{"id":3145,"date":"2026-11-14T22:17:35","date_gmt":"2026-11-15T03:17:35","guid":{"rendered":"https:\/\/haidut.me\/?p=3145"},"modified":"2026-11-14T22:22:22","modified_gmt":"2026-11-15T03:22:22","slug":"by-lowering-dopamine-serotonin-5-ht-reduces-metabolism-physical-activity-endurance-promotes-fat-gain-oxidation","status":"publish","type":"post","link":"https:\/\/haidut.me\/?p=3145","title":{"rendered":"By lowering dopamine, serotonin (5-HT) reduces metabolism, physical activity, endurance; promotes fat gain\/oxidation"},"content":{"rendered":"

One of the rare studies that truly shines the light on just how systemically nefarious 5-HT is. It is well-known that in aging and chronic disease, there is a decrease in physical activity and motivation, as well as increase in fat mass, often combined with loss of muscle mass (sarcopenic obesity). Of course, mainstream medicine claims those are “multifactorial” processes that cannot really be ascribed to any single factor, but we are always assured that genes play a major role. Well, according to study below this “multifactorial” mystery is actually rather simple and it all comes down to metabolism. A post I did on mental illness about a year ago described 5-HT as the master metabolic regulator inside the brain, and stated that 5-HT is the main inhibitor of oxidative metabolism in the brain (and peripherally as well). Ergo, elevated 5-HT is expected to cause reduced energy production, translating to reduced physical activity and motivation, as well as increased weight gain in the form of fat, which is exactly what the study below discovered. The really damning part of the study is that it demonstrated that one of the most widely used “antidepressant” drugs of the SSRI class was able to cause all of those issues mentioned above. As such,\u00a0 it should be quite clear (as also hinted by the mental illness post mentioned above) to any reader that 5-HT is not at all an “antidepressant”, but more of a chemical “lobotomy” agent. It simply reduces the ability of the brain to respond to any stimulant\/event\/information, positive or negative, by reducing energy production and thus the ability to react to the external event. But back to the study – another great finding of the study was that blocking the 5-HT2C receptor was enough to reverse the negative effects of increased serotonin by the SSRI drug. The study authors opine that the effects of 5-HT are mediated through its ability to inhibit\/block dopamine release, considering that dopamine is a known promoter of oxidative metabolism, physical activity and fat loss.<\/p>\n

https:\/\/doi.org\/10.1016\/j.metabol.2026.156823<\/a><\/p>\n

https:\/\/lifespan.io\/serotonin-signals-suppress-physical-activity-in-aging-mice\/<\/a><\/p>\n

“…First, the researchers compared younger and older humans. Scottish volunteers aged 17-30 or 50-70 wore hip accelerometers for a week. The team also assessed body composition and food intake. As expected, they found that older participants moved less and more slowly, while carrying more body fat<\/strong><\/span>. However, the goal of this experiment was not to state the obvious. The researchers then compared younger and older mice using similar \u201cscorecards,\u201d and found that age-related differences in mice match those in humans closely enough to make mice a reasonable model for investigating the biology behind those differences. The researchers then administered d-fenfluramine, which promotes serotonin release and inhibits its reuptake<\/strong><\/span>. The treatment reduced movement, distance, and speed<\/span> during the dark phase (when mice are normally most active). It also briefly suppressed feeding, reduced energy expenditure, and shifted fuel use toward fat<\/span>, recapitulating age-related changes<\/span><\/strong><\/span>. Since the drug works broadly, the researchers had to identify the specific neuronal populations involved. They focused on two brain regions: the dorsal raphe, a brainstem region containing serotonin-producing neurons, and the ventral tegmental area (VTA), a region rich in dopamine-producing neurons, which are involved in motivation, reward, and movement. The team examined dorsal raphe neurons in brain slices from younger and older mice and found no age-related difference in the number of serotonin neurons. However, the firing patterns were different: older animals\u2019 neurons fired more during the dark phase, when mice are active, and less during the light phase relative to younger animals. The researchers then selectively stimulated serotonin-producing neurons in the dorsal raphe to make them fire more frequently. In young mice, this reduced movement, distance traveled, and average speed while increasing inactivity<\/strong><\/span>.”<\/p>\n

“…The researchers then knocked out 5-HT2C<\/span>, one of the receptors through which serotonin acts<\/strong><\/span>, in 12- to 14-month-old mice. The knockout animals traveled farther, moved faster, and spent less time inactive<\/strong><\/span> \u2013 again, with no changes to food intake, fuel use, or energy expenditure.”<\/p>\n

“…The researchers suspected that serotonin produced by neurons in dorsal raphe activates these inhibitory neurons, which would then suppress dopamine-producing neurons in the VTA. Since dopamine normally helps promote movement and motivation [3] inhibiting dopamine-producing neurons could produce the effects observed<\/strong><\/span> by the researchers in their experiments. Electrical recordings supported this idea: serotonin increased the frequency of inhibitory signals received by dopamine neurons<\/span>. Decreasing and increasing the receptors\u2019 activity also produced results in support of the hypothesis<\/strong><\/span>.”<\/p>\n","protected":false},"excerpt":{"rendered":"

One of the rare studies that truly shines the light on just how systemically nefarious 5-HT is….<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2],"tags":[192,594,1567,97,2271,319,47,191],"class_list":["post-3145","post","type-post","status-publish","format-standard","hentry","category-science","tag-5-ht","tag-dopamine","tag-endurance","tag-metabolism","tag-motivation","tag-obesity","tag-serotonin","tag-ssri","wpcat-2-id"],"_links":{"self":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/3145","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3145"}],"version-history":[{"count":3,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/3145\/revisions"}],"predecessor-version":[{"id":3148,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/3145\/revisions\/3148"}],"wp:attachment":[{"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3145"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3145"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3145"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}