Lipoprotein lipase and atherosclerosis

Kobayashi, Junji; Nagashima, Izumi; Taira, Koichi; Hikita, Minoru; Bujo, Hideaki; Morisaki, Naho; Saitō, Yasushi

doi:10.5551/jat1973.26.3_123

Cited by 10 publications

(15 citation statements)

References 30 publications

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“…In the present in vivo and in vitro studies, the increased LPL expression in HSCs enhanced cholesterol uptake from serum lipoproteins into HSCs in an autocrine manner, independent of LPL activity. LPL is known to be a lipase with a key role in hydrolyzing TGs from TG‐rich lipoproteins, whereas many reports have shown that it has an additional bridging function, promoting the binding of different lipoproteins to their receptors, independent of its enzyme activity . LPL enhances lipoprotein uptake into various cells by pathways that are independent of LPL enzyme activity but require LPL as a molecular bridge between lipoproteins and heparan sulfate proteoglycans (HSPGs) or lipoprotein receptors .…”

Section: Discussionmentioning

confidence: 99%

“…LPL hydrolyzes triglycerides (TGs) from serum lipoproteins and functions in incorporating free fatty acids (FFAs) produced as a result of hydrolysis in each tissue. In recent years, LPL has also been reported to promote the binding of lipoproteins to their receptors, and its involvement in diseases associated with atherosclerosis has been noted . Furthermore, its role in many aspects of obesity, such as insulin resistance and dyslipidemia, has also been reported .…”

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confidence: 97%

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Lipoprotein Lipase Up‐regulation in Hepatic Stellate Cells Exacerbates Liver Fibrosis in Nonalcoholic Steatohepatitis in Mice

et al. 2019

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Lipoprotein lipase (LPL) plays a central role in incorporating plasma lipids into tissues and regulates lipid metabolism and energy balance in the human body. Conversely, LPL expression is almost absent in normal adult livers. Therefore, its physiological role in the liver remains unknown. We aimed to elucidate the role of LPL in the pathophysiology of nonalcoholic steatohepatitis (NASH), a hepatic manifestation of obesity. Hepatic stellate cell (HSC)–specific LPL‐knockout (LplHSC‐KO) mice, LPL‐floxed (Lplfl/fl) mice, or double‐mutant toll‐like receptor 4–deficient (Tlr4−/−) LplHSC‐KO mice were fed a high‐fat/high‐cholesterol diet for 4 weeks to establish the nonalcoholic fatty liver model or an high‐fat/high‐cholesterol diet for 24 weeks to establish the NASH model. Human samples, derived from patients with nonalcoholic fatty liver disease, were also examined. In human and mouse NASH livers, serum obesity‐related factors, such as free fatty acid, leptin, and interleukin‐6, dramatically increased the expression of LPL, specifically in HSCs through signal transducer and activator of transcription 3 signaling, as opposed to that in hepatocytes or hepatic macrophages. In the NASH mouse model, liver fibrosis was significantly reduced in LplHSC‐KO mice compared with that in Lplfl/fl mice. Nonenzymatic LPL‐mediated cholesterol uptake from serum lipoproteins enhanced the accumulation of free cholesterol in HSCs, which amplified TLR4 signaling, resulting in the activation of HSCs and progression of hepatic fibrosis in NASH. Conclusion: The present study reveals the pathophysiological role of LPL in the liver, and furthermore, clarifies the pathophysiology in which obesity, as a background factor, exacerbates NASH. The LPL‐mediated HSC activation pathway could be a promising therapeutic target for treating liver fibrosis in NASH.

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Section: Discussionmentioning

confidence: 99%

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confidence: 97%

Lipoprotein Lipase Up‐regulation in Hepatic Stellate Cells Exacerbates Liver Fibrosis in Nonalcoholic Steatohepatitis in Mice

et al. 2019

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“…LPL and EL concentrations were measured by ELISA as reported previously (12,14,15). HTGL activities were measured using the method reported previously (9, 10).…”

Section: Other Methodsmentioning

confidence: 99%

A new enzyme-linked immunosorbent assay system for human serum hepatic triglyceride lipase

Miyashita

Nakajima

Fukamachi

et al. 2017

Journal of Lipid Research

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There is no established method for measuring human hepatic triglyceride (TG) lipase (HTGL) concentration in serum. In this study, we developed new monoclonal Abs (MoAbs) (9A1 mouse MoAb and 141A1 rat MoAb) that react with HTGL both in serum and in postheparin plasma (PHP) and established a novel ELISA system for measuring serum HTGL and PHP-HTGL concentrations. To confirm the specificity of MoAbs, we performed immunoprecipitation-immunoblotting analysis. Both 9A1 mouse MoAb and 141A1 rat MoAb were able to immunoprecipitate not only recombinant HTGL and PHP-HTGL but also serum HTGL, demonstrating that HTGL exists in serum obtained without heparin injection. This method yielded intra- and interassay coefficients of variation of <6% and showed no cross-reactivity with LPL or endothelial lipase. In clinical analysis on 42 male subjects with coronary artery disease, there were strong positive correlations of serum HTGL concentration to PHP-HTGL concentration ( = 0.727, < 0.01). Serum HTGL concentrations showed positive correlations to serum TGs ( = 0.314, < 0.05) and alanine aminotransferase ( = 0.406, < 0.01), and tendencies toward positive correlations to LDL cholesterol, small dense LDL, and γGTP. These results suggest that this new ELISA method for measuring serum HTGL is applicable in daily clinical practice.

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“…18 LPL is the major enzyme responsible for the hydrolysis of TG-rich lipoprotein in circulating lipoproteins. 5 Genetic defects in LPL are responsible for the reduction in TG-rich lipoprotein clearance, and mutations in the LPL gene play important roles in the development of hypertriglyceridemia in the general population. [20][21][22][23] To date, approximately 143 different mutations have been found in the human LPL gene, 90% of which occur in the coding regions and affect LPL functions through catalytic activity, dimerization, secretion, and heparin bonding.…”

Section: Discussionmentioning

confidence: 99%

“…4 Lipoprotein lipase (LPL) is the major enzyme responsible for the hydrolysis of the TG-rich lipoprotein of circulating lipoproteins. 5 LPL has an important function in TG metabolism; LPL deficiency would result in hypertriglyceridemia. [6][7][8] Several genome-wide association studies (GWAS) have investigated plasma TG levels.…”

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confidence: 99%

Relationship of lipoprotein lipase gene variants and fasting triglyceride levels in a pediatric population: TheCASPIAN-III study

Kelishadi¹,

Hashemipour²,

Esteki³

et al. 2017

Adv Clin Exp Med

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Lipoprotein lipase and atherosclerosis

Cited by 10 publications

References 30 publications

Lipoprotein Lipase Up‐regulation in Hepatic Stellate Cells Exacerbates Liver Fibrosis in Nonalcoholic Steatohepatitis in Mice

Lipoprotein Lipase Up‐regulation in Hepatic Stellate Cells Exacerbates Liver Fibrosis in Nonalcoholic Steatohepatitis in Mice

A new enzyme-linked immunosorbent assay system for human serum hepatic triglyceride lipase

Relationship of lipoprotein lipase gene variants and fasting triglyceride levels in a pediatric population: TheCASPIAN-III study

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