{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Xiao S"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS"],"pubmed_abstract":["Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. The mechanisms that mediate metformin's effects on energy balance remain incompletely defined. Here we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite Lac-Phe in mice as well as in two independent human cohorts. In cell culture, metformin drives Lac-Phe biosynthesis via inhibition of complex I, increased glycolytic flux, and intracellular lactate mass action. Other biguanides and structurally distinct inhibitors of oxidative phosphorylation also increase Lac-Phe levels <i>in vitro</i>. Genetic ablation of CNDP2, the principal biosynthetic enzyme for Lac-Phe, in mice renders animals resistant to metformin's anorexigenic and anti-obesity effects. Mediation analyses "],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.11.02.565321"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10635077"],"repository":["biostudies-literature"],"pubmed_title":["Lac-Phe mediates the anti-obesity effect of metformin."],"pmcid":["PMC10635077"],"funding_grant_id":["UL1 TR001420","K08 HL145095","UL1 TR001881","N01 HC095166","N01 HC095165","N01 HC095168","N01 HC095167","N01 HC095169","75N92020D00007","N01 HC095160","N01 HC095162","N01 HC095161","N01 HC095164","N01 HC095163","75N92020D00001","75N92020D00002","P30 DK040561","75N92020D00005","75N92020D00006","75N92020D00003","75N92020D00004","UL1 TR000040","HHSN268201500003C","UL1 TR001079","N01 HC095159","R01 HL151855","UM1 DK078616","P30 DK063491","R01 HL105756","HHSN268201500003I"],"pubmed_authors":["Deng S","Gerszten RE","Rotter JI","Li VL","Guo X","Lyu X","Chen ZZ","Rich SS","Clish CB","Wei W","Shi X","Farrell L","Tiwari G","Long JZ","Ida Chen YD","Chen X","Tahir UA","Knowles JW","Taylor KD","Benson MD","Wood AC","Zheng S","Abbasi F","Xiao S","Goodarzi MO","Lange LA"],"additional_accession":[]},"is_claimable":false,"name":"Lac-Phe mediates the anti-obesity effect of metformin.","description":"Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. The mechanisms that mediate metformin's effects on energy balance remain incompletely defined. Here we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite Lac-Phe in mice as well as in two independent human cohorts. In cell culture, metformin drives Lac-Phe biosynthesis via inhibition of complex I, increased glycolytic flux, and intracellular lactate mass action. Other biguanides and structurally distinct inhibitors of oxidative phosphorylation also increase Lac-Phe levels <i>in vitro</i>. Genetic ablation of CNDP2, the principal biosynthetic enzyme for Lac-Phe, in mice renders animals resistant to metformin's anorexigenic and anti-obesity effects. Mediation analyses ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2026-06-08T03:27:25.587Z","creation":"2026-06-08T03:14:21.513Z"},"accession":"S-EPMC10635077","cross_references":{"pubmed":["37961394"],"doi":["10.1101/2023.11.02.565321"]}}