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Measurement of lipogenic flux by deuterium resolved mass spectrometry.
Fu, Xiaorong; Deja, Stanislaw; Fletcher, Justin A; Anderson, Norma N; Mizerska, Monika; Vale, Gonçalo; Browning, Jeffrey D; Horton, Jay D; McDonald, Jeffrey G; Mitsche, Matthew A; Burgess, Shawn C.
Affiliation
  • Fu X; Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Deja S; Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Fletcher JA; Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Anderson NN; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Mizerska M; Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Vale G; Department of Clinical Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Browning JD; Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Horton JD; Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • McDonald JG; Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Mitsche MA; Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Burgess SC; Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Commun ; 12(1): 3756, 2021 06 18.
Article in En | MEDLINE | ID: mdl-34145255
ABSTRACT
De novo lipogenesis (DNL) is disrupted in a wide range of human disease. Thus, quantification of DNL may provide insight into mechanisms and guide interventions if it can be performed rapidly and noninvasively. DNL flux is commonly measured by 2H incorporation into fatty acids following deuterated water (2H2O) administration. However, the sensitivity of this approach is limited by the natural abundance of 13C, which masks detection of 2H by mass spectrometry. Here we report that high-resolution Orbitrap gas-chromatography mass-spectrometry resolves 2H and 13C fatty acid mass isotopomers, allowing DNL to be quantified using lower 2H2O doses and shorter experimental periods than previously possible. Serial measurements over 24-hrs in mice detects the nocturnal activation of DNL and matches a 3H-water method in mice with genetic activation of DNL. Most importantly, DNL is detected in overnight-fasted humans in less than an hour and is responsive to feeding during a 4-h study. Thus, 2H specific MS provides the ability to study DNL in settings that are currently impractical.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Triglycerides / Lipogenesis / Fatty Acids / Liver / Gas Chromatography-Mass Spectrometry Limits: Animals Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Triglycerides / Lipogenesis / Fatty Acids / Liver / Gas Chromatography-Mass Spectrometry Limits: Animals Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Type: Article Affiliation country: United States