Neuropeptide Exocytosis Involving Synaptotagmin-4 and Oxytocin in Hypothalamic Programming of Body Weight and Energy Balance

Zhang, Guo; Bai, Hua; Zhang, Hai; Dean, Camin; Wu, Qiang; Li, Juxue; Guariglia, Sara R.; Meng, Qing‐Yuan; Cai, Dongsheng

doi:10.1016/j.neuron.2010.12.036

Cited by 183 publications

(280 citation statements)

References 67 publications

Supporting

Mentioning

259

Contrasting

Unclassified

Order By: Relevance

“…It is already well established that the hypothalamus is the regulatory center for feeding and satiety [26]. Oxytocin has also been linked to energy homeostasis mechanisms in animals, where it acts as a strong inhibitor of food intake and affects energy expenditure and glucose homeostasis [27][28][29][30][31]. Oxytocin has also been shown to play an important role in metabolism and energy balance in humans [32,33], such as reducing caloric intake with a preferential effect on fat intake [11] and reward-driven food intake in humans [34].…”

Section: Discussionmentioning

confidence: 99%

Oxytocin in survivors of childhood-onset craniopharyngioma

et al. 2016

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Oxytocin in survivors of childhood-onset craniopharyngioma

et al. 2016

View full text Add to dashboard Cite

“…In addition, according to the transcriptomic assay, other regulators of dynamic cell interactions and synaptogenesis might also be involved in diet-induced hypothalamic plasticity. Indeed, syndecan-3 and synaptotagmin-4 are promising targets to control obesity and related diseases (Strader et al, 2004;Zhang et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

et al. 2012

View full text Add to dashboard Cite

Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opiomelanocortin (POMC) neurons. We identified the polysialic acid molecule (PSA) as a mediator of the diet-induced rewiring of arcuate POMC. Moreover, local pharmacological inhibition and genetic disruption of the PSA signaling limits the behavioral and metabolic adaptation to HFD, as treated mice failed to normalize energy intake and showed increased body weight gain after the HFD challenge. Altogether, these findings reveal the existence of physiological hypothalamic rewiring involved in the homeostatic response to dietary fat. Furthermore, defects in the hypothalamic plasticitydriven adaptive response to HFD are obesogenic and could be involved in the development of metabolic diseases.

show abstract

“…Importantly, oxytocin has also been convincingly linked with protection from obesity [17][18][19][20][21][22][23]. While the nonapeptide oxytocin is historically recognized for its role in parturition [24] and lactation [25] it has gained more recent attention for its apparent effects on prosocial behavior [26,27] and therapeutic potential in the treatment of autism spectrum disorder (ASD) [26,27], schizophrenia [26,28] and obesity [17][18][19][20][21][22][23]. A large number of ongoing investigations in humans list oxytocin as the focus in studies on caloric intake, gastric emptying, or obesity, as displayed in the ClinicalTrials.…”

Section: Introductionmentioning

confidence: 99%

“…gov registry, National Institutes of Health. Specifically, studies show oxytocin has roles in reducing food intake and body weight in dietinduced obesity [17,19,[21][22][23] in genetically obese rodent models [18,20,21], highlighting potential downstream CNS and peripheral mechanisms. It was also shown that intranasal administration of oxytocin in humans lowers caloric intake and has beneficial metabolic effects, resulting in a shift from carbohydrate to fat utilization and improved insulin sensitivity [29].…”

Section: Introductionmentioning

confidence: 99%

Beneficial Dog Bacteria Up-Regulate Oxytocin and Lower Risk of Obesity

Varian¹,

Levkovich²,

Poutahidis³

et al. 2017

J Prob Health

View full text Add to dashboard Cite

AnimalsC57BL/6 wild type (wt), oxytocin-wt (oxt-wt) and oxytocin- AbstractCohabitation with pet dogs imparts diverse health benefits to humans including a slim physique. It is known that neuropeptide hormone oxytocin fundamental in human-canine social bonds regulates appetite and body weight. It was recently shown in mice that consuming Lactobacillus reuteri ATCC 6475 from human breast milk lowers body weight and up-regulates oxytocin levels in blood. Here we test the hypothesis that bacteria from dog saliva may similarly modulate recipient host body weight. We find that a Lactobacillus spp isolate from dog saliva led to lower body weight when fed to C57BL/6 wild type mice. Mice consuming the canineborne L. reuteri also had elevated oxytocin levels in blood plasma, and exhibited body weight in an oxytocin-dependent manner. Interestingly, killed (lysed) canine bacteria were sufficient to achieve the physiological effects. Taken together, these studies provide evidence that dog bacteria modulate oxytocin levels and body weight in recipient mice, and thus may help reduce risk of obesity in individuals cohabitating with pet dogs. knockout (oxt-ko) B6; 129S-Oxttm1Wsy/J mice (purchased initially from Jackson labs; Bar Harbor, ME) were used in three separate experiments (Figure 1). Mice were housed and handled in Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)-accredited facilities using techniques and diets including Lactobacillus reuteri as specifically approved by Massachusetts Institute of Technology's (MIT) Committee on Animal Care (CAC). Mice were housed under standard 12:12 light cycle conditions with lights on at 7 AM. Mice were fed a standard control chow Purina RMH3000. Beneficial Dog Bacteria Up-Regulate Oxytocin and Lower Risk of ObesityMice were bred in-house to achieve experimental groups. Each experiment included 5-15 animals per group with one or two replications (total N=10-30 mice examined per group) unless otherwise specified. For the initial studies, C57BL/6 wt mice received Lactobacillus reuteri 2546 isolated from dog saliva. To test putative roles for microbeinduced oxytocin in obesity, oxt-ko mice and their oxt-wt littermates entered experiments at eight weeks of age. At the conclusion of the study mice were euthanized with CO 2 overdose, and were examined as described below. Eight pet dogs served as saliva microbe donors as approved by the MIT-CAC. Saliva was collected from these dogs in the morning before feeding using sterile swabs [Puritan Sterile Polyester Tipped applicators Guilford, Me Ref: 25-806 1PD] in 1.5 ml centrifuge tubes (Safeseal Microcentrifuge Tubes, Sorenson Bioscience Inc. Salt Lace City, UT Cat# 16070). Bacteria were purified from dog saliva as described in detail below. PCR of dog saliva for all Lactobacillus speciesSaliva was collected from eight pet dogs and prepared using High Pure PCR Template kit (Roche Diagnostics) was used without changes to the manufacturer's directions to isolate DNA from the canine saliva. DNA was measured using Nan...

show abstract

Neuropeptide Exocytosis Involving Synaptotagmin-4 and Oxytocin in Hypothalamic Programming of Body Weight and Energy Balance

Cited by 183 publications

References 67 publications

Oxytocin in survivors of childhood-onset craniopharyngioma

Oxytocin in survivors of childhood-onset craniopharyngioma

Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

Beneficial Dog Bacteria Up-Regulate Oxytocin and Lower Risk of Obesity

Contact Info

Product

Resources

About