The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue

Autor: Rebecca C. Schugar, Diana M. Shih, Manya Warrier, Robert N. Helsley, Amy Burrows, Daniel Ferguson, Amanda L. Brown, Anthony D. Gromovsky, Markus Heine, Arunachal Chatterjee, Lin Li, Xinmin S. Li, Zeneng Wang, Belinda Willard, YongHong Meng, Hanjun Kim, Nam Che, Calvin Pan, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Richard E. Morton, Carl D. Langefeld, Swapan K. Das, Lawrence L. Rudel, Nizar Zein, Arthur J. McCullough, Srinivasan Dasarathy, W.H. Wilson Tang, Bernadette O. Erokwu, Chris A. Flask, Markku Laakso, Mete Civelek, Sathyamangla V. Naga Prasad, Joerg Heeren, Aldons J. Lusis, Stanley L. Hazen, J. Mark Brown
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Cell Reports, Vol 19, Iss 12, Pp 2451-2461 (2017)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2017.05.077
Popis: Summary: Emerging evidence suggests that microbes resident in the human intestine represent a key environmental factor contributing to obesity-associated disorders. Here, we demonstrate that the gut microbiota-initiated trimethylamine N-oxide (TMAO)-generating pathway is linked to obesity and energy metabolism. In multiple clinical cohorts, systemic levels of TMAO were observed to strongly associate with type 2 diabetes. In addition, circulating TMAO levels were associated with obesity traits in the different inbred strains represented in the Hybrid Mouse Diversity Panel. Further, antisense oligonucleotide-mediated knockdown or genetic deletion of the TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) conferred protection against obesity in mice. Complimentary mouse and human studies indicate a negative regulatory role for FMO3 in the beiging of white adipose tissue. Collectively, our studies reveal a link between the TMAO-producing enzyme FMO3 and obesity and the beiging of white adipose tissue. : Microbes resident in the human intestine represent a key transmissible environmental factor contributing to obesity and related disorders. Schugar et al. now show that expression of the TMAO-producing enzyme FMO3 is linked to obesity and energy expenditure in both mice and humans. Keywords: microbiota, nutrition, obesity, diabetes, adipose, flavin-containing monooxygenase 3, FMO3
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