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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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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Reduction in dietary intake of fat is frequently associated with increased intake of carbohydrates and leads to carbohydrate induced hypertriglyceridemia (HPTG).
“Reduction in dietary intake of fat is frequently associated with increased intake of carbohydrates and leads to carbohydrate induced hypertriglyceridemia (HPTG) [64-69].”
From The case for low carbohydrate diets in diabetes management (2005) · cites this paper as [67]
Carbohydrate-induced hypertriglyceridemia involves both increased triglyceride synthesis and decreased fractional triglyceride clearance, with a possible contribution from increased hepatic de novo fatty acid synthesis.
“both increase in TG synthesis and decrease in fractional TG clearance have been demonstrated [64-66] with a possible contribution from increased hepatic de novo fatty acid synthesis [64,67].”
From The case for low carbohydrate diets in diabetes management (2005) · cites this paper as [67]
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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)
- 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
- 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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