Transient hypertriglyceridemia: a common finding during Epstein-Barr virus-induced infectious mononucleosis.

BACKGROUND: Hypertriglyceridemia can occur in lymphoproliferative disorders. Infectious mononucleosis is a self-limiting, benign lymphoproliferative disorder. This study aimed to investigate the serum triglyceride concentrations and their change over time in patients with infectious mononucleosis. METHODS: We evaluated an adult patient with severe hypertriglyceridemia (>1000 mg/dL) during infectious mononucleosis and reviewed the records of 360 patients admitted to our hospital because of infectious mononucleosis (median age, 19 years; range, 15-87 years; 51.4% male). We compared the serum triglyceride concentrations with those of a control sample from the general population (n=75). A second triglyceride measurement, obtained during convalescence (median of 30 days after the initial determination), was available for 160 patients. RESULTS: The triglyceride concentrations in the acute phase (median: 156 mg/dL) were significantly higher than those of the controls (median, 76 mg/dL; P<0.001). A total of 194 (53.9%) patients presented with hypertriglyceridemia (>150 mg/dL), which was more common in the patients older than 30 years than in the younger patients (78.6% vs. 50.6%; P<0.001). A significant correlation (P<0.005) was observed between the triglyceride levels and white blood cell counts, total cholesterol levels, and liver damage markers. The triglyceride concentrations decreased during convalescence (P<0.001) and were lower than the initial measurement in 83.7% of the cases. Conversely, the total cholesterol concentrations during the acute phase were lower than those of the controls and increased during convalescence (P<0.001). CONCLUSIONS: Patients with severe infectious mononucleosis frequently show mild, transient hypertriglyceridemia. Further studies are needed to elucidate the mechanisms underlying this finding.

Hexosaminidase A (HEXA) regulates hepatic sphingolipid and lipoprotein metabolism in mice.

Hexosaminidase A (HexA), a heterodimer consisting of HEXA and HEXB, converts the ganglioside sphingolipid GM2 to GM3 by removing a terminal N-acetyl-d-galactosamine. HexA enzyme deficiency in humans leads to GM2 accumulation in cells, particularly in neurons, and is associated with neurodegeneration. While HexA and sphingolipid metabolism have been extensively investigated in the context of neuronal lipid metabolism, little is known about the metabolic impact of HexA and ganglioside degradation in other tissues. Here, we focussed on the role of HexA in the liver, which is a major regulator of systemic lipid metabolism. We find that hepatic Hexa expression is induced by lipid availability and increased in the presence of hepatic steatosis, which is associated with increased hepatic GM3 content. To assess the impact of HEXA on hepatic lipid metabolism, we used an adeno-associated virus to overexpress HEXA in the livers of high-fat diet fed mice. HEXA overexpression was associated with increased hepatic GM3 content and increased expression of enzymes involved in the degradation of glycated sphingolipids, ultimately driving sphingomyelin accumulation in the liver. In addition, HEXA overexpression led to substantial proteome remodeling in cell surface lipid rafts, which was associated with increased VLDL processing and secretion, hypertriglyceridemia and ectopic lipid accumulation in peripheral tissues. This study established an important role of HEXA in modulating hepatic sphingolipid and lipoprotein metabolism.

Case study of hypertriglyceridemia from COVID-19 Pfizer-BioNTech vaccination in a patient with familial hypercholesteremia.

The Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine is the first novel nucleoside-modified messenger ribonucleic acid (modRNA) vaccine to receive Emergency Use Authorization from the Food and Drug Administration in the United States. It is indicated to be used in patients ≥12 years-of-age as of May 25th, 2021, including populations with high atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the potential impact this vaccine may have on serum lipoprotein levels in patients with familial hypercholesteremia (FH), who are predisposed to high ASCVD burden due to elevated low-density lipoprotein cholesterol (LDL-C). We present an interesting case where a patient with heterozygous FH (HeFH) and elevated triglycerides (TG)-controlled for years on medication and apheresis-experienced significantly elevated TG, one day after receiving his second Pfizer-BioNTech COVID-19 vaccine dose. It is not known whether this adverse event may be seen in other FH patients and may be worth assessing in such patients to determine the possibility of a rare adverse reaction from a COVID-19 vaccine.

Differing Nutrient Intake and Dietary Patterns According to the Presence of Hyper-Low-Density Lipoprotein Cholesterolemia or Hypertriglyceridemia.

Dietary choices may have differing effects on low-density lipoprotein cholesterol or triglyceride levels. The aim of this study was to investigate daily nutrient intake and dietary patterns of individuals with hyper-low-density lipoprotein cholesterolemia (hLDL) and hypertriglyceridemia (hTG) in a large Korean population-based study using propensity score (PS) matching. This study used data from the Korea National Health and Nutrition Examination Survey. Propensity score values for the predicted probability of patients with hLDL or hTG were estimated using logistic regression analysis, with age, sex, body mass index, alcohol consumption, smoking status, physical activity status, hypertension, and diabetes. After PS matching, intake of carbohydrates (%) was significantly lower (p = 0.021), and intake of fats (%) and saturated fatty acids (%) was significantly higher in the hLDL group than in the non-hLDL group (p = 0.025 and p = 0.013, respectively). The percentage of individuals with a high score for the Korean Healthy Eating Index (KHEI) "whole grains" or "saturated fatty acids" components was higher in the non-hLDL group than in the hLDL group (p < 0.05 for both). Dietary sodium/potassium ratio was significantly higher in the hTG than in the non-hTG (p = 0.049). Our results suggest that individualized dietary information and counseling require consideration of a person's specific lipid levels.

A case of tamoxifen-induced hypertriglyceridemia monitoring the changes in lipoprotein fractions over time.

BACKGROUND: Tamoxifen, which is one of the selective estrogen receptor modulators (SERMs), can bring out life-threatening complication, e.g. hypertriglyceridemia-induced acute pancreatitis, although it is rare. We precisely report changes in lipoprotein metabolism before and after tamoxifen discontinuation because there have been few reports of it. CASE PRESENTATION: 47-year-old premenopausal woman with dyslipidemia, type 2 diabetes, nonalcoholic fatty liver disease and chronic kidney disease was prescribed tamoxifen as adjuvant therapy after operation of breast cancer. She experienced severe tamoxifen-induced hypertriglyceridemia several months after dosing tamoxifen. Before cessation of tamoxifen, lipoprotein fraction test revealed marked stagnation of VLDL and IDL metabolisms, resulting in severe hypertriglyceridemia (serum triglyceride level was 1881 mg/dL). Seven days after tamoxifen withdrawal, lipoprotein fraction test showed that the metabolisms of endogenous lipoproteins were changed drastically. CONCLUSIONS: From these results, we confirmed that tamoxifen certainly changes lipoprotein metabolism through suppression of post-heparin lipolytic activity. It is very important to evaluate the balance between benefit and risk before dosing tamoxifen and survey lipid profiles constantly during treatment to avoid life-threatening complication when prescription of tamoxifen is planned.

Evaluating the appropriate oral lipid tolerance test model for investigating plasma triglyceride elevation in mice.

The oral lipid tolerance test (OLTT) has been known to assess intestinal fat metabolism and whole-body lipid metabolism, but rodent models for OLTT are not yet established. Differences in OLTT methodology preclude the generation of definitive results, which may cause some confusion about the anti-hypertriglyceridemia effects of the test materials. To standardize and generate more appropriate methodology for the OLTT, we examined the effects of mice strain, dietary lipid sources, fasting period, and gender on lipid-induced hypertriglyceridemia in mice. First, lipid-induced hypertriglyceridemia was more strongly observed in male ddY mice than in C57BL/6N or ICR mice. Second, the administration of olive and soybean oils remarkably represented lipid-induced hypertriglyceridemia. Third, fasting period before the OLTT largely affected the plasma triglyceride elevation. Fasting for 12 h, but less than 48 h, provoked lipid-induced hypertriglyceridemia. Fourth, we explored the suppressive effects of epigallocatechin gallate (EGCG), a green tea polyphenol, on lipid-induced hypertriglyceridemia. The administration of 100 mg/kg of EGCG suppressed lipid-induced hypertriglyceridemia and intestinal lipase activity. Fifth, EGCG-induced suppressive effects were observed after lipid-induced hypertriglyceridemia was observed in male mice, but not in female mice. Lastly, lipid-induced hypertriglyceridemia could be more effectively induced in mice fed a high-fat diet for 1 week before the OLTT. These findings indicate that male ddY mice after 12 h fasting displayed marked lipid-induced hypertriglyceridemia in response to soybean oil. Hence, the defined experiment condition may be a more appropriate OLTT model for evaluating lipid-induced hypertriglyceridemia.

High manganese exposure decreased the risk of high triglycerides in workers: a cross-sectional study.

BACKGROUND: Manganese (Mn) participates in lipid metabolism. However, the associations between Mn exposure and dyslipidaemia is unclear. METHODS: This was a cross-sectional study. Data were collected from the 2017 the Mn-exposed workers healthy cohort (MEWHC). Finally, 803 occupationally Mn-exposed workers included in the study. The workers were divided into two groups. The grouping of this study was based on Mn-Time Weighted Averages (Mn-TWA). The high-exposure group included participants with Mn-TWA greater than 0.15 mg/m3. The low-exposure group included participants with Mn-TWA less than or equal to 0.15 mg/m3. Mn-TWA levels and dyslipidaemia were assessed. RESULTS: After adjustment for seniority, sex, cigarette consumption, alcohol consumption, high-fat diet frequency, medicine intake in the past two weeks, egg intake frequency, drinking tea, WHR, and hypertension, Mn-TWA levels was negatively correlated with high triglycerides (TG) risk in workers overall (OR = 0.51; 95% CI: 0.36, 0.73; p <  0.01). The results of males and females were consistent (OR = 0.53; 95% CI: 0.34, 0.81; p <  0.01) and (OR = 0.47; 95% CI: 0.24, 0.94; p <  0.01), respectively. By performing interactions analyses of workers overall, we observed no significant interactions among confounders. Mn-TWA levels and pack-years on high TG risk (relative excess risk for the interactions (RERI = 2.29, 95% CI: - 2.07, 6.66), (RERI) = 2.98, 95% CI: - 2.30, 8.26). Similarly, smoking status, drinking status, high-fat diet frequency, and Waist-to-Hip Ratio (WHR) showed non-significant interactions with Mn-TWA levels on high TG risk. CONCLUSIONS: This research indicates that high Mn exposure was negatively related to high TG risk in workers.

Integrin ß3 Deficiency Results in Hypertriglyceridemia via Disrupting LPL (Lipoprotein Lipase) Secretion.

OBJECTIVE: Integrin ß3 is implicated in numerous biological processes such as its relevance to blood triglyceride, yet whether ß3 deficiency affects this metabolic process remains unknown. Approach and Results: We showed that the Chinese patients with ß3-deficient Glanzmann thrombasthenia had a 2-fold higher serum triglyceride level together with a lower serum LPL (lipoprotein lipase) level than those with an αIIb deficiency or healthy subjects. The ß3 knockout mice recapitulated these phenotypic features. The elevated plasma triglyceride level was due to impaired LPL-mediated triglyceride clearance caused by a disrupted LPL secretion. Further analysis revealed that ß3 directly bound LPL via a juxtamembrane TIH (threonine isoleucine histidine)720-722 motif in its cytoplasmic domain and functioned as an adaptor protein by interacting with LPL and PKD (protein kinase D) to form the PKD/ß3/LPL complex that is required for ß3-mediated LPL secretion. Furthermore, the impaired triglyceride clearance in ß3 knockout mice could be corrected by adeno-associated virus serotype 9 (AAV9)-mediated delivery of wild-type but not TIH720-722-mutated ß3 genes. CONCLUSIONS: This study reveals a hypertriglyceridemia in both ß3-deficient Chinese patients and mice and provides novel insights into the molecular mechanisms of the significant roles of ß3 in LPL secretion and triglyceride metabolism, drawing attention to the metabolic consequences in patients with ß3-deficient Glanzmann thrombasthenia.

Potentially modifiable blood triglyceride levels by the control of conventional risk factors.

BACKGROUNDS: Triglyceride (TG) is known to be regulated by multiple lifestyle factors rather than genetic factors. This cross-sectional and community-based study (Healthy Twin study in Korea) aimed to estimate the "modifiable TG level" by identifying non-genetic risk factors of TG. METHODS: Participants were recruited between 2006 and 2011 who fulfilled health examinations and detail surveys: 3079 Korean adults including 949 monozygotic twins and 222 dizygotic twins. In order to investigate conventional risk factors, a mixed model accounting for family as a random effect was performed. In addition, we conducted a co-twin control analysis for 452 monozygotic twin (MZ) pairs, to examine non-genetic risk factors and potentially modifiable serum triglyceride levels. RESULTS: After excluding patients on dyslipidemia or diabetes medication, 2672 individuals (1029 men, with mean age of 43.9; and 1643 women with mean age of 43.3; 949 MZ pairs, 222 dizygotic twin pairs, and 1501sibling pairs) were analyzed. Fasting blood sugar (FBS), lipid panel, height, weight, waist (WC) and hip circumference, body mass index (BMI), amount of dietary intake and amount of physical activity was examined after adjusting for age and sex. For conventional analysis, WC, fat %, and BMI were identified as significant factors influencing serum triglyceride levels. Examination of non-genetic factors from the Co-twin control study revealed BMI (beta coefficient 9.94 with C.I. 3.42 to 16.46) and amount of alcohol intake (beta coefficient 0.08 with C.I. 0.02 to 0.14) as significant factors. CONCLUSION: Our findings suggest that controlling body weight and alcohol intake might be effective to control TG; moderate weight control (BMI 1 reduction) and reducing alcohol consumption by 50 g/week (about two glassed of beer) might reduce TG level by 9.94 and 4.0 mg/dL.

Macrophage activation syndrome, a rare complication of primary Sjögren's syndrome: a case report.

BACKGROUND: The association of macrophage activation syndrome and primary Sjögren's syndrome has been rarely reported in the literature. We report the first observation of this association in Africa, south of the Sahara, and we discuss the diagnosis and therapeutic challenge. CASE PRESENTATION: A 26-year-old Mauritanian and Berber woman was followed for primary Sjögren's syndrome. After a voluntary cessation of her usual background treatment, she was admitted to our department for an outbreak of her illness. A clinical examination revealed anemic syndrome, peripheral polyarthritis, coughing rales at both pulmonary bases, and fever at 39.5 °C. On biologic examination, there was bicytopenia with anemia at 5.70 g/dl, lymphopenia at 796/mm3, a biological inflammatory syndrome with a sedimentation rate at 137 mm in the first hour, C-reactive protein at 97 mg/l, hyperferritinemia at 1778 mg/l (9 normal value), and hypergammaglobulinemia at 20.7 g/l of polyclonal appearance. The triglycerides were 1.95 g/l (1.4 normal value) and the lactate dehydrogenase level was 491 IU/l (1.5 normal value). Cytological examination of a medullary puncture revealed an image of hemophagocytosis. An infectious screening was negative. Thoracic computed tomography showed non-specific interstitial lung disease. A diagnosis of macrophage activation syndrome complicating primary Sjögren's syndrome was selected with a probability of 97.2%, according to H-Score. The evolution was favorable under a treatment including etoposide (VP-16). CONCLUSION: Macrophage activation syndrome is a rare entity, rarely reported during primary Sjögren's syndrome. Its spontaneous evolution is invariably fatal. There is no consensus on therapeutic treatment. Etoposide is a therapeutic option especially in forms refractory to corticosteroid therapy.

Associations between dietary patterns and metabolic syndrome in adolescents / Asociación entre patrones de alimentación y síndrome metabólico en adolescentes

Abstract: Objective: Evaluate association of dietary patterns with metabolic syndrome (MetS) and metabolic markers. Materials and methods: 654 adolescents from Guadalajara, Jalisco, participated in a cross-sectional study. Diet was evaluated using a food frequency questionnaire; 24 food groups were integrated, and dietary patterns were derived using cluster analysis. MetS was defined according to International Diabetes Federation (IDF), Cook and colleagues, Ford and colleagues, and de Ferranti and colleagues criteria. Results: Dietary patterns identified were: "DP1", "DP2", and "DP3". Among males, "DP3" was associated with MetS (Cook and collaborators) (OR, 12.14; 95%CI, 1.66-89.05), hypertriglyceridemia (OR, 3.89; 95%CI, 1.01-15.07), and insulin resistance (OR, 6.66; 95%CI, 1.12-39.70). "DP2" was associated with abdominal obesity (OR, 5.11; 95%CI, 1.57-16.66). Conclusions: "DP3" entertained a greater risk of MetS, hypertriglyceridemia, and insulin resistance, while "DP2" possessed a greater risk of abdominal obesity among adolescent males.

Resumen: Objetivo: Evaluar la asociación de patrones dietarios (PD) con síndrome metabólico (SM) y marcadores metabólicos. Material y métodos: Estudio transversal con 654 adolescentes. Dieta evaluada con el cuestionario "frecuencia de consumos de alimentos"; se identificaron 24 grupos de alimentos, para obtener PD mediante análisis de conglomerados. SM se definió según los criterios: Federación de Diabetes Internacional (IDF), Cook y colaboradores, Ford y colaboradores y Ferranti y colaboradores. Resultados: Se identificaron tres PD: "PD1", "PD2" y "PD3". En hombres, "PD3" se asoció con SM (Cook y colaboradores) (RM, 12.14; IC95%, 1.66-89.05), hipertrigliceridemia (RM, 3.89; IC95%, 1.01-15.07) y resistencia a insulina (RM, 6.66; IC95%, 1.12-39.70). El patrón "PD2" se asoció con obesidad abdominal (RM, 5.11; IC95%, 1.57-16.66). Conclusiones: El patrón "PD3" aumenta el riesgo de SM, hipertrigliceridemia y resistencia a insulina y el "PD2" el riesgo de obesidad abdominal en adolescentes hombres.

Soluble insulin receptor and metabolic syndrome

The metabolic syndrome describes a group of signs that increase the likelihood for developing type 2 diabetes mellitus, cardiovascular diseases and some types of cancer. The action of insulin depends on its binding to membrane receptors on its target cells. We wonder if blood insulin could travel bound to proteins and if, in the presence of hyperinsulinemia, a soluble insulin receptor might be generated. We used young adult Wistar rats (which have no predisposition to obesity or diabetes), whose drinking water was added 20 % of sugar and that were fed a standard diet ad libitum for two and six months. They were compared with control rats under the same conditions, but that had running water for consumption. At two months, the rats developed central obesity, moderate hypertension, high triglyceride levels, hyperinsulinemia, glucose intolerance and insulin resistance, i.e., metabolic syndrome. Electrophoresis of the rats’ plasma proteins was performed, followed by Western Blot (WB) for insulin and for the outer portion of the insulin receptor. The bands corresponding to insulin and to the receptor external part were at the same molecular weight level, 25-fold higher than that of free insulin. We demonstrated that insulin, both in control animals and in those with hyperinsulinemia, travels bound to the receptor outer portion (ectodomain), which we called soluble insulin receptor, and that is released al higher amounts in response to plasma insulin increase; in rats with metabolic syndrome and hyperinsulinemia, plasma levels are much higher than in controls. Soluble insulin receptor increase in blood might be an early sign of metabolic syndrome.

Eruptive Xanthomas: A Dermatologic Clue to the Diagnosis of an Underlying Metabolic Disorder.

A 32-year-old man presented to the dermatology department with generalized asymptomatic yellowish papules on an erythematous base, arms, thighs, and buttocks. These lesions had appeared in the previous month (Figure 1). Dermoscopy revealed a homogeneous yellow color, corresponding to dermal xanthomatous deposits, with interconnected fine and dotted vessels (Figure 2). The laboratory findings showed extremely high levels of triglycerides (4.842 mg/dL; normal <150), as well as increased total cholesterol (576 mg/dL; normal <200), fasting blood glucose (294 mg/dL), and glycated hemoglobin 12.3% (normal range 4% to 6%). A skin biopsy demonstrated foamy cells, with extracellular lipid between collagen bundles in the dermis (Figure 3).

An ANGPTL4-ceramide-protein kinase Cζ axis mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia in mice.

Chronic or excess glucocorticoid exposure causes lipid disorders such as hypertriglyceridemia and hepatic steatosis. Angptl4 (angiopoietin-like 4), a primary target gene of the glucocorticoid receptor in hepatocytes and adipocytes, is required for hypertriglyceridemia and hepatic steatosis induced by the synthetic glucocorticoid dexamethasone. Angptl4 has also been shown to be required for dexamethasone-induced hepatic ceramide production. Here, we further examined the role of ceramide-mediated signaling in hepatic dyslipidemia caused by chronic glucocorticoid exposure. Using a stable isotope-labeling technique, we found that dexamethasone treatment induced the rate of hepatic de novo lipogenesis and triglyceride synthesis. These dexamethasone responses were compromised in Angptl4-null mice (Angptl4-/-). Treating mice with myriocin, an inhibitor of the rate-controlling enzyme of de novo ceramide synthesis, serine palmitoyltransferase long-chain base subunit 1 (SPTLC1)/SPTLC2, decreased dexamethasone-induced plasma and liver triglyceride levels in WT but not Angptl4-/- mice. We noted similar results in mice infected with adeno-associated virus-expressing small hairpin RNAs targeting Sptlc2. Protein phosphatase 2 phosphatase activator (PP2A) and protein kinase Cζ (PKCζ) are two known downstream effectors of ceramides. We found here that mice treated with an inhibitor of PKCζ, 2-acetyl-1,3-cyclopentanedione (ACPD), had lower levels of dexamethasone-induced triglyceride accumulation in plasma and liver. However, small hairpin RNA-mediated targeting of the catalytic PP2A subunit (Ppp2ca) had no effect on dexamethasone responses on plasma and liver triglyceride levels. Overall, our results indicate that chronic dexamethasone treatment induces an ANGPTL4-ceramide-PKCζ axis that activates hepatic de novo lipogenesis and triglyceride synthesis, resulting in lipid disorders.

Acquired partial lipodystrophy with metabolic disease in children following hematopoietic stem cell transplantation: a report of two cases and a review of the literature.

Hematopoietic stem cell transplantation (HSCT) has been newly identified as an etiology underlying acquired lipodystrophy (ALD). We report about two children with leukemia who underwent HSCT and later manifested aberrant fat distributions consistent with acquired partial lipodystrophy (APL). Both patients manifested graft-versus-host disease (GVHD), suggesting that GVHD may trigger lipodystrophy. The patients exhibited diabetic blood glucose patterns in the oral glucose tolerance test (OGTT) with high homeostasis model assessment ratios (HOMA-Rs), hypertriglyceridemia, fatty liver, and decreased serum leptin and adiponectin levels. Both patients were diagnosed with APL with metabolic disease. A review of the data of patients with ALD after HSCT revealed common clinical features, including aberrant fat distribution, impaired glucose tolerance (IGT) or diabetes and dyslipidemia. Based on previous reports and our two cases, we speculate that GVHD in the adipose tissue supports the development of ALD after HSCT. In conclusion, children may develop APL after HSCT. Therefore, evaluations of fat distribution and metabolic disease may be important during the long-term follow-up of these patients.

The Chylomicronemia Syndrome Is Most Often Multifactorial: A Narrative Review of Causes and Treatment.

The chylomicronemia syndrome occurs when triglyceride levels are severely elevated (usually >16.95 mmol/L [1500 mg/dL]) and is characterized by such clinical features as abdominal pain, acute pancreatitis, eruptive xanthomas, and lipemia retinalis. It may result from 1 of 3 conditions: the presence of secondary forms of hypertriglyceridemia concurrent with genetic causes of hypertriglyceridemia, termed multifactorial chylomicronemia syndrome (MFCS); a deficiency in the enzyme lipoprotein lipase and some associated proteins, termed familial chylomicronemia syndrome (FCS); or familial partial lipodystrophy. Most chylomicronemia syndrome cases are the result of MFCS; FCS is very rare. In all these conditions, triglyceride-rich lipoproteins accumulate because of impaired plasma clearance. This review describes the 3 major causes of the chylomicronemia syndrome; their consequences; and the approaches to treatment, which differ considerably by group.