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Is pre-heparin hepatic triglyceride lipase useful tounderstand the mechanisms of dyslipidemia?

Makoto Kurano

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Kurano M, Is pre-heparin hepatic triglyceride lipase useful tounderstand the mechanisms of dyslipidemia?. Lab Med Int 2022; 1(1): 4-5. doi: 10.51041/lmi.1.1_4

Editorial
Lab Med Int 2022; 1(1): 4-5

Correspondence: Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
E-mail: kurano-tky”@”umin.ac.jp
*Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo


In the paper entitled “Association of pre-heparin plasma hepatic triglyceride lipase with lipoprotein subspecies in type 2 diabetes, Comparison with lipoprotein lipase” in this issue of the Laboratory Medicine International, Nagaike et al. measured pre-heparin hepatic triglyceride lipase (HTGL) as well as pre-heparin lipoprotein lipase (LPL) in 120 Japanese diabetic subjects 1).
The absolute levels of HTGL and LPL are usually evaluated after injection with heparin, because HTGL and LPL exist on the surface of the liver sinusoidal capillaries 2) and capillary endothelial cells 3), respectively. To investigate the existence of gene deletion or heterogenous insufficiency in the patients with severe hypertriglyceridemia, the evaluation of total mass of HTGL and LPL is important. However, HTGL and LPL should be involved in the pathogenesis of dyslipidemia in patients with milder hypertriglyceridemia. Moreover, the activities of lipases have been reported to be lower in diabetic patients 4) who usually suffer from dyslipidemia characterized with high remnant lipoproteins and low HDL 5). Therefore, the investigation on the association of these lipases and lipoprotein profiles has been expected to understand the mechanisms of dyslipidemia and to consider future application of laboratory tests of the lipases for the diagnosis of dyslipidemia.
In this study, the authors investigated pre-heparin HTGL and LPL level instead of post-heparin HTGL and LPL activities. Although this point may be a major limitation in the interpretation of the results to understand the mechanisms for dyslipidemia observed in diabetic patients, I think that this question is worth investigating since the usefulness of pre-heparin HTGL and LPL levels in clinical laboratory medicine is a controversial at present. They demonstrated that pre-heparin HTGL levels had no significant association with remnant-like particle(RLP)-C or subspecies of LDL-C and HDL-C, while pre-heparin LPL levels had significant a positive association with RLP-C and negative ones with HDL-C. They hypothesized that the weaker associations of HTGL with lipoprotein fractions might be due to the fact that in pre-heparin conditions, smaller percentage of HTGL mass was detected compared with LPL 6) 7).
Although this study could not demonstrate the usefulness of pre-heparin HTGL measurement, negative results in this study will be important when specific modulation of pre-heparin HTGL levels in some unique pathological conditions will be identified in the future. I expect future studies with primary dyslipidemia caused by genetic factors such as familial combined hyperlipidemia and moderate hypertriglyceridemia caused by alcohol overconsumption.

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Reference

  1. Hiroe Nagaike, Toshiyuki Hayashi, Yasuki Ito, et al. Association of pre-heparin plasma hepatic triglyceride lipase with lipoprotein subspecies in type 2 diabetes, Comparison with lipoprotein lipase. LMI 2022; 1(1): 6-12.
  2. Brunzell JD, Zambon A, Deeb SS. The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype. Biochim Biophys Acta 2012; 1821(3): 365-72. PubMed 
  3. Kersten S. Physiological regulation of lipoprotein lipase. Biochim Biophys Acta 2014; 1841(7): 919-33. PubMed
  4. Shirakawa T, Nakajima K, Yatsuzuka S, et al. The role of circulating lipoprotein lipase and adiponectin on the particle size of remnant lipoproteins in patients with diabetes mellitus and metabolic syndrome. Clin Chim Acta 2015; 440: 123-32. PubMed
  5. Hirano T. Pathophysiology of Diabetic Dyslipidemia. J Atheroscler Thromb 2018; 25(9): 771-82.
  6. Nishimura M, Iwanaga T, Ohkaru Y, et al. Change in immunoreactive human hepatic triglyceride lipase (HTGL) mass and the shelf-life of the HTGL ELISA kit in long-term storage. J Immunoassay Immunochem 2006; 27(1): 89-102. PubMed
  7. Hirano T, Nishioka F, Murakami T. Measurement of the serum lipoprotein lipase concentration is useful for studying triglyceride metabolism: Comparison with postheparin plasma. Metabolism 2004; 53(4): 526-31. PubMed
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