Peripheral oxytocin treatment ameliorates obesity by reducing food intake and visceral fat mass

Maejima, Yuko; Iwasaki, Yusaku; Yamahara, Yui; Kodaira, Misato; Sedbazar, Udval; Yada, Toshihiko

doi:10.18632/aging.100408

Cited by 191 publications

(321 citation statements)

References 25 publications

(31 reference statements)

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“…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

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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...

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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

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“…Various strategies have been proposed to treat obesity by promoting fat mobilization, increasing energy expenditure, and/or reducing food intake [1,7]. Accumulating evidence has shown that diets with higher protein and reduced carbohydrates are beneficial for weight loss and increase loss of body fat [8][9][10].…”

Section: Amino Acids and Obesitymentioning

confidence: 99%

Branched chain amino acids and metabolic regulation

Wang

Guo

2013

Chin. Sci. Bull.

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Amino acids are fundamental nutrients required for protein synthesis. The branched chain amino acids (BCAAs) leucine, isoleucine, and valine are the most abundant of the essential amino acids. BCAAs have recently been recognized as having functions in processes other than simple nutrition. For example, metabolic diseases are characterized by higher levels of circulating BCAAs. Moreover, supplementation with or deficiency in BCAAs is closely related to the regulation of metabolic homeostasis. Indeed, leucine deprivation induces increased lipolysis and thermogenesis, which result in fat loss, as well as suppressed lipogenesis and enhanced insulin sensitivity in the liver. Accumulating evidence has indicated that several amino acid sensors, including GCN2, ATF4, mTOR, and AMPK, play pivotal roles in the regulation of lipid metabolism, glucose metabolism, and energy homeostasis. Furthermore, the hypothalamus is critical for sensing amino acid levels and mediates the metabolic adaptation of the body upon limitation of essential amino acids (EAAs) through regulating expression of the S6K1, MC4R, and CRH. In this review, we highlight recent studies investigating the cellular mechanisms linking amino acids, amino acid sensors, metabolic regulation, and metabolic diseases. Amino acid sensing and metabolic regulation have become research hotspots in the metabolic field.branched chain amino acids, amino acid sensor, lipid metabolism, glucose metabolism, energy homeostasis, obesity, diabetes Citation:Wang C X, Guo F F. Branched chain amino acids and metabolic regulation.

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“…Animals developed obesity when they were deficient of OT or OT receptors [15] [16]. Peripheral OT treatment reduced adipose tissue proportion and also ameliorated food intake, fatty liver, as well as glucose intolerance in ob/ob mice [17] [18] [19]. Adipocyte size was smaller after treating with OT, the lipogenic related genes fatty acid binding protein 4 (FABP4), peroxisomal proliferator activated receptor gamma (PPARγ), glucose transporter 4 (GLUT4), and leptin mRNA levels in adipose tissues were increased in rats, indicating that OT treatment improves nutrient provision in adipose tissue [20].…”

mentioning

confidence: 99%

“…Glucagon and insulin were released by OT stimulations in isolated pancreas and islets of rodents [23] [24]. Daily peripheral injection and infusion of OT improved glucose tolerance test in mice with high-fat diet feeding [17] [25]. OT increased glucose uptake of cardiomyocytes through AKT/PKB phosphorylation in rodent [8] [26].…”

mentioning

confidence: 99%

Modulation of Fatty Acid Oxidation and Glucose Uptake by Oxytocin in Adipocytes

Lin¹,

Chen²,

Chen³

et al. 2017

JBiSE

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Oxytocin (OT) is a hypothalamic neuropeptide synthesized and secreted by OT neurons. In addition to its conventional role in reproductive physiology, central OT also regulates various social behaviors, such as care, trust, and emotions. Central and subcutaneous OT infusions stimulate lipid metabolism in mice and rats when fed standard or high fat diets. Mice lacking the OT receptor (OTR) or OT peptide develop late-onset obesity with greater fat pad weights, larger adipocyte size and elevated plasma levels of leptin. To study the effects of OT on lipid metabolism, we examined the effects of serial OT doses (0, 10, 30, 100, 150, 300 nM) on 3T3L1 adipocytes, together with long (144 hours, 6 days) and short (24 hours, 1 day) term treatments. The shortterm treatment with 150 nM OT increased triacylglycerol (TAG) accumulation and decreased mRNA expressions of carnitine palmitoyltransferase 1α (CPT-1α) and fatty acid binding protein 4 (FABP4). After long-term incubation with 150 nM OT, only the CPT-1α mRNA was decreased. In differentiated adipocytes derived from pig adipose tissue stem cells, only hormone sensitive lipase mRNA was decreased after short-or long-term treatment with OT. To obtain further insight into the underlying mechanism of OT induction, we tested the involvement of the AKT/PKB pathway; however, AKT phosphorylation was decreased after treatment with 150 nM OT, suggesting that OT effects may be independent from the AKT/PKB pathway. Taken together, OT effects on adipocyte glucose and lipid metabolism are probably through mechanisms other than the AKT/PKB pathway.

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Peripheral oxytocin treatment ameliorates obesity by reducing food intake and visceral fat mass

Cited by 191 publications

References 25 publications

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

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

Branched chain amino acids and metabolic regulation

Modulation of Fatty Acid Oxidation and Glucose Uptake by Oxytocin in Adipocytes

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