Cited by 496Lipid metabolism and disordersLipid metabolism and biosynthesisDiet, Metabolism, and Disease

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Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets

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Schwarz, Jean-Marc, Linfoot, Peter, Dare, Doris, Aghajanian, Karmen·2003·The American Journal of Clinical Nutrition

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Abstract

Background Hypertriglyceridemia is associated with increased risk of cardiovascular disease. Until recently, the importance of hepatic de novo lipogenesis (DNL) in contributing to hypertriglyceridemia was difficult to assess because of methodologic limitations.Objective We evaluated the extent of the contribution by DNL to different conditions associated with hypertriglyceridemia.Design After 5 d of an isoenergetic high-fat, low-carbohydrate diet, fasting DNL was measured in normoinsulinemic (<or= 85 pmol/L) lean (n = 9) and obese (n = 6) and hyperinsulinemic (>or= 115 pmol/L) obese (n = 8) subjects. Fasting DNL was measured after a low-fat, high-carbohydrate diet in normoinsulinemic lean (n = 5) and hyperinsulinemic obese (n = 5) subjects. Mass isotopomer distribution analysis was used to measure the fraction of newly synthesized fatty acids in VLDL-triacylglycerol.Results With the high-fat, low-carbohydrate diet, hyperinsulinemic obese subjects had a 3.7-5.3-fold higher fractional DNL (8.5 +/- 0.7%) than did normoinsulinemic lean (1.6 +/- 0.5%) or obese (2.3 +/- 0.3%) subjects. With the low-fat, high-carbohydrate diet, normoinsulinemic lean and hyperinsulinemic obese subjects had similarly high fractional DNL (13 +/- 5.1% and 12.8 +/- 1.4%, respectively). Compared with baseline, consumption of the high-fat, low-carbohydrate diet did not affect triacylglycerol concentrations. However, after the low-fat, high-carbohydrate diet, triacylglycerols increased significantly and DNL was 5-6-fold higher than in normoinsulinemic subjects consuming a high-fat diet. The increase in triacylglycerol after the low-fat, high-carbohydrate diet was correlated with fractional DNL (P < 0.01), indicating that subjects with high DNL had the greatest increase in triacylglycerols.Conclusions These results support the concept that both hyperinsulinemia and a low-fat diet increase DNL, and that DNL contributes to hypertriglyceridemia.

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Authors: Schwarz, J.-M., Linfoot, P., Dare, D., & Aghajanian, K.
Affiliations: University of California, San Francisco (US)
Corresponding author: Schwarz, Jean-Marc
Venue: The American Journal of Clinical Nutrition
Publisher: Elsevier BV
Published: 2003-01
Volume: 77
Issue: 1
Pages: 43-50
ISSN: 0002-9165 (ISSN-L)
DOI: 10.1093/ajcn/77.1.43
OpenAlex: W2141823673
Cited by: 496
References: 39
Citations by year: 2026: 5 · 2025: 21 · 2024: 17 · 2023: 17 · 2022: 25 · 2021: 21 · 2020: 32 · 2019: 30 · 2018: 22 · 2017: 23 · 2016: 32 · 2015: 32 · 2014: 24 · 2013: 25 · 2012: 21
FWCI: 10.14
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 7358 d)
Locations: American Journal of Clinical Nutrition (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (2m01rr000083-41)
National Center for Research Resources (RR00083-37)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords: hepatic de novo lipogenesis, hypertriglyceridemia, hyperinsulinemia, low-carbohydrate high-fat diet, low-fat high-carbohydrate diet, triglycerides, obesity, mass isotopomer distribution analysis, dietary fat
MeSH terms: Adult, Dietary Carbohydrates, Dietary Fats, Humans, Hyperinsulinism, Lipids, Liver, Male, Middle Aged, Obesity, Hypertriglyceridemia, Body Mass Index

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Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets

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