Scientists at Baylor College of Medicine, the National Institutes of Health and Virginia Tech Carilion Research Institute have discovered a new mechanism in the mouse brain that regulates obesity. The study shows that this new mechanism can potentially be targeted to treat obesity.<\/p>\n
\u201cIt\u2019s well known that the brain is involved in the development of obesity, but how a high-fat diet changes the brain so it triggers the accumulation of body fat is still unclear,\u201d said senior author Dr. Makoto Fukuda, assistant professor of paediatrics at Baylor and the USDA\/ARS Children\u2019s Nutrition Research Center at Baylor and Texas Children\u2019s Hospital.<\/p>\n
Fukuda and colleagues studied the mouse Rap1 gene, which is expressed in a variety of tissues, including the brain where it is involved in functions such as memory and learning. Little was known, however, of the role brain Rap1 plays in energy balance.<\/p>\n
To explore the role Rap1 plays in a mouse model, the scientists selectively deleted the Rap1 gene in a group of neurons in the hypothalamus, a region of the brain that is involved in regulating whole-body metabolism.<\/p>\n
The scientists had two groups of mice. In one group, the mice were genetically engineered to lack the Rap1 gene, while the control group had a functional Rap 1 gene. Then, the scientists fed the mice in both groups a high-fat diet in which 60 percent of the calories came from fat. As expected, the control mice with a working Rap1 gene gained weight, but, in comparison, the mice that lacked Rap 1 had markedly reduced body weight and less body fat. Interestingly, when both groups of mice were fed a normal diet, both showed similar weights and body fat. <\/p>\n
The scientists then looked closer at why the mice lacking the Rap1 gene had not gained weight despite eating a high-fat diet.
\n\u201cWe observed that the mice lacking Rap1 were not more physically active. However, they ate less and burned more body fat than mice with Rap1,\u201d said Fukuda. \u201cThese observations were associated with the hypothalamus producing more of a hormone that reduces appetite, called POMC, and less of hormones that stimulate appetite, called NPY and AgRP.\u201d These mice also had lower levels of blood glucose and insulin than controls.
\nThe scientists also were interested in studying whether leptin changed in mice lacking Rap1. Leptin, the \u2018satiety hormone\u2019 produced by fatty tissue, helps regulate body weight by inhibiting appetite. Obese people, however, do not respond to leptin\u2019s signals of satiety, and the blood levels of leptin are higher than those in non-obese people. Leptin resistance is a hallmark of human obesity.<\/p>\n
Mice that lacked Rap1 and ate a high-fat diet, on the other hand, did not develop leptin resistance; they were able to respond to leptin, and this was reflected in the hormone\u2019s lower blood levels.<\/p>\n
Fukuda and colleagues also tested the effect of inhibiting Rap1 with drugs instead of deleting the gene on mice on a high-fat diet. The scientists inhibited RAP1 action with inhibitor ESI-05.<\/p>\n
\u201cWhen we administered ESI-05 to obese mice, we restored their sensitivity to leptin to a level similar to that in mice eating a normal diet. The mice ate less and lost weight,\u201d said Fukuda.<\/p>\n
The scientists have shown a new mechanism by which the brain can affect the development of obesity triggered by consuming a high-fat diet. Consuming a high-fat diet results in changes in the brain that increase Rap1 activity, which in turn leads to a decreased sensitivity to leptin, and this sets the body on a path to obesity.
\n\u201cThis new mechanism involving Rap1 in the brain may represent a potential therapeutic target for treating human obesity in the future,\u201d said Fukuda.<\/p>\n
Baylor College of Medicine\nwww.bcm.edu\/news\/nutrition\/rap1-potential-new-target-to-treat-obesity<\/link>\n","protected":false},"excerpt":{"rendered":"
Scientists at Baylor College of Medicine, the National Institutes of Health and Virginia Tech Carilion Research Institute have discovered a new mechanism in the mouse brain that regulates obesity. The study shows that this new mechanism can potentially be targeted to treat obesity. \u201cIt\u2019s well known that the brain is involved in the development of […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1187"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=1187"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1187\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=1187"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=1187"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=1187"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}