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Lipoprotein lipase: new roles for an 'old' enzyme.
Chang, CL
Current opinion in clinical nutrition and metabolic care. 2019;(2):111-115
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Abstract
PURPOSE OF REVIEW Lipoprotein lipase (LpL) is well known for its lipolytic action in blood lipoprotein triglyceride catabolism. This article summarizes the recent mechanistic and molecular studies on elucidating the 'unconventional' roles of LpL in mediating biological events related to immune cell response and lipid transport in the pathogenesis of cardiovascular disease (CVD) and tissue degenerative disorders. RECENT FINDINGS Several approaches to inactivate the inhibitors that block LpL enzymatic activity have reestablished the importance of systemic LpL activity in reducing CVD risk. On the other hand, increasing evidence suggests that focal arterial expression of LpL relates to aortic macrophage levels and inflammatory processes. In the hematopoietic origin, LpL also plays a role in modulating hematopoietic stem cell proliferation and circulating blood cell levels and phenotypes. Finally, building upon the strong genetic evidence on the association with assorted brain disorders, a new era in exploring the mechanistic insights into the functions and activity of LpL in brain that impacts central nerve systems has begun. SUMMARY A better understanding of the molecular action of LpL will help to devise novel strategies for intervention of a number of diseases, including blood cell or metabolic disorders, as well to inhibit pathways related to CVD and tissue degenerative processes.
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Lipolysis of triglyceride-rich lipoproteins, vascular inflammation, and atherosclerosis.
Schwartz, EA, Reaven, PD
Biochimica et biophysica acta. 2012;(5):858-66
Abstract
Epidemiological and interventional studies have implicated elevated triglyceride-rich lipoprotein (TGRL) levels as a risk factor for cardiovascular disease and vascular inflammation, though the results have not been entirely consistent. This appears particularly relevant in model systems where the lipolysis occurs in the setting of established inflammation (e.g., in pre-existing atherosclerotic plaques), rather than in the tissue capillary beds where lipolysis normally occurs. Two main mechanisms seem to link TGRL lipolysis to vascular inflammation. First, lipolysis of TGRL leaves behind partially lipolyzed remnant particles which are better able to enter the vessel wall than nascent TGRL, have a rate of egress substantially lower than their rate of entry, and contain 5-20 times more cholesterol per particle than LDL. Furthermore, remnants do not require oxidation or other modifications to be phagocytized by macrophages, enhancing foam cell formation. Second, saturated fatty acids and oxidized phospholipids released by lipolysis induce inflammation by activating Toll-like receptors of the innate immune system, via oxidative stress, or by greatly amplifying existing pro-inflammatory signals (caused by subclinical endotoxemia) via mitogen-activated protein kinases. However, n-3 and unbound n-9 unsaturated fatty acids released by lipolysis have anti-inflammatory effects. Thus, the contribution of TGRL lipolysis to inflammation likely depends less on the TGRL concentration than on the balance between pro- and anti-inflammatory factors, and on the setting in which the lipolysis occurs. In the setting of the typical "Western" diet, enriched in saturated and oxidized fatty acids and excessive in size, this balance is likely to be tilted towards increased vascular inflammation and atherosclerosis. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.
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A short-term long-chain triglycerides infusion has no influence on immune function of adult patients undergoing gastrointestinal surgery.
Li, X, Ying, J, Zeng, S, Shen, L, Wan, X, Li, X, Tan, H, Pei, H, Zhou, J, Shen, H
JPEN. Journal of parenteral and enteral nutrition. 2007;(3):167-72
Abstract
BACKGROUND Parenteral nutrition (PN) support containing long-chain triglycerides (LCT) plays a critical supportive role in surgical patients' management. This study aims to investigate the effects of intravenous (IV) LCT emulsion on human immune function in adult patients receiving a gastrointestinal surgical procedure. METHODS Sixty adult patients were randomly assigned either to the LCT treatment group (n = 32) or to the control group (n = 28). After an abdominal operation, the subjects received PN treatment with or without LCT for 5 days. Neutrophil, peripheral blood mononuclear cell (PBMC), lymphocyte and CD4/CD8, serum immunoglobulin A (IgA), IgG, IgM, complement C3 and C4, interleukin (IL)-2, IL-4, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma were measured and statistically analyzed. RESULTS The LCT and control groups did not differ significantly at entry in terms of general features. Except for a significant increase of neutrophil number at 24 hours after the surgery in both groups (p < .01), all parameters representing the patients' immune function had no significant difference between the LCT and the control groups with respect to neutrophil and PBMC count, lymphocyte, CD4/CD8, serum IgA, IgG, IgM, complement C3, C4, IL-2, IL-4, IL-10, IL-12, TNF-alpha, and IFN-gamma (p > .05, respectively) 24 hours before the operation, and 24 hours and 120 hours after the operation. CONCLUSIONS The regimens of LCT administration may have diverse effects on human immune function in different patient populations. However, LCT emulsion at an appropriate dose and infusion speed does not alter human immune function of adult patients undergoing moderate gastrointestinal surgery.
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Postprandial monocyte activation in response to meals with high and low glycemic loads in overweight women.
Motton, DD, Keim, NL, Tenorio, FA, Horn, WF, Rutledge, JC
The American journal of clinical nutrition. 2007;(1):60-5
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Abstract
BACKGROUND Recent data show that atherosclerosis is initiated and perpetuated by inflammatory events. Activation of immune cells such as monocytes initiates inflammation, a key step in atherosclerosis. OBJECTIVE We hypothesize that a high-glycemic load meal activates inflammatory cells, and that this is mediated by elevated circulating triacylglycerol-rich lipoproteins. DESIGN Sixteen women [body mass index (in kg/m2): 25.7-29.6], aged 20-48 y, consumed meals with a high or a low glycemic load in a crossover fashion. Blood samples were collected before and up to 8 h after the meals. Samples were measured for glucose, insulin, triacylglycerols, and circulating cytokines, and expression of tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) was measured by flow cytometry. RESULTS At 3.5 h after the test meals, we observed a significant increase in monocytes expressing TNF-alpha with both high-and low-glycemic load meals. Also, expression of IL-1beta in monocytes tended to increase, but the change was not significant. The glycemic load of the meal did not influence circulating cytokines and had only a minimal effect on postprandial triacylglycerol concentrations despite marked postprandial changes in glycemia and circulating insulin concentrations. CONCLUSIONS In the postprandial state, monocytes can be activated by both high-and low-glycemic load meals. The glycemic load of a single meal did not have a significant effect on the degree of activation of the monocytes in women who displayed only a modest increase in circulating triacylglycerols in response to test meals. Future studies should examine the effect of glycemic load in subjects who have a hyperlipemic response to dietary carbohydrate.
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[Effects of medium and long-chain triglyceride on the immune function of burn patients during early postburn stage].
Yan, H, Huang, XH, Xiao, KJ, Liu, XS, Peng, YZ, Huang, YS, Wang, SL
Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns. 2003;(4):202-5
Abstract
OBJECTIVE To explore the effects of medium and long-chain triglyceride on the immune function of burn patients during early postburn stage and its possible mechanism. METHODS Thirty burn patients with TBSA exceeding 30% were enrolled in this study and were randomly divided into two groups (n = 15 in each group). The patients in F group were supplemented orally with enteral nutrient Fresubin 750MCT containing medium (MCT) and long-chain triglyceride (LCT), and those in N group with Nutrition containing only LCT. All the patients were treated with nutritional support beginning from 24 PBH, continued for 10 days. The changes in plasma levels of IL-2, IL-4, PGE(2) and T lymphocyte transformation rate (LTR) in peripheral blood of patients in the two groups were determined on 1, 4, 7 and 10 postburn days (PBDs). RESULTS The plasma IL-2 level in all time points exhibited no difference in all patients (P > 0.05). The plasma level of PGE(2) on PBD 4 in F group was obviously lower than that in N group (P < 0.01). The plasma level of IL-4 on PBDs 4, 7 and 10 in F group were evidently higher than that in N group (P < 0.01). The T LTR in peripheral blood on PBDs 4 and 7 in F group was much higher than that in N group (P < 0.05 - 0.01). CONCLUSION Enteral nutrient containing MCT/LCT seemed to be superior to that containing only LCT in the improvement of postburn immune function in burn patients.
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Elevated remnant-like particles in heterozygous familial hypercholesterolemia and response to statin therapy.
de Sauvage Nolting, PR, Twickler, MB, Dallinga-Thie, GM, Buirma, RJ, Hutten, BA, Kastelein, JJ, ,
Circulation. 2002;(7):788-92
Abstract
BACKGROUND Remnant lipoproteins (RLP-C) are considered important in atherogenesis. Hence, this study was designed to assess RLP-C levels and the effect of statin therapy in patients with familial hypercholesterolemia (FH). Elevated RLP-C levels have been associated with the presence and progression of atherosclerotic disease, and their presence in FH patients has been proposed but never established in a large cohort, nor has their response to statin therapy been confirmed. METHODS AND RESULTS FH patients were recruited from 36 lipid clinics. After a washout period of 6 weeks, all patients were started on monotherapy with 80 mg of simvastatin for 2 years. RLP-C levels were assessed by an immune-separation assay. In 327 FH patients, RLP-C measurements could be performed before and after treatment. Mean total cholesterol (10.55+/-2.17 mmol/L), mean LDL cholesterol (8.40+/-2.13 mmol/L), and median RLP-C (0.47 mmol/L) levels were all severely elevated at baseline. After treatment, RLP-C levels were reduced by 49% (0.24 mmol/L; P<0.0001). Even patients with normal triglyceride levels had elevated RLP-C levels at baseline, and those with high RLP-C levels were generally characterized by a very atherogenic lipoprotein profile. CONCLUSIONS Baseline RLP-C levels are severely elevated in FH patients and are reduced by simvastatin but do not return to normal. These elevated RLP-C levels could be the consequence of impaired function of the LDL receptor in FH. RLP-C levels in FH contribute to an atherogenic lipoprotein profile and could identify patients who require additional treatment.