Hypolipidemia due to Familial Hypobetalipoproteinemia in Adolescents.

Background/Objective: Individuals with heterozygous familial hypobetalipoproteinemia (h-FHBL) due to loss-of-function mutation in the apolipoprotein B gene are typically asymptomatic with mild liver dysfunction, which is often detected incidentally. About 5% to 10% of those with h-FHBL develop steatohepatitis which occasionally progress to cirrhosis especially in the presence of alcohol use, excess calorie consumption, or liver injury. We report 3 patients with hypobetalipoproteinemia, 2 with confirmed h-FHBL, and 1 with suspected h-FHBL. Case Report: Three asymptomatic adolescents presented with low lipid levels detected on screening laboratory studies. Patient 1, a 13 6/12-year-old male and patient 2, a 15 9/12-year-old female, were siblings. Patient 3 was a 12 6/12-year-old female. All had total cholesterol ranging from 61 to 87 mg/dL, low-density lipoprotein cholesterol 10 to 28 mg/dL, and triglycerides 19 to 36 mg/dL. Aspartate transaminase and alanine transaminase levels were normal in patients 1 and 3 and were elevated in patient 2. Liver ultrasounds of patients 2 and 3 showed hepatic steatosis. Molecular testing identified pathogenic variant of apolipoprotein B gene in patients 1 and 2, c.133C>T(p.Arg.45Ter) confirming the diagnosis of h-FHBL. Discussion: More studies are needed in children with h-FHBL and other forms of hypobetalipoproteinemia to improve awareness of these disorders and to develop guidelines for monitoring and risk reduction in affected patients. Conclusion: Health care providers should be aware that persistent hypolipidemia may indicate h-FHBL, which can be a risk factor for liver dysfunction. Youth with h-FHBL should be counseled about lifestyle modifications and screened for the development of metabolic dysfunction-associated steatotic liver disease.

The study on synthesis and vitro hypolipidemic activity of novel berberine derivatives nitric oxide donors.

Berberine was used as the lead compound in the present study to design and synthesize novel berberine derivatives by splicing bromine bridges of different berberine carbon chain lengths coupled nitric oxide donors, and their lipid lowering activities were assessed in a variety of ways. This experiment synthesized 17 new berberine nitric oxide donor derivatives. Compared with berberine hydrochloride, most of the compounds exhibited certain glycerate inhibitory activity, and compounds 6a, 6b, 6d, 12b and 12d showed higher inhibitory activity than berberine, with 6a, 6b and 6d having significant inhibitory activity. In addition, compound 6a linked to furazolidone nitric oxide donor showed better NO release in experiments; In further mechanistic studies, we screened and got two proteins, PCSK9 and ACLY, and docked two proteins with 17 compounds, and found that most of the compounds bound better with ATP citrate lyase (ACLY), among which there may be a strong interaction between compound 6a and ACLY, and the interaction force was better than the target drug Bempedoic Acid, which meaning that 6a may exert hypolipidemic effects by inhibiting ACLY; moreover, we also found that 6a may had the better performance in gastrointestinal absorption, blood-brain barrier permeability, Egan, Muegge class drug principle model calculation and bioavailability.

The complexes of soybean protein isolate and procyanidin B2 have synergistic hypolipidemic activity at the cellular level by activating the AMPKα pathway.

The alkali method was used to prepare soybean protein isolate (SPI) and procyanidin B2 (PCB2) complexes, and the interaction between SPI and PCB2 was studied using multi-spectroscopic methods. The human hepatoma (HepG2) cell hyperlipidemia model was used to explore whether SPI-PCB2 has the potential for synergistic hypolipidemia. According to the findings, PCB2 was primarily linked to SPI via C-S and C-N bonds, and the addition of PCB2 reduced the α-helix structure content of SPI by 4.1%. At the cellular level, the optimal SPI-PCB2 ratio for lowering blood lipids was 1:1. Compared with the model group, the TG content and TC content in the 1:1 group were reduced by 28.7% and 26.3%, respectively. Western blot analysis revealed that SPI-PCB2 = 1:1 exerted synergistic hypolipidemic activity mainly by activating adenosine monophosphate-activated protein kinase α (AMPKα) phosphorylation, inhibiting 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) and fatty acid synthetase (FAS) protein expression, and upregulating carnitine palmitoyl transferase 1A (CPT1A) protein activity.

Angiopoietin-like 3: An important protein in regulating lipoprotein levels.

ANGPTL3 has emerged as a therapeutic target whose inhibition results in profound reductions of plasma lipids, including atherogenic triglyceride-rich lipoproteins and low-density lipoprotein cholesterol. The identification of ANGPTL3 deficiency as a cause of familial combined hypolipidemia in humans hastened the development of anti-ANGPTL3 therapeutic agents, including evinacumab (a monoclonal antibody inhibiting circulating ANGPTL3), vupanorsen (an antisense oligonucleotide [ASO] targeting hepatic ANGPTL3 mRNA for degradation), and others. Advances have also been made in ANGPTL3 vaccination and gene editing strategies, with the former still in preclinical phases and the latter in preparation for Phase 1 trials. Here, we review the discovery of ANGPTL3 as an important regulator of lipoprotein metabolism, molecular characteristics of the protein, mechanisms by which it regulates plasma lipids, and the clinical development of anti-ANGPTL3 agents. The clinical success of therapies inhibiting ANGPTL3 highlights the importance of this target as a novel approach in treating refractory hypertriglyceridemia and hypercholesterolemia.

Common Bean Seeds Obtained by Plant Water Restriction Ameliorates Obesity-Associated Cardiovascular Risk and Insulin Resistance.

The inclusion of beans in the diet has been recommended for obesity control. However, its beneficial effect varies depending on agroclimatic factors acting during plant development. The antiobesogenic capacity of Dalia bean (DB) seeds obtained by water restriction (WR) during the vegetative or reproductive stage of plant growth (50/100 and 100/50% of soil moisture in vegetative/reproductive stage, respectively), during the whole cycle (50/50), and well-watered plants (100/100) was researched. After phytochemical characterization, harvested beans from each experimental unit were pooled among treatments, based on a multivariate canonical discriminant analysis considering concentration of non-digestible carbohydrates (total, soluble and insoluble dietary fiber and resistant starch), phenolic compounds (total phenols, flavonoids, anthocyanins and condensed tannins) and total saponins, which showed no differences among replicas of each treatment. Obesity was induced in rats (UAZ-2015-36851) with a high fat diet (HFD) for four months. Afterwards, rats were fed with the HFD supplemented with 20% of cooked DB for three months. During treatment, 100/50 beans, improved blood triglycerides, cholesterol, and glucose, and alleviated early insulin resistance (IR) related to inhibition of lipase, α-amylase and -glucosidase activity. After sacrifice, a hypolipidemic capacity and atherogenic risk reduction was observed, especially from the 100/50 treatment, suggesting that intake of DB obtained from WR may prevent IR and dyslipidemia.

The evaluation of serum lipid profile in chronic Hepatitis B patients at a Tertiary Care Centre in Western India: A cross-sectional study.

Introduction: Hepatitis B virus (HBV) is known as a metabolovirus due to its impact on lipid and glucose metabolism in the liver. Previous literature showed a trend of hypolipidemia and reduced risk of metabolic syndrome in hepatitis B surface antigen-positive patients. However, data from the Indian population are lacking. We evaluate the relation of lipid profile with HBV infection and severity of liver disease. Materials and Methods: This was an observational cross-sectional study in which 50 patients with chronic hepatitis B and 43 anthropometrically matched seronegative controls were enrolled. Demographical, clinical, and laboratory data including lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol [TC]) were collected. Seropositive patients were categorized based on prognostic models (model for end-stage liver disease [MELD] and Child-Pugh score) for further analysis. Results: Our study revealed significant low levels of serum TC, HDL, and LDL cholesterol in hepatitis B patients compared to seronegative controls (133.06 vs. 162.39, 35.56 vs. 43.65, and 76.62 vs. 99.95 mg/dl respectively, P < 0.05). The patients with high MELD and Child-Pugh score were associated with hypolipidemia. Significant low levels of LDL and TC were observed in Child-Pugh class C in comparison to class A (94.8 vs. 149.2 and 50.6 vs. 87.9 mg/dl respectively, P < 0.05). Conclusions: A significant reduction in various lipid parameters was seen with chronic hepatitis B. Furthermore, prognostic score (high MELD and Child-Pugh score) were associated with hypolipidemia.

Résumé Introduction: Le virus de l'hépatite B (VHB) est connu comme un métabolovirus en raison de son impact sur le métabolisme des lipides et du glucose dans le foie. Précédent la littérature a montré une tendance à l'hypolipidémie et à une réduction du risque de syndrome métabolique chez les patients positifs à l'antigène de surface de l'hépatite B. Cependant, les données de la population indienne font défaut. Nous évaluons la relation entre le profil lipidique et l'infection par le VHB et la gravité de la maladie hépatique. Matériels et méthodes: Il s'agissait d'une étude transversale observationnelle dans laquelle 50 patients atteints d'hépatite B chronique et 43 des témoins séronégatifs appariés ont été recrutés. Données démographiques, cliniques et de laboratoire, y compris le profil lipidique (lipoprotéines de haute densité [HDL], lipoprotéines de basse densité [LDL], triglycérides et cholestérol total [TC]) ont été collectés. Les patients séropositifs ont été classés en fonction de modèles pronostiques (modèle pour l'hépatopathie terminale [MELD] et score de Child-Pugh) pour une analyse plus approfondie. Résultats: Notre étude a révélé des taux sériques bas significatifs de cholestérol TC, HDL et LDL chez les patients atteints d'hépatite B par rapport aux témoins séronégatifs (133,06 contre 162,39, 35,56 vs 43,65 et 76,62 vs 99,95 mg/dl respectivement, P < 0,05). Les patients avec un MELD et un score de Child-Pugh élevés étaient associés à hypolipidémie. Des niveaux significativement faibles de LDL et de TC ont été observés dans la classe C de Child-Pugh par rapport à la classe A (94,8 vs. 149,2 et 50,6 vs 87,9 mg/dl respectivement, P < 0,05). Conclusions: Une réduction significative de divers paramètres lipidiques a été observée avec l'hépatite chronique B. De plus, le score pronostique (MELD élevé et score de Child-Pugh) était associé à une hypolipidémie. Mots-clés: Cholestérol, maladie hépatique chronique, hépatite B, hypolipidémie, métabolisme lipidique.

Bioactive polysaccharides and their potential health benefits in reducing the risks of atherosclerosis: A review.

Atherosclerosis is a kind of lipid-driven chronic inflammatory disease of arteries and is the principal pathological basis of life-threatening cardiovascular disease events, such as strokes and heart attacks. Clinically, statins are the most commonly prescribed drugs for the treatment of atherosclerosis, but prolonged use of these drugs exhibit many adverse reactions and have limited efficacy. Polysaccharides are important natural biomacromolecules widely existing in plants, animals, microorganisms and algae. They have drawn considerable attention worldwide due to their multiple healthy functions, along with their non-toxic property. Importantly, a growing number of studies have demonstrated that bioactive polysaccharides exhibit prominent efficiency in controlling atherosclerotic risk factors like hyperlipemia, hypertension, oxidative stress, and inflammation. In recent decades, various bioactive polysaccharides with different structural features and anti-atherosclerotic potential from natural sources have been isolated, purified, and characterized. The aim of this review is to focus on the research progress of natural polysaccharides in reducing the risks of atherosclerosis based on evidence of in vitro and in vivo studies from 1966 to 2022. PRACTICAL APPLICATIONS: In the future, it is still necessary to strengthen the research on the development and mechanism of polysaccharides with anti-atherosclerotic potential. These anti-atherosclerotic polysaccharides with different structural characteristics and physiochemical properties from different sources will constitute a huge source of materials for future applications, especially in functional foods and drugs. The information summarized here may serve as useful reference materials for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

Hypoglycemic Effects of Lycium barbarum Polysaccharide in Type 2 Diabetes Mellitus Mice via Modulating Gut Microbiota.

This study aims to explore the molecular mechanisms of Lycium barbarum polysaccharide (LBP) in alleviating type 2 diabetes through intestinal flora modulation. A high-fat diet (HFD) combined with streptozotocin (STZ) was applied to create a diabetic model. The results indicated that LBP effectively alleviated the symptoms of hyperglycemia, hyperlipidemia, and insulin resistance in diabetic mice. A high dosage of LBP exerted better hypoglycemic effects than low and medium dosages. In diabetic mice, LBP significantly boosted the activities of CAT, SOD, and GSH-Px and reduced inflammation. The analysis of 16S rDNA disclosed that LBP notably improved the composition of intestinal flora, increasing the relative abundance of Bacteroides, Ruminococcaceae_UCG-014, Intestinimonas, Mucispirillum, Ruminococcaceae_UCG-009 and decreasing the relative abundance of Allobaculum, Dubosiella, Romboutsia. LBP significantly improved the production of short-chain fatty acids (SCFAs) in diabetic mice, which corresponded to the increase in the beneficial genus. According to Spearman's correlation analysis, Cetobacterium, Streptococcus, Ralstonia. Cetobacterium, Ruminiclostridium, and Bifidobacterium correlated positively with insulin, whereas Cetobacterium, Millionella, Clostridium_sensu_stricto_1, Streptococcus, and Ruminococcaceae_UCG_009 correlated negatively with HOMA-IR, HDL-C, ALT, AST, TC, and lipopolysaccharide (LPS). These findings suggested that the mentioned genus may be beneficial to diabetic mice's hypoglycemia and hypolipidemia. The up-regulation of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and insulin were remarkably reversed by LBP in diabetic mice. The real-time PCR (RT-PCR) analysis illustrated that LBP distinctly regulated the glucose metabolism of diabetic mice by activating the IRS/PI3K/Akt signal pathway. These results indicated that LBP effectively alleviated the hyperglycemia and hyperlipidemia of diabetic mice by modulating intestinal flora.

Optimization of clofibrate with O-desmethyl anetholtrithione lead to a novel hypolipidemia compound with hepatoprotective effect.

Oxidative stress and inflammation were considered to be the major mechanisms in liver damage caused by clofibrate (CF). In order to obtain lipid-lowering drugs with less liver damage, the structure of clofibrate was optimized by O-desmethyl anetholtrithione and got the target compound clofibrate-O-desmethyl anetholtrithione (CF-ATT). CF-ATT significantly reduced the levels of plasma triglycerides (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR-1339. In addition, CF-ATT has a significantly protective effect on the liver compared with CF. The liver weight and liver coefficient were reduced. The hepatic function indexes were also decreased, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Histopathological examination of the liver revealed that inflammatory cell infiltration, nuclear degeneration, cytoplasmic loosening and hepatocyte necrosis were ameliorated by administration with CF-ATT. The hepatoprotective mechanism showed that CF-ATT significantly up-regulated Nrf2 and HO-1 protein expression and down-regulated p-NF-κB P65 expression in the liver. CF-ATT has obviously antioxidant and anti-inflammatory activity. These findings suggested that CF-ATT has significant hypolipidemia activity and exact hepatoprotective effect possibly through the Nrf2/NF-κB-mediated signal pathway.

Reverse Epidemiology for Lipid Disorders in Hemodialysis-Dependent Patients: Role of Dilutional Hypolipidemia.

Introduction: Atherosclerotic cardiovascular disease is a major cause of mortality and morbidity in dialysis patients. Compared to general population, dialysis patients have lower lipid levels and higher vascular events. This paradox is popularly known as reverse epidemiology. Present study is an attempt to understand reasons for low lipids in dialysis patients. Subjects and Methods: This was a prospective observational multicentric study involving three stages across six dialysis units with Care Hospitals, Hyderabad. Maintenance hemodialysis patients were studied with fasting lipid profiles [TC, LDL-c, HDL-c, and TG], pre- and post-dialysis blood lipids and effluent water lipid profiles. Other parameters studied were use of statins, interdialytic weight gain, and ultrafiltration. All patients had uniform dialysis protocols regarding filter used and dialysis duration. Results: Of the 91 patients studied, we observed significant rise in post-dialysis TC, LDL, and HDL [P < 0.01] and lower lipids [P < 0.01] just before the next dialysis. Lipids were least filtered across the membrane except HDL, which was found in effluent water for more than 60% of patients. Single use of dialyser was associated with higher rise in post dialysis lipids as well as HDL getting filtered in effluent [P = 0.24]. Rosuvastatin was associated with lower lipid values [P = 0.08] and BMI [P = 0.19]. Conclusions: Low lipid levels in dialysis patients are due to dilutional hypolipidemia and needs correction with an equation proposed in present study. Corrected lipids should be used for risk stratification and deploying treatment.

Effect of COVID-19 on lipid profile parameters and its correlation with acute phase reactants: A single-center retrospective analysis.

Background and objective: The development and correlation of dyslipidemia is unknown in COVID-19. This investigation was performed to assess the pathological alterations in lipid profile and their association in COVID-19. Methods: This was a retrospective study performed on real-world patients to assess serum levels of LDL-C, HDL, TG, TC on COVID-19 patients (mild: 319; moderate: 391; critical: 357). Age- and gender-matched controls who had their lipid profiles in the same period were included as the control group. Results: LDL-C, HDL, TG, and TC levels were significantly lower in COVID-19 patients when compared with the control group (P < 0.001, 0.047, 0.045, <0.001, respectively). All parameters decreased gradually with COVID-19 disease severity (LDL-C: median (IQR), mild: 98 (91,134); moderate: 97 (81,113); critical: 68 (68,83); HDL: mild: 45 (37,50); moderate: 46 (41,50); critical: 40 (37,46); TG: mild: 186 (150,245); moderate: 156 (109,198); critical: 111 (98,154); TC: mild: 224 (212,238); moderate: 212 (203,213); critical: 154 (125,187)). Logistic regression demonstrated lipid profile as predictor of severity of COVID-19 disease. Conclusion: Hypolipidemia develops in increasing frequency with severe COVID-19 disease. It inversely correlates with levels of acute-phase reactants, indicating SARS-COV-2 as the causative agent for alteration in lipid and thyroid levels.

Effect of Washed Microbiota Transplantation on Patients With Dyslipidemia in South China.

Background and Aims: Although the manual crude fecal microbiota transplantation (FMT) reduces blood lipids in animal models of hyperlipidemia, its clinical effect on blood lipid metabolism in patients with hyperlipidemia and hypolipidemia remains unclear, especially in the Chinese population. It was reported that washed microbiota transplantation (WMT) was safer, more precise, and more quality-controllable than the crude FMT by manual. This study aimed to investigate the feasibility and effectiveness of WMT on lipid metabolism in the Chinese population. Methods: Clinical data of patients with various indications who received WMT for 1-3 treatment procedures were collected. Changes in blood lipids before and after WMT, namely, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), liver fat attenuation, and liver stiffness measurement, were compared. Results: A total of 177 patients (40 cases of hyperlipidemia, 87 cases with normal blood lipids, and 50 cases of hypolipidemia) were enrolled in the First Affiliated Hospital of Guangdong Pharmaceutical University. WMT has a significant therapeutic effect in reducing blood lipid levels (TC and TG) in the short- and medium term in patients with hyperlipidemia (p <0.05). Hyper blood lipid decreased to normal in the short-term (35.14%; p <0.001), and LDL-C changed to normal in the medium term (33.33%; p = 0.013). In the hypolipidemia group, 36.36% and 47.06% changed to normal in the short-term (p = 0.006) and medium term (p = 0.005) of therapeutic effects based on blood lipid levels. In the normal blood lipid group and the low-risk group of atherosclerotic cardiovascular disease (ASCVD), the change was not statistically significant, indicating that WMT does not increase the risk of blood lipid and ASCVD in the long-term. Conclusions: WMT treatment changes blood lipids in patients with hyperlipidemia and hypolipidemia without serious adverse events, with no risk for increasing blood lipids and ASCVD in the long-term. There were significant decreased TC, TG, and LDL-C levels in the medium term of WMT treatment for hyperlipidemia. Therefore, the regulation of gut microbiota by WMT may indicate a new clinical method for the treatment of dyslipidemia.

In vivo anti-lipidemic and antioxidant potential of collagen peptides obtained from great hammerhead shark skin waste.

The aim of the present study was to evaluate the ability of fish collagen peptides (FCP) derived from the skin of great hammerhead shark (Sphyrna mokarran) in attenuating the high fat diet-alcohol induced hyperlipidemia. The oral supplementation of FCP in high fat diet-alcohol fed experimental rats confirmed the regulation of body weight to normal level. The FCP treated group revealed the efficient lipid lowering ability by enhancing the cholesterol metabolism. Western blot analysis of the lipid metabolic enzymes revealed that the oral-intake of FCP has down-regulated the expression levels of fatty acid synthase and 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Simultaneously, the expression levels of Lecithin-cholesterol acyltransferase (LCAT) in liver was up-regulated. Histopathology analysis of liver tissues demonstrated that the FCP treated group maintained normal liver parenchyma with moderate inflammatory infiltration, whereas the statin treated group developed centrilobular fibrosis, atrophy of hepatocytes and moderate inflammatory infiltration. Oral dietary supplementation of FCP enhanced the activity levels of both superoxide dismutase and catalase enzymes and, lowered the levels of lipid peroxidation in liver tissues. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05118-0.

Prognostic Value of Decreased High-Density Lipoprotein Cholesterol Levels in Infective Endocarditis.

(1) Background: Simple parameters to be used as early predictors of prognosis in infective endocarditis (IE) are lacking. The aim of this study was to evaluate the prognostic role of high-density-lipoprotein cholesterol (HDL-C) and also of total-cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and triglycerides, in relation to clinical features and mortality, in IE. (2) Methods: Retrospective analysis of observational data from 127 consecutive patients with a definite diagnosis of IE between 2016 and 2019. Clinical, laboratory and echocardiography data, mortality, and co-morbidities were analyzed in relation to HDL-C and lipid profile. (3) Results: Lower HDL-C levels (p = 0.035) were independently associated with in-hospital mortality. HDL-C levels were also significantly lower in IE patients with embolic events (p = 0.036). Based on ROC curve analysis, a cut-off value was identified for HDL-C equal to 24.5 mg/dL for in-hospital mortality. HDL-C values below this cut-off were associated with higher triglyceride counts (p = 0.008), higher prevalence of S. aureus etiology (p = 0.046) and a higher in-hospital mortality rate (p = 0.004). Kaplan-Meier survival analysis showed higher 90-day mortality in patients with HDL-C ≤ 24.5 mg/dL (p = 0.001). (4) Conclusions: Low HDL-C levels could be used as an easy and low-cost marker of severity in IE, particularly to predict complications, in-hospital and 90-day mortality.

Nostoc flagelliforme capsular polysaccharides from different culture conditions improve hyperlipidemia and regulate intestinal flora in C57BL/6J mice to varying degrees.

Two capsular polysaccharides (WL-CPS-1 and GLU-CPS-1) purified from Nostoc flagelliforme under normal and mixotrophic culture conditions were used to investigate the hypolipidemic activity and effect on intestinal flora in C57BL/6J mice respectively. Their molecular weight and monosaccharide composition have been determined in previous studies. They both improved the lipid level by affecting the expression of lipid metabolism genes. They down-regulated the TNF-α and IL-1ß levels in serum and up-regulated the activity of antioxidant enzymes in liver thus decreased the atherosclerosis index and MDA content. They up-regulated the short chain fatty acids (SCFAs) synthesis. They decreased the abundance of pathogenic bacteria and increased the abundance of probiotics positively correlated with SCFAs. Compared with WL-CPS-1, GLU-CPS-1 exhibited higher in vivo activity and enriched Odoribacter and Alloprevotella correlating with the gene expression of lipid metabolism, suggesting that the bioactivity of polysaccharides could be regulated by culture conditions. These findings contributed to application of N. flagelliforme polysaccharides with higher activity in hypolipidemia by adjusting culture conditions.

Structural simplification and bioisostere principle lead to Bis-benzodioxole-fibrate derivatives as potential hypolipidemic and hepatoprotective agents.

The bis-benzodioxole-fibrate hybrids were designed by structural simplification and bioisostere principle. Lipids lowering activity was preliminarily screened by Triton WR 1339 induced hyperlipidemia mice model, in which T3 showed the best hypolipidemia, decreasing plasma triglyceride (TG) and total cholesterol (TC), which were better than sesamin and fenofibrate (FF). T3 was also found to significantly reduce TG, TC and low density lipoprotein cholesterin (LDL-C) both in plasma and liver tissue of high fat diet (HFD) induced hyperlipidemic mice. In addition, T3 showed hepatoprotective activity, which the noteworthy amelioration in liver aminotransferases (AST and ALT) was evaluated and the histopathological observation exhibited that T3 inhibited lipids accumulation in the hepatic and alleviated liver damage. The expression of PPAR-α receptor involved lipids metabolism in liver tissue significantly increased after T3 supplementation. Other potent activity, such as antioxidation and anti-inflammation, was also observed. The molecular docking study revealed that T3 has good affinity activity toward to the active site of PPAR-α receptor. Based on these findings, T3 may serve as an effective hypolipidemic agent with hepatoprotection.

Time series decomposition into dyslipidemia prevalence among urban Chinese population: secular and seasonal trends.

BACKGROUND: Previous epidemiological studies have indicated the seasonal variability of serum lipid levels. However, little research has explicitly examined the separate secular and seasonal trends of dyslipidemia. The present study aimed to identify secular and seasonal trends for the prevalence of dyslipidemia and the 4 clinical classifications among the urban Chinese population by time series decomposition. METHODS: A total of 306,335 participants with metabolic-related indicators from January 2011 to December 2017 were recruited based on routine health check-up systems. Multivariate direct standardization was used to eliminate uneven distributions of the age, sex, and BMI of participants over time. Seasonal and trend decomposition using LOESS (STL decomposition) was performed to break dyslipidemia prevalence down into trend component, seasonal component and remainder component. RESULTS: A total of 21.52 % of participants were diagnosed with dyslipidemia, and significant differences in dyslipidemia and the 4 clinical classifications were observed by sex (P <0.001). The secular trends of dyslipidemia prevalence fluctuated in 2011-2017 with the lowest point in September 2016. The dyslipidemia prevalence from January to March and May to July was higher than the annual average (λ = 1.00, 1.16, 1.06, 1.01, 1.02, 1.03), with the highest point in February. Different seasonal trends were observed among the 4 clinical classifications. Compared to females, a higher point was observed among males in February, which was similar to participants aged < 55 years (vs. ≥ 55 years) and participants with a BMI ≤ 23.9 (vs. BMI > 23.9). CONCLUSIONS: There were significant secular and seasonal features for dyslipidemia prevalence among the urban Chinese population. Different seasonal trends were found in the 4 clinical classifications of dyslipidemia. Precautionary measures should be implemented to control elevated dyslipidemia prevalence in specific seasons, especially in the winter and during traditional holidays.

Current Diagnosis and Management of Abetalipoproteinemia.

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.

Hypotriglyceridemias/hypolipidemias. / Hipotrigliceridemias/hipolipidemias.

Hypolipoproteinemias are characterized by a decrease in the plasma concentration of lipoproteins. Within them, we find two groups: hypobetalipoproteinemias (HBL), due to a decrease in the plasma concentration of lipoproteins containing apolipoprotein B, and hypoalphalipoproteinemias. Hypolipoproteinemias can be classified according to their origin, into primary and secondary. Primary HBLs are rare entities produced by mutations in different genes. So far, more than 140 mutations have been identified in the APOB, PCSK9, ANGPTL3, MTTP, and SAR1 genes. Early diagnosis and treatment are essential to avoid the development of serious complications. In this review we address the diagnosis and treatment of HBL, especially those in which there is hypotriglyceridemia.

Normal plasma apoB48 despite the virtual absence of apoB100 in a compound heterozygote with novel mutations in the MTTP gene.

"Normotriglyceridemic abetalipoproteinemia (ABL)" was originally described as a clinical entity distinct from either ABL or hypobetalipoproteinemia. Subsequent studies identified mutations in APOB gene which encoded truncated apoB longer than apoB48. Therefore, "Normotriglyceridemic ABL" can be a subtype of homozygous familial hypobetalipoproteinemia. Here, we report an atypical female case of ABL who was initially diagnosed with "normotriglyceridemic ABL", because she had normal plasma apoB48 despite the virtual absence of apoB100 and low plasma TG level. Next generation sequencing revealed that she was a compound heterozygote of two novel MTTP mutations: nonsense (p.Q272X) and missense (p.G709R). We speculate that p.G709R might confer residual triglyceride transfer activity of MTTP preferentially in the intestinal epithelium to the hepatocytes, allowing production of apoB48. Together, "normotriglyceridemic ABL" may be a heterogenous disorder which is caused by specific mutations in either APOB or MTTP gene.