Oxytocin Deficiency Mediates Hyperphagic Obesity of Sim1 Haploinsufficient Mice

Kublaoui, Bassil; Gemelli, Terry; Tolson, Kristen P.; Wang, Yu; Zinn, Andrew R.

doi:10.1210/me.2008-0067

Cited by 213 publications

(244 citation statements)

References 58 publications

Supporting

Mentioning

231

Contrasting

Unclassified

Order By: Relevance

“…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%

See 1 more Smart Citation

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

Section: Introductionmentioning

confidence: 99%

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

show abstract

“…It has so far been studied mainly with a focus on hyperphagia and obesity, with an effect demonstrated by mice haploinsufficient for the SIM1 gene (Xi et al, 2012). It has been shown that SIM1 is important for oxytocin expression in the PVN, with a near 80% reduction in haploinsufficient mice (Kublaoui et al, 2008). In the PVN and SON, SIM1 is co-expressed with the transcription factor aryl hydrocarbon receptor nuclear translocator 2 (ARNT2).…”

Section: Introductionmentioning

confidence: 99%

Associations between oxytocin-related genes and autistic-like traits

Hovey

Zettergren

Jönsson

et al. 2014

Social Neuroscience

View full text Add to dashboard Cite

Oxytocin has repeatedly been shown to influence human behavior in social contexts; also, a relationship between oxytocin and the pathophysiology of Autism Spectrum Disorder (ASD) has been suggested. In the present study, we investigated SNPs in the oxytocin gene (OXT), and the genes for single-minded 1 (SIM1), aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), and cluster of differentiation 38 (CD38), in a population of 1771 children from the Child and Adolescent Twin Study in Sweden. Statistical analyses were performed to investigate any association between SNPs and autistic-like traits (ALTs), measured through ASD scores in the Autism-Tics, ADHD and other Comorbidities inventory. Our main finding was a statistically significant association between the SIM1 SNP rs3734354 (Pro352Thr) and ASD scores for language impairment (p=0.0004). Furthermore, nominal associations were found between ASD scores and SNPs in OXT, ARNT2 and CD38. In summary, the present study lends support to the hypothesis that oxytocin and oxytocin neuron development may have an influence on the development of ALTs, and suggests a new candidate gene in the search for the pathophysiology of ASD.

show abstract

“…Since then, many studies have linked changes in brain oxytocin signaling with changes in eating behavior: (1) hypothalamic oxytocin mRNA expression is reduced with fasting and is restored upon refeeding; (2) eating activated oxytocin neurons in rats; and (3) reduction of oxytocin mRNA and protein in the paraventricular nucleus led mice to develop obesity, which can be rescued by oxytocin treatment [345,346].…”

Section: Oxytocinmentioning

confidence: 99%

“…More recently, Blevins and colleagues [385,386] confirmed this and also showed that reductions in hindbrain oxytocin signaling reduce the satiating potency of CCK in rats. Leptin also seems to affect this oxytocin signaling: (1) leptin activated paraventricular nucleus oxytocin neurons and increased the expression of oxytocin mRNA in the paraventricular nucleus, probably via melanocortin-dependent mechanisms [345,350,387,388] and (2) third ventricular administration of oxytocin antagonists blunted leptin's anorectic effects and abolished its ability to enhance CCK activation of the NTS [350] as well as reversing the anorectic effect of α-MSH [389].…”

Section: Descending Projections For Satiationmentioning

confidence: 99%

Neuroendocrine control of satiation

Asarian¹,

Bächler

2014

Hormone Molecular Biology and Clinical Investigation

View full text Add to dashboard Cite

Abstract:Eating is a simple behavior with complex functions. The unconscious neuroendocrine process that stops eating and brings a meal to its end is called satiation. Energy homeostasis is mediated accomplished through the control of meal size via satiation. It involves neural integrations of phasic negative-feedback signals related to ingested food and tonic signals, such as those related to adipose tissue mass. Energy homeostasis is accomplished through adjustments in meal size brought about by changes in these satiation signals. The best understood meal-derived satiation signals arise from gastrointestinal nutrient sensing. Gastrointestinal hormones secreted during the meal, including cholecystokinin, glucagon-like peptide 1, and PYY, mediate most of these. Other physiological signals arise from activation of metabolic-sensing neurons, mainly in the hypothalamus and caudal brainstem. We review both classes of satiation signal and their integration in the brain, including their processing by melanocortin, neuropeptide Y/agouti-related peptide, serotonin, noradrenaline, and oxytocin neurons. Our review is not comprehensive; rather, we discuss only what we consider the best-understood mechanisms of satiation, with a special focus on normally operating physiological mechanisms.

show abstract

Oxytocin Deficiency Mediates Hyperphagic Obesity of Sim1 Haploinsufficient Mice

Cited by 213 publications

References 58 publications

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

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

Associations between oxytocin-related genes and autistic-like traits

Neuroendocrine control of satiation

Contact Info

Product

Resources

About