Cell. 2025 Jan 9;188(1):175-186.e20. doi: 10.1016\/j.cell.2024.10.032.
Epub 2024 Nov 12. PMID: 39536746<\/a><\/p>\n\n\n\nAbstract<\/strong>
\u03b2-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known
pathways of BHB metabolism involve the interconversion of BHB and
primary energy intermediates. Here, we identify a previously undescribed
BHB secondary metabolic pathway via CNDP2-dependent enzymatic
conjugation of BHB and free amino acids. This BHB shunt pathway
generates a family of anti-obesity ketone metabolites, the BHB-amino
acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid
BHB-ylation activity and reduces BHB-amino acid levels. The most
abundant BHB-amino acid, BHB-Phe, is a ketosis-inducible congener of Lac
-Phe that activates hypothalamic and brainstem neurons and suppresses
feeding. Conversely, CNDP2-KO mice exhibit increased food intake and
body weight following exogenous ketone ester supplementation or a
ketogenic diet. CNDP2-dependent amino acid BHB-ylation and BHB-amino
acid metabolites are also conserved in humans. Therefore, enzymatic
amino acid BHB-ylation defines a ketone shunt pathway and bioactive
ketone metabolites linked to energy balance.<\/p>\n","protected":false},"excerpt":{"rendered":"\u660e\u65e56\/11\u62c5\u5f53\u306e\u91ce\u53e3\uff08\u795e\u7d4c\u79d1\u5b66\u7814\u7a76\u90e8 \u8a2a\u554f\u7814\u7a76\u54e1\/\u6771\u4eac\u30ac\u30b9\u30b0\u30eb\u30fc\u30d7 \u7523\u696d\u533b\uff09\u3067\u3059\u3002\u3000\u660e\u65e5\u306f\u3001\u4e0b\u8a18\u306e\u8ad6\u6587\u3092\u7d39\u4ecb\u3055\u305b\u3066\u9802\u304f\u4e88\u5b9a\u3067\u3059\u3002 A beta-hydroxybutyrate shunt pathway generat…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[3],"tags":[],"class_list":["post-420","post","type-post","status-publish","format-standard","hentry","category-journal-club"],"jetpack_sharing_enabled":true,"jetpack_featured_media_url":"","_links":{"self":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/420","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=420"}],"version-history":[{"count":2,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/420\/revisions"}],"predecessor-version":[{"id":422,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/420\/revisions\/422"}],"wp:attachment":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=420"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=420"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=420"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}