accessory (AOS) components that process both volatile and nonvolatile cues to generate appropriate behavioral responses. While much is known regarding the molecular diversity of neurons that comprise the MOS, less is known about the AOS. Here, focusing on the vomeronasal organ (VNO), the accessory olfactory bulb (AOB), and the medial amygdala (MeA), we reveal that populations of neurons in the AOS can be molecularly subdivided based on their ongoing or prior expression of the transcription factors Foxp2 or Dbx1, which delineate separate populations of GABAergic output neurons in the MeA. We show that a majority of AOB neurons that project directly to the MeA are of the Foxp2 lineage. Using single‐neuron patch‐clamp electrophysiology, we further reveal that in addition to sex‐specific differences across lineage, the frequency of excitatory input to MeA Dbx1‐ and Foxp2‐lineage neurons differs between sexes. Together, this work uncovers a novel molecular diversity of AOS neurons, and lineage and sex differences in patterns of connectivity.

show abstract

Blunted Vagal Cocaine- and Amphetamine-Regulated Transcript Promotes Hyperphagia and Weight Gain

Cited by 28 publications

References 60 publications

Intact vagal gut‐brain signalling prevents hyperphagia and excessive weight gain in response to high‐fat high‐sugar diet

Intact vagal gut‐brain signalling prevents hyperphagia and excessive weight gain in response to high‐fat high‐sugar diet

The metabolic impact of small intestinal nutrient sensing

Connectivity and molecular profiles of Foxp2‐ and Dbx1‐lineage neurons in the accessory olfactory bulb and medial amygdala

Contact Info

Product

Resources

About