Diacylglycerol oil for apolipoprotein C-II deficiency
Sir,Apolipoprotein C-II is a cofactor of lipoprotein lipase (LPL), which hydrolyses triglycerides of chylomicrons and very low-density lipoproteins (VLDLs).1 We report our therapeutic experience with diacylglycerol (DAG) oil, a natural edible oil, in a patient with apolipoprotein C-II deficiency, a rare, autosomal, recessively-inherited disease.
A 43-year-old Japanese man presented with hypertriglyceridaemia, chylomicronaemia, hepatosplenomegaly, postprandial epigastric pain, and recurrent attacks of pancreatitis. Fasting serum triglyceride fluctuated from 545 to 2252 mg/dl, even on treatment with fibrate and ethyl icosapentate, indicating refractory hypertriglyceridaemia. On admission, levels of fasting serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, plasma glucose, and haemoglobin A1c were 317, 33, 28, 2252, 107 mg/dl and 5.0%, respectively. Serum apolipoprotein C-II and post-heparin LPL levels were 0.5 mg/dl (normal range, 2.2–5.0 mg/dl) and 486 µg/l (normal range 130–350 µg/l), respectively, which was compatible with apolipoprotein C-II deficiency.
A diet restricted in fat (10 g) and energy (900 kcal) reduced serum triglyceride levels to 230 mg/dl at 3 weeks after admission. The dietary substitution of DAG for triacylglycerol (TAG) has been found to ameliorate postprandial hyperlipidaemia.2 Therefore, after informed consent, the patient was subjected to a loading test with 10 g of DAG or TAG oil after a 15-h fast, in a cross-over style with a 1-week interval. The TAG oil was prepared to give a final fatty acid composition similar to that of the DAG oil. Samples were obtained every 2 h (hours 0–8) to measure serum triglyceride, free fatty acid (FFA), remnant-like particle (RLP)-cholesterol, and VLDL-cholesterol.
Serum FFA gradually increased after ingestion of both kinds of oil, with no difference (Figure 1A). Serum triglycerides were remarkably increased by TAG from hour 4; the increase with DAG was almost half of that with TAG at hours 4 and 6 (Figure 1B). Serum VLDL-cholesterol was decreased by DAG up to hour 6 after oil ingestion, while TAG increased VLDL-cholesterol continuously (Figure 1C). Serum RLP-cholesterol was linearly elevated by TAG from hours 2 to 8, but the increment by DAG was modest (Figure 1D).
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The main digestive product of DAG is 1-monoacylglycerol, which is poorly re-esterified into TAG in the small intestinal mucosa, while the main product of TAG digestion is 2-monoacylglycerol, which is easily re-esterified to form triglyceride and incorporated into chylomicrons.3 These properties of DAG may be beneficial in improving postprandial hyperlipidaemia. An increase in postprandial energy expenditure is also thought to be one of the underlying mechanisms in the suppression of postprandial hyperlipidaemia by DAG.4 DAG has been reported to up-regulate mRNA expressions associated with fatty acid transport, mitochondrial and peroxisomal ß-oxidation, and thermogenesis in the small intestine.5
In our study, DAG ingestion suppressed postprandial increase in serum triglyceride, and triglyceride-rich lipoprotein-derived cholesterol in a subject with apolipoprotein C-II deficiency. Therapeutic interventions in apolipoprotein C-II deficiency (stringently restricted diets, blood transfusion6) are currently very limited. DAG may be a promising addition to therapeutic options in this difficult disease.
Department of Internal Medicine
The Jikei University School of Medicine
Chiba
Japan
Department of Internal Medicine
The Jikei University School of Medicine
Chiba
Japan
Department of Laboratory Medicine
The Jikei University School of Medicine
Chiba
Japan
Josai University, Saitama
Japan
email: yanaih{at}jikei.ac.jp
Acknowledgements
This study was supported by the Jikei University Research Fund.
References
1. Breckenridge WC, Alaupovic P, Cox DW, Little JA. (1982) Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency. Atherosclerosis 44 223–35.[CrossRef][ISI][Medline]
2. Tada N, Watanabe H, Matsuo N, Tokimitsu I, Okazaki M. (2001) Dynamics of postprandial remnant-like lipoprotein particles in serum after loading of diacylglywcerols. Clin Chim Acta 311 109–17.[CrossRef][ISI][Medline]
3. Tada N. (2004) Physiological actions of diacylglycerol outcome. Curr Opin Clin Nutr Metab Care 7 145–9.[CrossRef][ISI][Medline]
4. Saito S, Tomonobu K, Hase T, Tokimitsu I. (2006) Effects of diacylglycerol on postprandial energy expenditure and respiratory quotient in healthy subjects. Nutrition 22 30–5.[CrossRef][ISI][Medline]
5. Murase T, Nagasawa A, Suzuki J, Wakisaka T, Hase T, Tokimitsu I. (2002) Dietary alpha-linolenic acid-rich diacylglycerols reduce body weight gain accompanying the stimulation of intestinal beta-oxidation and related gene expressions in C57BL/KsJ-db/db mice. J Nutr 132 3018–22.
6. Breckenridge WC, Little JA, Steiner G, Chow A, Poapst M. (1978) Hypertriglyceridemia associated with deficiency of apolipoprotein C-II. N Engl J Med 298 1265–73.[Abstract]
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