Original ResearchFull Report: Clinical—LiverIncreased De Novo Lipogenesis Is a Distinct Characteristic of Individuals With Nonalcoholic Fatty Liver Disease
Section snippets
Subjects and Methods
The methods are briefly described here and have been reported previously.14, 31, 32 A detailed description of the study design, laboratory procedures, and calculations is provided in Supplementary Methods. Research subjects were recruited from local community health fairs and physician referrals to determine the role of metabolic syndrome in the development of NAFLD.1 The initial screening criteria included characteristics of metabolic syndrome,33 and liver enzyme levels were measured to
Results
Subjects were separated phenotypically as having LowLF or HighLF1 (Table 1). The LowLF and HighLF groups were matched for anthropometric and plasma biochemistry data except for fasting insulin concentrations, which were higher in the HighLF group, as expected.39 This higher level of insulin resulted in a greater calculated AdipoIR, an index of adipose insulin resistance,6 in subjects with HighLF (Table 1). Given the differences in body composition, anthropometric variables for men and women
Discussion
The present study represents the first direct confirmation of the significant role of de novo lipogenesis in the etiology of fatty liver disease. Compared with subjects with LowLF, those with HighLF had a doubling of the fractional contribution from de novo lipogenesis to VLDL-FA (10.1% ± 6.7% vs 23.2% ± 7.9%, respectively; P < .001), a 3-fold higher rate of production of VLDL-TG from lipogenesis, accounted for through extended labeling of the lipogenic pathway, and a positive association
Acknowledgments
The authors thank the research subjects for their participation; the staff of the Clinical and Translational Research Center and Dora Bradford, RN-C, WHNP, for recruitment and screening of the subjects and excellent patient care; Maressa Valdez, RD, for subject recruitment, clinical coordination, and data collection; Joseph Lee, BS, Yelena Hovhannisyan, MS, and Kimberly Borke, MD, for data generation, analysis, and management; Drs Jay Horton and Scott Grundy for support; Dr Elizabeth Murphy for
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Author names in bold designate shared co-first authorship.
Conflicts of interest The authors disclose no conflicts.
Funding Supported by National Institutes of Health (NIH) grant RL1DK081187 (to E.J.P.), the Task Force for Obesity Research at UT Southwestern/NIH grant UL1DE019584, and the Clinical Translational Science Award, National Center for Advancing Translational Sciences/NIH grant UL1-RR024982.