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Do appetite suppressants really work?Appetite control technology -
Food and Drug Administration-approved drug liraglutide has been shown to help obese patients lose weight by suppressing their appetite. However, where and how the drug acts in the brain was not fully understood, until now.
Filling this gap meets a need that has become a priority for researchers looking for new treatments to help fight the increasing rates of obesity. Liraglutide interacts with targets called glucagon-like peptide-1 receptors GLP-1R in various parts of the brain to suppress hunger.
This is the first study to show how a distinct group of neurons that express GLP-1Rs within the NTS of the brainstem play a key role in mediating these effects.
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Human genetics shape the gut microbiome. Download references. The authors would like to acknowledge and thank Nadia Everaert and Yong Zhao for their help editing this manuscript. The authors acknowledge the financial support from the National Natural Science Foundation , , Agricultural Science and Technology Innovation Program CAAS-ZDRW, ASTIP-IAS07 , and Central Public-interest Scientific Institution Basal Research Fund YGH in China.
State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, , China. Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, University of Liège, Passage de Déportés 2, , Gembloux, Belgium.
College of Animal Science and Technology, Hunan Agricultural University, Changsha, , China. Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, , China.
You can also search for this author in PubMed Google Scholar. HH and BY wrote the first draft of the manuscript. RQZ, SFZ, JM, NE, and JY helped to review the first draft of the manuscript. YLY, YZ, JY, LC, and HFZ reviewed and edited the final manuscript. The authors read and approved the final manuscript.
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Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Review Open access Published: 20 July From gut microbiota to host appetite: gut microbiota-derived metabolites as key regulators Hui Han ORCID: orcid.
Abstract Feelings of hunger and satiety are the key determinants for maintaining the life of humans and animals. Video abstract. Introduction Feelings of hunger and satiety are principal involuntary motivations for feeding behavior in humans and animals [ 1 , 2 , 3 , 4 ].
Full size image. Gut microbiota and appetite-related hormones The physiological control of appetite is mediated by circulating orexigenic and anorexigenic hormones e.
Ghrelin Contrary to leptin, ghrelin is mainly a stomach-derived hunger hormone that acts as a ligand for the growth hormone secretagogue receptor GSHR.
Insulin In addition to controlling glucose and energy homeostasis, insulin can function as a satiety signal [ 61 ]. Gut microbial metabolites and appetite It has long been suggested that gut microbial metabolites play a key role in generating energy and mediating microbiota-gut-brain communication, which may affect the physiological and psychological functions of mammals [ 68 , 69 ].
SCFAs The SCFAs i. Tryptophan Trp The gut microbiota plays an important role in controlling the availability and metabolism of Trp, which directly or indirectly regulates metabolic homeostasis and even appetite [ , , , ].
GABA GABA is a microbial metabolite from dietary glutamate and acts as a neurotransmitter that contributes to the communication between the gastrointestinal tract and brain [ ].
BCAAs BCAAs, including leucine, isoleucine, and valine, are derived from the diet as well as can be de novo by the gut microbiota. BAs BAs are synthesized in the liver and released into the gastrointestinal tract and are involved in intestinal absorption of lipid, as well as metabolic and inflammatory signaling pathways [ ].
Gut bacterial proteins The gut microbiota, including the bacteria, fungi, virus, and archaea, can produce identical protein sequences with appetite-regulating peptides i.
Clinical relevance Abnormal regulation of appetite can cause eating disorders and obesity [ , , ], which are severe and life-threating mental illness. Conclusions In this review, the direct and indirect molecular mechanisms how the gut microbiota regulates host appetite were summarized.
Availability of data and materials Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Abbreviations AN: Anorexia nervosa BN: Bulimia nervosa SCFAs: Short-chain fatty acids GRP Free fatty acid receptor 2 GRP Free fatty acid receptor 3 GLP Glucagon-like peptide PYY: peptide YY POMC: Pro-opiomelanocortin MSH: Melanocyte-stimulating hormone MC4R: Melanocortin-4 receptor GABA: γ-aminobutyric acid AgRP: Agouti-related peptide ARC: Arcuate nucleus Trp: Tryptophan 5-HT: Serotonin, 5-hydroxytryptamine NPY: Neuropeptide Y GH-IGF: Growth hormone-insulin-like growth factor CCK: Cholecystokinin BAs: Bile acids GF: Germ-free FXR: Farnesoid X receptor TGR5: Takeda G-protein-coupled bile acid receptor CART: Amphetamine-regulated transcript WT: Wild-type Angpt Angiopoietin-like protein 14 ClpB: Caseinolytic protease TLRs: Toll-like receptors PAMPs: Pathogen-associated molecular patterns LPS: Lipopolysaccharide Igs: Immunoglobulins mTORC1: Mtormechanistic target of rapamycin complex 1 ABA: Activity-based anorexia.
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MIT engineers have now come up with a new way to take advantage of that phenomenon, using an ingestible capsule that vibrates within the stomach. These vibrations activate the same stretch receptors that sense when the stomach is distended, creating an illusory sense of fullness.
Scientists have much more to learn about the mechanisms that influence human body weight, but if further research suggests this technology could be safely used in humans, such a pill might offer a minimally invasive way to treat obesity, the researchers say.
Srinivasan is the lead author of the new study, which appears today in Science Advances. When the stomach becomes distended, specialized cells called mechanoreceptors sense that stretching and send signals to the brain via the vagus nerve.
As a result, the brain stimulates production of insulin, as well as hormones such as C-peptide, Pyy, and GLP All of these hormones work together to help people digest their food, feel full, and stop eating.
At the same time, levels of ghrelin, a hunger-promoting hormone, go down. While a graduate student at MIT, Srinivasan became interested in the idea of controlling this process by artificially stretching the mechanoreceptors that line the stomach, through vibration. Previous research had shown that vibration applied to a muscle can induce a sense that the muscle has stretched farther than it actually has.
For this study, Srinivasan, Traverso, and a team of researchers designed a capsule about the size of a multivitamin, that includes a vibrating element. When the pill, which is powered by a small silver oxide battery, reaches the stomach, acidic gastric fluids dissolve a gelatinous membrane that covers the capsule, completing the electronic circuit that activates the vibrating motor.
In a study in animals, the researchers showed that once the pill begins vibrating, it activates mechanoreceptors, which send signals to the brain through stimulation of the vagus nerve. The researchers tracked hormone levels during the periods when the device was vibrating and found that they mirrored the hormone release patterns seen following a meal, even when the animals had fasted.
They found that when the pill was activated for about 20 minutes, before the animals were offered food, they consumed 40 percent less, on average, than they did when the pill was not activated.
The animals also gained weight more slowly during periods when they were treated with the vibrating pill. The current version of the pill is designed to vibrate for about 30 minutes after arriving in the stomach, but the researchers plan to explore the possibility of adapting it to remain in the stomach for longer periods of time, where it could be turned on and off wirelessly as needed.
In the animal studies, the pills passed through the digestive tract within four or five days. The study also found that the animals did not show any signs of obstruction, perforation, or other negative impacts while the pill was in their digestive tract.
This type of pill could offer an alternative to the current approaches to treating obesity, the researchers say.
These include gastric bypass surgery, as well as gastric balloons, which are no longer used widely in the United States due to safety concerns.
Drugs such as GLP-1 agonists can also aid weight loss, but most of them have to be injected, and they are unaffordable for many people. The researchers now plan to explore ways to scale up the manufacturing of the capsules, which could enable clinical trials in humans.
Other authors of the paper include Amro Alshareef, Alexandria Hwang, Ceara Byrne, Johannes Kuosmann, Keiko Ishida, Joshua Jenkins, Sabrina Liu, Wiam Abdalla Mohammed Madani, Alison Hayward, and Niora Fabian.
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