Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets123

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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 (≤ 85 pmol/L) lean (n = 9) and obese (n = 6) and hyperinsulinemic (≥ 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.

KEY WORDS

Obesity
hyperinsulinemia
hepatic de novo lipogenesis
triacylglycerols
triglycerides
hypertriglyceridemia
hyperlipidemia
cardiovascular disease
heart disease

Cited by (0)

1

From the Department of Nutritional Sciences and Toxicology, University of California, Berkeley (J-MS and KA), and the Department of Medicine, University of California, San Francisco (J-MS, PL, and DD).

2

Supported in part by the American Heart Association (no. 97-30-202N), the US Department of Agriculture, and the American Diabetes Association (Clinical Research Award). A National Institutes of Health grant (RR00083-37) from the Division of Research Resources supported the General Clinical Research Center at San Francisco General Hospital.

3

Address reprint requests to J-M Schwarz, Department of Nutritional Sciences and Toxicology, 119 Morgan Hall, University of California Berkeley, Berkeley, CA 94720-3104. E-mail:[email protected].