Nature<\/em><\/a>.<\/p>\nWorking with researchers from the UK, Japan, China, and the US, the Campinas team helped to identify and characterize the new role of NPY in experiments on laboratory animal cells. The first step was to identify and map which neurons of the sympathetic nervous system released the neurotransmitter. This part of the nervous system is activated in situations of stress or danger, and prepares the body for fight or flight. Some of these neurons also innervate the white fatty tissue, which specializes in storing energy in the form of fat; and the brown, which consumes fat and transforms it into heat.<\/p>\n
At the UK\u2019s University of Oxford, a group working under Portuguese neuroscientist Ana Domingos used antibodies that adhere to NPY to mark it and track its release in the fat tissue. The researchers found that some 40% of sympathetic system neurons arriving at the fat tissue produce the neurotransmitter, noting that they also connect to the mural cells, which envelop the small arteries (arterioles) but take blood laden with oxygen and nutrients to the fat tissue. Laboratory testing demonstrated that NPY induces proliferation of the neural cells, and their transformation into thermogenic adipocytes, which consume energy and release heat when the body is subjected to cold or physical activity; these cells are the key component of brown adipose tissue.<\/p>\n
\u201cOur work confirms that the NPY secreted by the peripheral nerve stimulates the formation of brown fat tissue,\u201d explains Domingos, coordinator of the study, to Pesquisa FAPESP<\/em>. This type of fat is rich in mitochondria, cell structures specialized in producing energy, but in a type that also generates heat. In early life, brown fat is present in large quantities in the human body, almost disappearing in adults and being replaced by a beige fat with fewer mitochondria. \u201cIt is estimated that these tissues expend 200 to 300 kilocalories per day, equivalent to around 10% of the total normally ingested by a person,\u201d Portuguese physiologist Jorge Ruas, of the University of Michigan, who did not participate in the study, told Pesquisa FAPESP<\/em>.<\/p>\nAt UNICAMP, Velloso\u2019s team tested the effects of an absence of NPY in the sympathetic nervous system. Mice genetically modified not to produce this neurotransmitter only in the peripheral nerves had a lower body temperature and expended some 10% less energy than those in the control group, who secreted the neuropeptide in the whole organism. With a normal diet, rodents from the first group became obese after adulthood, even when consuming the same amount of food as those in the second. \u201cThey expended less energy and stored part of it in the form of fat,\u201d says Velloso. When fed on a hypercaloric diet rich in fats, the animals not producing the neuropeptide put on more weight more quickly.<\/p>\n
The study\u2019s authors also observed that fat-rich diets damaged the NPY-producing neurons in the sympathetic nervous system, and led to the reduction of mural cells around the arterioles. As a consequence, the blood vessels became more permeable and allowed the overflow of liquid and passage of defense cells, causing inflammation in the fat tissue, a characteristic of obesity.<\/p>\n
Brazilian neuroscientist Ivan de Ara\u00fajo, director of the Max Planck Institute for Biological Cybernetics in Germany, who did not participate in the study, was most surprised by the NPY stimulating the differentiation of the mural cells in thermogenic adipocytes. \u201cFor the first time, the study shows that this neurotransmitter plays an important biological role in the sympathetic nervous system, and paves the way for the creation of new medications to modulate energy expenditure,\u201d he says.<\/p>\n
\u201cOur findings suggest that it would be possible to develop compounds that stimulate the basal metabolism and energy expenditure without affecting appetite,\u201d says Oxford\u2019s Domingos.<\/p>\n
Medications based on GLP-1 hormone analogs, such as semaglutide or tirzepatide, which have become well-known in the treatment of diabetes and obesity, act on the brain and reduce appetite, but do not stimulate energy expenditure. \u201cThe loss of fat with this type of treatment is limited, as the body compensates the reduced ingestion by lowering energy output,\u201d highlights Velloso. He says that a medication with similar effects to those of NPY would stimulate the formation of brown fat and energy use, prolonging weight loss caused by appetite reduction medicines.<\/p>\n
\u201cOne of the challenges,\u201d says Max Planck\u2019s Ara\u00fajo, \u201cis to find a way of activating only the mural cells, as in other parts of the body the NPY receptors can have different effects.\u201d Ruas, of Michigan, adds that it is necessary to confirm whether the increase in brown fat would in fact help a person to lose weight. \u201cThere could be an increase in body temperature and sweating, and it\u2019s important to check whether these effects will be tolerable,\u201d he says.<\/p>\n
The story above was published with the title “A dual-action neurotransmitter<\/strong>” in issue 345 of November\/2024.<\/p>\nScientific article
\n<\/strong>ZHU, Y. et al<\/em>. Sympathetic neuropeptide Y protects from obesity by sustaining thermogenic fat<\/a>. Nature<\/strong>. Aug. 28, 2024.<\/p>\n","protected":false},"excerpt":{"rendered":"Molecule known to act on the brain, stimulating appetite and weight gain, has the opposite effect when secreted by peripheral nerves, helping to burn fat","protected":false},"author":545,"featured_media":547983,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[159],"tags":[236],"coauthors":[1498],"class_list":["post-547982","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","tag-physiology"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/547982","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/545"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=547982"}],"version-history":[{"count":1,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/547982\/revisions"}],"predecessor-version":[{"id":547991,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/547982\/revisions\/547991"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media\/547983"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=547982"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=547982"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=547982"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=547982"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}