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Background Drug-induced liver injury (DILI) is the leading cause of acute liver failure in the United States. DILI is mainly caused by painkillers and fever reducers, and it is often characterized by the type of hepatic injury (hepatocellular or cholestatic). This report presents a case of fenofibrate-induced severe jaundice in a 65-year-old Korean male with no prior history of liver disease. We offer a strategy for patients who present signs of severe liver injury with jaundice and high elevations in serum transaminases. Case summary A 65-year-old male visited the gastroenterology outpatient clinic of a tertiary hospital due to increased levels of liver enzyme and total bilirubin which were incidentally detected through a preoperative screening test. Abdominal ultrasound and computed tomography showed no biliary obstruction or non-specific findings in the liver. Liver biopsy was performed and the patient was finally diagnosed with acute cholestatic hepatitis. Following the biopsy, steroid therapy was initiated and after 3 wk of treatment, the total bilirubin level was reduced to 7.22 mg/dL. Conclusion In patients with hyperlipidemia, treatment including fenofibric acid induces rare complications such as severe jaundice and acute cholestatic hepatitis, warranting clinical attention.

Severe hypertriglyceridemia (HTG) (>885 mg/dL) can be caused by familial partial lipodystrophy type 3 (FPLD3), an autosomal dominant disorder caused by loss of function of the peroxisome proliferator-activated receptor gamma (PPARG), characterized by abnormal distribution of fat and metabolic derangements. This case reports a 16-year-old female (body mass index, 23.5 kg/m2) hospitalized twice for pancreatitis (triglycerides [TG] level >2,200 mg/dL). Her treatment management included bowel rest, insulin infusion, and plasmapheresis. A low-fat diet with 10 g of fat daily and 160 mg of fenofibrate daily decreased fasting TG to 411 mg/dL (range, 0–149 mg/dL). The patient had a normal leptin level. Panel testing of genes that impact TG metabolism revealed a known pathogenic variant in the PPARG gene (c.452A>G p.Tyr151Cys). A second variant detected in this gene, c.1003G>C (p.Val335Leu), is considered benign. Her glycosylated hemoglobin of 6.6% and 2-hour oral glucose tolerance test confirmed type 2 diabetes mellitus (T2DM). This study reports the earliest detection of T2DM in an adolescent with a pathogenic variant of PPARG. PPARG-related FPLD3 should be considered in lean children that present with severe HTG and insulin resistance, and subsequent treatment with proliferator-activated receptor gamma agonists, specifically thiazolidinediones, should be considered.

PURPOSE Residual cardiovascular risk reduction by fenofibrate in patients with high serum triglyceride (TG) levels despite previous statin monotherapy is not well characterized. The purpose of this study was to evaluate the efficacy and safety of a combination of choline fenofibrate and statin in patients with inadequately controlled TG levels despite previous statin monotherapy. METHODS This prospective, multicenter, randomized, double-blind study was conducted in Korea. A total of 133 patients with controlled LDL-C but elevated TG levels, already receiving statin monotherapy, were enrolled in the study, which was conducted from July 2018 to December 2019. Patients were randomly assigned to receive combination therapy with choline fenofibrate and statin or statin monotherapy in a 1:1 ratio. After 8 weeks of treatment, the lipid profiles and safety parameters of the patients in the 2 groups were compared. FINDINGS The study included 127 patients (64 in the combination group and 63 in the control group) older than 19 years. After 8 weeks of therapy, mean serum TG levels significantly decreased from 269.8 to 145.5 mg/dL (P < 0.0001) in the combination therapy group, whereas no significant changes occurred in the statin monotherapy group (from 271.1 to 280.5 mg/dL). Contrarily, the mean serum HDLC levels significantly increased from 45.0 to 50.4 mg/dL (P = 0.0004) in the combination therapy group, whereas there were no significant changes in the monotherapy group (from 44.3 to 44.7 mg/dL). There were no additional serious adverse events in the combination therapy group compared with the statin monotherapy group. IMPLICATIONS The combination therapy using choline fenofibrate and statin was found to be effective in serum TG control and likely tolerable in patients with high TG levels despite statin monotherapy. A larger study, conducted for a longer duration, is needed to evaluate the effectiveness of this combination in reducing cardiovascular risk. ClinicalTrials.gov identifier: NCT03874260.

Maternally inherited diabetes and deafness is a rare genetic disease mainly caused by a point mutation in mitochondrial deoxyribonucleic acid. Lipoprotein lipase gene mutations are associated with familial dyslipidemias, which are difficult to manage. We reported for the first time a case that had both maternally inherited diabetes and severe hyperlipidemia caused by lipoprotein lipase gene mutation (C.347(exon3)G>C) that was resistant to fenofibrate and atorvastatin. We were able to manage the patient’s hyperlipidemia with bezafibrate, and her diabetes was well controlled with insulin. In conclusion, genetic testing is helpful in identifying rare and interesting cases when clinicians suspect inheritable diseases. Additionally, when one fibrate drug is ineffective in treating hyperlipidemia, it might be worthwhile trying another fibrate.

Accumulation of cytotoxic bile acids (BAs) during cholestasis can result in liver failure. Glucuronidation, a phase II metabolism pathway responsible for BA detoxification, is regulated by peroxisome proliferator–activated receptor alpha (PPARα). This study investigates the efficacy of adjunct fenofibrate therapy to up‐regulate BA‐glucuronidation and reduce serum BA toxicity during cholestasis. Adult patients with primary biliary cholangitis (PBC, n = 32) and primary sclerosing cholangitis (PSC, n = 23), who experienced an incomplete response while receiving ursodiol monotherapy (13‐15 mg/kg/day), defined as serum alkaline phosphatase (ALP) ≥ 1.5 times the upper limit of normal, received additional fenofibrate (145‐160 mg/day) as standard of care. Serum BA and BA‐glucuronide concentrations were measured by liquid chromatography–mass spectrometry. Combination therapy with fenofibrate significantly decreased elevated serum ALP (−76%, P, Combination therapy with fenofibrate favorably alters BA‐glucuronidation as a PPARa‐mediated mechanism to reduce elevated serum BAs in patients with PBC and PSC who are incomplete responders to Ursodiol monotherapy. This study also identifies serum BA‐glucuronides and their respective metabolic ratios as indicators of response to therapy. Serum BA‐glucuronides may serve as mechanistically relevant secondary endpoints in clinical trials for PBC and PSC with anti‐cholestatic agents.

In this study, we hypothesized that deregulation in the maintenance of the pool of coenzyme A (CoA) may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Specific deletion of Acot12 (Acot12−/−), the major acyl-CoA thioesterase, induced the accumulation of acetyl-CoA and resulted in the stimulation of de novo lipogenesis (DNL) and cholesterol biosynthesis in the liver. KEGG pathway analysis suggested PPARα signaling as the most significantly enriched pathway in Acot12−/− livers. Surprisingly, the exposure of Acot12−/− hepatocytes to fenofibrate significantly increased the accumulation of acetyl-CoA and resulted in the stimulation of cholesterol biosynthesis and DNL. Interaction analysis, including proximity-dependent biotin identification (BioID) analysis, suggested that ACOT12 may directly interact with vacuolar protein sorting-associated protein 33A (VPS33A) and play a role in vesicle-mediated cholesterol trafficking and the process of lysosomal degradation of cholesterol in hepatocytes. In summary, in this study, we found that ACOT12 deficiency is responsible for the pathogenesis of NAFLD through the accumulation of acetyl-CoA and the stimulation of DNL and cholesterol via activation of PPARα and inhibition of cholesterol trafficking., Non-alcoholic fatty liver disease: Boosting regulatory enzyme a potential treatment A deficiency in levels of a key enzyme disturbs lipid metabolism in the liver and triggers non-alcoholic fatty liver disease (NAFLD). NAFLD is a common chronic condition in which fat builds up in the liver, heightening the risk of serious health problems. However, the exact mechanisms behind NAFLD are unclear. In experiments on mice, Eun-Jung Jin at Wongwang University in Iksan, South Korea, and co-workers found that deficiencies of an enzyme called ACOT12 can induce NAFLD regardless of dietary intake. The team generated mice without the Acot12 gene, which boosted the biosynthesis of lipid and accumulation of cholesterol in liver cells. Further examination showed that ACOT12 may directly interact with a protein that prompts cholesterol trafficking and degradation. Loss of ACOT12 activated a signaling pathway that inhibited this process. Their findings may inform NAFLD therapies.

BackgroundSafe, effective, and readily available drug therapies are required for the management of hyperlipidemia and its associated complications in dogs.ObjectivesTo investigate the efficacy of a micronized, nanocrystal formulation of fenofibrate (Tricor) in the treatment of hyperlipidemia in dogs.AnimalsTen client-owned dogs with primary (n=7) and secondary (n=3) hyperlipidemia. All dogs had hypertriglyceridemia at baseline; 3 dogs also had hypercholesterolemia.MethodsProspective dose-escalation study. Dogs were treated with fenofibrate orally once daily in up to 3cycles of 21 days each. Fenofibrate dose was increased at the end of each cycle if hypertriglyceridemia persisted and adverse effects were not documented. Complete blood count, biochemistry, and urine protein:creatinine ratio were collected serially. Baseline (T0) parameters were compared to time of maximal reduction in serum triglyceride concentrations (T1) and reported as median (range).ResultsTriglycerides normalized in all dogs (T0=662 mg/dL [189-2391]; T1= 113 mg/dL [81-132]; P=.002). Fenofibrate dose at T1=6.4mg/kg PO q24h (range, 2.2-13.5). T1 was achieved at 3 (n=4), 6 (n=4), and 9 (n=2) weeks. Serum cholesterol concentrations decreased in 9 of 10 dogs. Quiet demeanor and firm stools in 1 dog were the only reported adverse reactions. Fenofibrate administration resulted in a significant reduction in median alkaline phosphatase activity (P=.049).Conclusions and clinical importanceOver 21 to 63 days, TriCor was effective in the management of primary and secondary hyperlipidemia in dogs.

BACKGROUND This meta-analysis aimed to evaluate the effectiveness of fibrates in the treatment of pruritus in patients with primary biliary cholangitis (PBC), so as to guide the clinical treatment of such cases. METHODS Searches of the PubMed, Google Scholar, and Cochrane Library databases were performed to identify randomized controlled trials (RCTs) and prospective studies published up to December 2020 that used bezafibrate and fenofibrate as treatments for pruritus in patients with PBC. Data extraction and quality evaluation of the included literature were performed. Review Manager 5.3 software was employed for statistical analysis of the data. RESULTS This meta-analysis included 7 studies, comprising 382 patients with PBC, which assessed the efficacy of bezafibrate and fenofibrate for treating pruritus. The results showed that treatment with fibrates significantly improved pruritus symptoms in patients with PBC [relative risk (RR) =6.52, 95% confidence interval (CI): 3.26-13.06, P

Introduction: Hyperbilirubinemia is a common problem in the neonatal period. Phototherapy is the most important proposed treatments for hyperbilirubinemia, but several drugs along with phototherapy are used with recent advances. Aim: To see the effect of oral fenofibrate on serum bilirubin level in term neonates with unconjugated hyperbilirubinaemia. Methods: This prospective study was carried out in Combined Military Hospital Cumilla from July 2018 to June 2019. Total 60 term and normal birth weight neonates with neonatal jaundice were enrolled in this study. Jaundiced newborns presenting with infection, G6PD deficiency, conjugated bilirubin >2 mg/dl or >15% of total serum bilirubin (TSB) and congenital anomalies were excluded from this study. These neonates were randomly allocated to the Fenofibrate group (30 cases) and Control group (30 cases). Total serum bilirubin was measured every 24 hours till the end of phototherapy and at the time of discharge. Statistical analysis was done using SPSS 22.0 and p

Dysbetalipoproteinaemia (or type III hyperlipoproteinaemia) is a severe mixed hyperlipidaemia resulting from the accumulation of remnant chylomicron and VLDL particles in plasma, also called β-VLDL. It is caused by a defect in the recognition by hepatic LDL and lipoprotein receptor-related protein (LRP) of β-VLDL. Mutations in the APOE gene, especially in subjects homozygous for the ɛ2/ɛ2 allele, are responsible for this lack of receptor recognition. Dysbetalipoproteinaemia represents 2-5% of the mixed dyslipidaemias seen in Lipid Units, is highly atherogenic and predisposes to diffuse atheromatosis, either coronary, peripheral vascular, or carotid, so early diagnosis and treatment is necessary. The presence of hypertriglyceridaemia, with non-HDL cholesterol/apolipoprotein B ratios>1.43 (in mg/dL) followed by APOE genotyping is the method of choice in the diagnosis of dysbetalipoproteinaemia. It is a dyslipidaemia that responds well to hygienic-dietary treatment, although the combination of statin and fenofibrate is often necessary to achieve optimal control.

The aims of the present study were to investigate the effects of fenofibrate and bezafibrate on the risk of development of diabetic retinopathy (DR) in patients with type 2 diabetes and dyslipidemia. Japanese working age patients with type 2 diabetes and dyslipidemia were extracted from the Nihon University School of Medicine Clinical Data Warehouse. These patients were divided into three groups: control group (n=2549), fenofibrate group (n=40), and bezafibrate group (n=135). Multivariate logistic regression analysis was performed to assess the association between fibrates and the development of DR. After adjustment for covariates, fenofibrate showed no association with the risk of DR [adjusted odds ratio (OR), 0.160; 95% CI, 0.021-1.209; p=0.0758]. Bezafibrate also showed no association with the risk of DR (adjusted OR, 0.731; 95% CI, 0.411-1.299; p=0.2855). However, poor control of hemoglobin A1c (HbA1c ≥8.0%; adjusted OR, 3.623; 95% CI, 2.649-4.956; p

Objective: Adherence to lipid-lowering drugs could be challenging in our patients as it is in the general population, which is described as low as 25%. Our aim was to evaluate adherence to statins and to investigate clinical event impact on it. Methods: This retrospective study on HIV+ patients attending to Clinic of Modena (Italy) was conducted in order to evaluate characteristics, clinical events, and adherence on lipid-lowering drugs. All drugs for comorbidities are distributed by the hospital pharmacy and recorded in an electronical database. Adherence was also evaluated in patients who were supplied with antilipemics in external pharmacies through phone calls. Patients were considered adherent if the percentage of correct time of drug refill was >80%. Findings: Totally 1123 patients were evaluated. Lipid-lowering drugs (statins, fenofibrate, and omega-3 oil) were prescribed in 242 patients (21.5%). Prescription occurred mainly in those who were older, males, and Italians. Two hundred of them (82.6%) used statins alone, 23 (9.5%) only fenofibrate or omega-3 oil, and 19 (7.8%) a combination of both drugs. The median adherence was 90% while patients with adherence >80% resulted 153 (63.2%). Forty-six (19%) had a clinical history of cardiovascular events; 59% of them, placed in secondary prophylaxis, and 76%, already in treatment, continued to adhere. No differences in terms of adherence according to the type of drug distribution (hospital pharmacy or outside pharmacies) were found. Conclusion: Linking the supply of these drugs to that of antiretrovirals led to a good level of adherence higher than that described in the general population. The majority of the patients who experienced a cardiovascular event remain adherent to the prescribed therapy.

Objective:Describe the treatment of the patient with atherogenic dyslipidaemia (AD) in routine Primary Care clinical practice. Methodology:Observational, descriptive, cross-sectional study based on a structured questionnaire. The content of the questionnaire was based on a review of the literature and was validated by 3 AD experts. It included 23 questions and was addressed to primary care physicians. This sub study will analyze questions related to the treatment of AD. Results:A total of 1,029 Primary Care physicians (67.06% men) participated in the study. Most work in urban areas (55.9%) and attended to a mean of 79.9 (SD: 89.85) patients with AD per month. Most (95.63%) considered that the first step in treatment is lifestyle modification. For the AD approach associated with obesity in primary prevention, 74% of the participants advised lifestyle modifications and in turn evaluated the need for pharmacological treatment. In patients with moderate elevations of LDL-C and DA treated with statins, 90% of doctors associated fibrates. In these patients, 93% agreed or fully agreed that fenofibrate is the most appropriate fibrate for their combination with statins. 19% consider the genfibrocil association. In patients in secondary prevention and AD, treated with statins with LDL-C in therapeutic objectives, the majority of participants (94.46%) added a fibrate and 70% combined statins and fibrates from the start of treatment. Conclusions:Although the level of inculcation of knowledge about the therapeutic management of AD is highly acceptable in some cases, there are parts that need to be modified, especially the poor association of statins with genfibrocil.

Objective To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients. Methods A total of 983 gout patients on fenofibrate treatment who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020 were retrospectively enrolled from the electronic records system. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during the treatment period were assessed by a generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr. Results A total of 100 (10.2%) patients experienced an increase in SCr ≥0.3 mg/dl within 6 months after fenofibrate initiation. The median change of SCr in the whole cohort was 0.11 mg/dl [interquartile range (IQR) 0.03–0.20], whereas it was 0.36 (0.33–0.45) in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) [odds ratio (OR) 2.39 (95% CI 1.48, 3.86)] and tophus [OR 2.29 (95% CI 1.39, 3.78)] were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily increased, serum urate and triglyceride concentrations decreased using the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, the SCr increase in 65% of patients was reversed after an average of 49 days off the drug. Conclusions This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout needs additional research.

Context Fenofibrate provides limited cardiovascular (CV) benefits in the general population; however, little is known about its benefit among advanced chronic kidney disease (CKD) patients. Objective This study compared outcomes among advanced CKD patients treated with fenofibrate, statins, a combination of both, and none of these. Methods This national cohort study was based on Taiwan’s National Health Insurance Research Database. Patients younger than 20 years with advanced CKD were identified and further divided into 4 groups according to treatment. The inverse probability of treatment weighting was used to balance baseline characteristics. Patients received fenofibrate, statins, a combination of fenofibrate and statins, or none of these in the 3 months preceding the advanced CKD date. Main outcome measures included all-cause mortality, CV death, and incidence of permanent dialysis. Results The fenofibrate and statin groups exhibited a lower risk of CV death (fenofibrate vs nonuser: hazard ratio [HR]: 0.84; 95% CI, 0.75-0.94; statins vs nonuser: HR: 0.94; 95% CI, 0.90-0.97) compared with the nonuser group. The fenofibrate group further exhibited the lowest incidence of permanent dialysis (fenofibrate vs nonuser: subdistribution HR [SHR]: 0.78; 95% CI, 0.77-0.80; statins vs fenofibrate: SHR: 1.27; 95% CI, 1.26-1.29; combination vs fenofibrate: SHR: 1.15; 95% CI, 1.13-1.17). Furthermore, the combined administration of fenofibrate and high-intensity statins exhibited a lower risk of major adverse cardiac and cerebrovascular events. Conclusion For patients with advanced CKD, continuing fenofibrate may provide a protective effect on CV outcomes equal to that of statins, and it may further delay the need for permanent dialysis. The combination of fenofibrate and high-intensity statins may have additional benefits.

We had previously reported on S-1-induced hypertriglyceridemia. Here, we report fluorouracil-induced hypertriglyceridemia in a patient with capecitabine-induced hypertriglyceridemia and the corresponding therapeutic process. A woman in her forties who had experienced grade 3 hypertriglyceridemia due to oxaliplatin + capecitabine was administered fluorouracil ± oxaliplatin + levofolinate calcium + panitumumab; however, grade 4 hypertriglyceridemia occurred after the thirteenth administration. Bezafibrate normalized the elevation. Chemotherapy cessation resulted in its decrease to normal, and bezafibrate was stopped. Nine months after cessation, treatment with fluorouracil + irinotecan + levofolinate calcium + ramucirumab was initiated. After four cycles of treatment, her serum triglyceride levels increased again to grade 3, and then, fenofibrate was administered, resulting in a significant decrease to grade 1–2. Serum triglyceride levels significantly reduced after cessation of the prior fluorouracil-containing regimen, although its elevation was observed again following the latter treatment. Therefore, fluorouracil-induced hypertriglyceridemia was strongly speculated in this case. We have speculated that the most probable cause of tegafur and capecitabine-induced hypertriglyceridemia is fluorouracil or its metabolic enzymes since their end product is fluorouracil in the previous report. Results from this patient suggest that our supposition was correct. Fibrates administration, cessation of the treatment, and monitoring of serum triglyceride level was effective in this case as well as previous reports. Fluorouracil-induced hypertriglyceridemia is associated with the one caused by tegafur and capecitabine and presents the possibility of severe complications. Elucidation of its exact mechanism and epidemiological features is needed for better understanding.

Lesions caused by high glucose (HG), hypoxia/reperfusion (H/R), and the coexistence of both conditions in cardiomyocytes are linked to an overproduction of reactive oxygen species (ROS), causing irreversible damage to macromolecules in the cardiomyocyte as well as its ultrastructure. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, promotes beneficial activities counteracting cardiac injury. Therefore, the objective of this work was to determine the potential protective effect of fenofibrate in cardiomyocytes exposed to HG, H/R, and HG+H/R. Cardiomyocyte cultures were divided into four main groups: (1) control (CT), (2) HG (25 mM), (3) H/R, and (4) HG+H/R. Our results indicate that cell viability decreases in cardiomyocytes undergoing HG, H/R, and both conditions, while fenofibrate improves cell viability in every case. Fenofibrate also decreases ROS production as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH) subunit expression. Regarding the antioxidant defense, superoxide dismutase (SOD Cu2+/Zn2+ and SOD Mn2+), catalase, and the antioxidant capacity were decreased in HG, H/R, and HG+H/R-exposed cardiomyocytes, while fenofibrate increased those parameters. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) increased significantly in treated cells, while pathologies increased the expression of its inhibitor Keap1. Oxidative stress-induced mitochondrial damage was lower in fenofibrate-exposed cardiomyocytes. Endothelial nitric oxide synthase was also favored in cardiomyocytes treated with fenofibrate. Our results suggest that fenofibrate preserves the antioxidant status and the ultrastructure in cardiomyocytes undergoing HG, H/R, and HG+H/R preventing damage to essential macromolecules involved in the proper functioning of the cardiomyocyte.

Fibrates and statins have been widely used to reduce triglyceride and cholesterol levels, respectively. Besides its lipid-lowering effect, the side effect of muscle atrophy after fibrate administration to humans has been demonstrated in some studies. Combination therapy with fibrates and statins also increases the risk of rhabdomyolysis. FoxO1, a member of the FoxO forkhead type transcription factor family, is markedly upregulated in skeletal muscle in energy-deprived states and induces muscle atrophy via the expression of E3-ubiquitine ligases. In this study, we investigated the changes in FoxO1 and its targets in murine skeletal muscle with fenofibrate treatment. High doses of fenofibrate (greater than 0.5% (wt/wt)) over one week increased the expression of FoxO1 and its targets in the skeletal muscles of mice and decreased skeletal muscle weight. These fenofibrate-induced changes were diminished in the PPARα knockout mice. When the effect of combination treatment with fenofibrate and lovastatin was investigated, a significant increase in FoxO1 protein levels was observed despite the lack of deterioration of muscle atrophy. Collectively, our findings suggest that a high dose of fenofibrate over one week causes skeletal muscle atrophy via enhancement of FoxO1, and combination treatment with fenofibrate and lovastatin may further increase FoxO1 protein level.

Fenofibrate is a marketed fibric acid derivative for lipid-lowering in patients with lipid disorders. Numerous studies have proven fenofibrate had a certain effect on serum uric acid, here we conducted this study to quantitatively assess the effect of fenofibrate intervention in modulating serum uric acid concentration and the influence on serum creatinine. The PubMed, Embase and Cochrane were systematically searched for randomized controlled trials update to January, 2020. Primary endpoints focused on serum uric acid concentration and serum creatinine concentration. The pooled effects were calculated as weighted mean difference (WMD) by a random-effects model. Finally, 9 studies representing 487 patients were included in the meta-analysis. The meta-analysis demonstrated that fenofibrate significantly reduced serum uric acid levels (WMD -1.32 mg/dL, 95%CI -1.61 to -1.03, p < 0.001) and an elevated level in serum creatinine (WMD 0.09 mg/dL, 95%CI 0.02 to 0.15, p < 0.001) following fenofibrate therapy compared with placebo. The present study provided strong evidence that fenofibrate intervention exerted a significant reduction on serum uric acid and a mild increase on serum creatinine. Meta-analysis suggested that there were no significant association between the serum uric acid lowering effect with either dose or treatment duration. Overall, our meta-analysis ascertained that fenofibrate have potential therapeutic effects in patients with lipid metabolic abnormalities but with mid nephrotoxicity. There is strong evidence to provide future direction of practical application and clinical researches of fenofibrate.

De novo phospholipogenesis, mediated by choline-ethanolamine phosphotransferase 1 (CEPT1), is essential for phospholipid activation of transcription factors such as peroxisome proliferator–activated receptor α (PPARα) in the liver. Fenofibrate, a PPARα agonist and lipid-lowering agent, decreases amputation incidence in patients with diabetes. Because we previously observed that CEPT1 is elevated in carotid plaque of patients with diabetes, we evaluated the role of CEPT1 in peripheral arteries and PPARα phosphorylation (Ser12). CEPT1 was found to be elevated in diseased lower-extremity arterial intima of individuals with peripheral arterial disease and diabetes. To evaluate the role of Cept1 in the endothelium, we engineered a conditional endothelial cell (EC)–specific deletion of Cept1 via induced VE-cadherin-CreERT2–mediated recombination (Cept1Lp/LpCre+). Cept1Lp/LpCre+ ECs demonstrated decreased proliferation, migration, and tubule formation, and Cept1Lp/LpCre+ mice had reduced perfusion and angiogenesis in ischemic hind limbs. Peripheral ischemic recovery and PPARα signaling were further compromised by streptozotocin-induced diabetes and ameliorated by feeding fenofibrate. Cept1 endoribonuclease-prepared siRNA decreased PPARα phosphorylation in ECs, which was rescued with fenofibrate but not PC16:0/18:1. Unlike Cept1Lp/LpCre+ mice, Cept1Lp/LpCre+Ppara−/− mice did not demonstrate hind-paw perfusion recovery after feeding fenofibrate. Therefore, we demonstrate that CEPT1 is essential for EC function and tissue recovery after ischemia and that fenofibrate rescues CEPT1-mediated activation of PPARα.

The activation of the renin-angiotensin system (RAS) participates in the development of metabolic syndrome (MetS) and in heart failure. PPAR-alpha activation by fenofibrate reverts some of the effects caused by these pathologies. Recently, nonclassical RAS components have been implicated in the pathogenesis of hypertension and myocardial dysfunction; however, their cardiac functions are still controversial. We evaluated if the nonclassical RAS signaling pathways, directed by angiotensin III and angiotensin-(1-7), are involved in the cardioprotective effect of fenofibrate during ischemia in MetS rats. Control (CT) and MetS rats were divided into the following groups: (a) sham, (b) vehicle-treated myocardial infarction (MI-V), and (c) fenofibrate-treated myocardial infarction (MI-F). Angiotensin III and angiotensin IV levels and insulin increased the aminopeptidase (IRAP) expression and decreased the angiotensin-converting enzyme 2 (ACE2) expression in the hearts from MetS rats. Ischemia activated the angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin receptor 1 (AT1R) and angiotensin III/angiotensin IV/angiotensin receptor 4 (AT4R)-IRAP axes. Fenofibrate treatment prevented the damage due to ischemia in MetS rats by favoring the angiotensin-(1-7)/angiotensin receptor 2 (AT2R) axis and inhibiting the angiotensin III/angiotensin IV/AT4R-IRAP signaling pathway. Additionally, fenofibrate downregulated neprilysin expression and increased bradykinin production. These effects of PPAR-alpha activation were accompanied by a reduction in the size of the myocardial infarct and in the activity of serum creatine kinase. Thus, the regulation of the nonclassical axis of RAS forms part of a novel protective effect of fenofibrate in myocardial ischemia.

Acute pancreatitis (AP) is one of the most common gastrointestinal-related causes of hospitalization in the USA, accounting for more than 200,000 admissions annually. Although mild and moderate cases usually improve within a week, severe AP conditions could lead to life-threatening pancreatic necrosis, multiple-organ dysfunction, and be fatal in some cases. Excessive alcohol use and gallstones are the two leading causes, nonetheless other systemic complication could also lead to AP. Hypertriglyceridemia is an important, yet uncommon, cause/risk factor of AP, especially when associated with heavy alcohol use. Additionally, the level of triglycerides (TGs) was found to be an important factor of determining the method and duration of treatment. Here we present a case of 38-year-old obese and active smoker male with hypertension and alcohol use disorder presented with a chief complaint of 2 weeks of progressive sharp epigastric pain. His medical history was significant of opioid use disorder that is maintained on methadone therapy. Computed tomography (CT) scan of the abdomen and pelvis revealed infiltration of the fat along the pancreatic tail and distal body with focus of decreased enhancement in the very distal pancreatic tail, which could represent a small infarct or phlegmon. In addition, laboratory data was significant of elevated lipase level (> 1,000 mg/dL), which together with the CT result confirmed the diagnosis of AP. Additional laboratory workup revealed extremely high level of TGs of > 2,000 mg/dL. The patient was subsequently transferred to the intensive care unit for management of hypertriglyceridemia. He was started on insulin therapy along with supportive treatment for the management of pancreatitis. Hypertriglyceridemia and pancreatitis rapidly improved over the course of hospitalization period and no additional intervention was needed. He was successfully discharged on fenofibrate.

Background: Silent uncontrolled hypertension can cause major organ damage. Case presentation: A 42-year-old hypertensive male used fenofibrate to lower his triglyceride levels; however, the investigation revealed that it caused a significant increase in the desire and ingestion of greasy food items which caused fluctuating high blood pressure. Correction of the dietary regimen and a modification in the usual recommended drug dose led to a significant positive development of the medical case. Specifically, it was successful in adjusting the systolic and diastolic blood pressure components and blood test parameters, and was effective in correcting the glucose criteria back to the acceptable standard range. Conclusion: This is the first evidence in the literature on a poorly controlled hypertension case associated indirectly with fenofibrate.

Despite widespread phototherapy usage, many new-born infants remain in need of other invasive lines of therapy, such as intravenous immunoglobulins and exchange transfusions. Assessment of the efficacy and the safety of adding fenofibrate to phototherapy for the treatment of pathological jaundice in full-term infants. We conducted a double blinded randomized control study on 180 full-term infants with pathological unconjugated hyperbilirubinemia admitted to the NICU at Mansoura University Children’s Hospital. They were randomly assigned to receive either oral fenofibrate 10 mg/kg/day for 1 day or 2 days or placebo in addition to phototherapy. The primary outcome was total serum bilirubin values after 12, 24, 36, 48, and 72 h from intervention. Secondary outcomes were total duration of treatment, need for exchange transfusions and intravenous immunoglobulin, exclusive breast-feeding on discharge, and adverse effects of fenofibrate. This study was registered at www.clinicaltrials.gov (NCT04418180). A total of 180 full-term infants were included, 60 in each group. Infants in group I and II showed significant reduction of bilirubin levels at 36, 48, and 72 h from intervention compared to group III, respectively. Fenofibrate administration was associated with significantly shorter duration of phototherapy, shorter hospital stay, and higher frequency of exclusive breast-feeding compared to phototherapy alone. Fenofibrate as an adjuvant to phototherapy in term neonate with pathological jaundice is well tolerated and associated with significant reduction of serum bilirubin levels, a shorter duration of phototherapy, shorter hospital stay and higher frequency of exclusive breast-feeding, without significant adverse effects in either the single or double dosage.

Background: Fenofibrates were not previously known to affect renal function tests until some reports indicated that these drugs may lead to a decrease in renal function. Likewise, the nephrotoxic effect of fibrates remains to be vague and unclear. Guidelines regarding fenofibrate dosing in renal impairment vary internationally. Patients and methods: A prospective cohort study over 6 months with a total of 80 patients on fibrates divided into 2 groups, 40 of which received statins, and the other 40 continued on fibrates. All patients were subjected to full history, clinical examination, and complete baseline labs. The KFTs including serum creatinine and eGFR were measured at 0, 1, 2, and 6-months intervals and lipid profile at 0,3,6 months serially in both groups. Results: Out of the baseline values of KFTs, the statin group showed a significant decrease in all kidney function values including mean serum creatinine by (0.9mg/dL, P=0.001) and an increase in eGFR (8.9 mL/min/1.73 m2, P

Objective Experimental studies suggest that fenofibrate prevents abdominal aortic aneurysm (AAA) development by lowering aortic osteopontin (OPN) concentration and reducing the number of macrophages infiltrating the aortic wall. The current study examined the effects of a short course of fenofibrate on AAA pathology in people with large AAAs awaiting aortic repair. Methods This randomised double blind parallel trial included male and female participants aged ≥ 60 years who had an asymptomatic AAA measuring ≥ 50 mm and were scheduled to undergo open AAA repair. Participants were allocated to fenofibrate (145 mg/day) or matching placebo for at least two weeks before elective AAA repair. Blood samples were collected at recruitment and immediately prior to surgery. AAA biopsies were obtained during aortic surgery. The primary outcomes were (1) AAA OPN concentration; (2) serum OPN concentration; and (3) number of AAA macrophages. Exploratory outcomes included circulating and aortic concentrations of other proteins previously associated with AAA. Outcomes assessed at a single time point were compared using logistic regression. Longitudinal outcomes were compared using linear mixed effects models. Results Forty-three participants were randomised. After three withdrawals, 40 were followed until the time of surgery (21 allocated fenofibrate and 19 allocated placebo). As expected, serum triglycerides reduced significantly from recruitment to the time of surgery in participants allocated fenofibrate. No differences in any of the primary and exploratory outcomes were observed between groups. Conclusion A short course of 145 mg of fenofibrate/day did not lower concentrations of OPN or aortic macrophage density in people with large AAAs.

A feared adverse effect of dyslipidaemia therapy by fibrates is myopathy. We examined the effect of fenofibrate (FF) on protein and amino acid metabolism. Rats received a low (50 mg/kg, LFFD) or high (300 mg/kg, HFFD) dose of FF or vehicle daily by oral gavage. Blood plasma, liver, and soleus and extensor digitorum longus muscles were analysed after 10 days. The FF‐treated rats developed hepatomegaly associated with increased hepatic carnitine and ATP and AMP concentrations, decreased protein breakdown, and decreased concentrations of DNA and triglycerides. HFFD increased plasma ALT and AST activities. The weight and protein content of muscles in the HFFD group were lower compared with controls. In muscles of the LFFD group there were increased ATP and decreased AMP concentrations; in the HFFD group AMP was increased. In both FF‐treated groups there were increased glycine, phenylalanine, and citrulline and decreased arginine and branched‐chain keto acids (BCKA) in blood plasma. After HFFD there were decreased levels of branched‐chain amino acids (BCAA; valine, leucine and isoleucine), methionine, and lysine and increased homocysteine. Decreased arginine and increased glycine concentrations were found in both muscles in FF‐treated animals; in HFFD‐treated animals lysine, methionine, and BCAA were decreased. We conclude that FF exerts protein‐anabolic effects on the liver and catabolic effects on muscles. HFFD causes signs of hepatotoxicity, impairs energy and protein balance in muscles, and decreases BCAA, methionine, and lysine. It is suggested that increased glycine and decreased lysine and methionine levels are due to activated carnitine synthesis; decreased BCAA and BCKA levels are due to increased BCAA oxidation.

The present study evaluated the protective effects of fenofibrate on liver function, oxidant-antioxidant balance, and insulin resistance (IR) in rats fed high-fat-high-fructose diet (HFFD). Twenty-four male Sprague-Dawley rats (110-130 gm) were allocated into four equal groups (n = 6). Rats in group I were fed a normal diet for 4 weeks. Rats in group II were fed a normal diet with fenofibrate at 50 mg/kg/day orally for four weeks. Rats in group III were fed a normal diet mixed with 25% palm oil and given 60% fructose solution orally for 4 weeks. Rats in group IV were fed a normal diet mixed with 25% palm oil, 60% oral fructose solution, and fenofibrate at 50 mg/kg/day orally for four weeks. After experimental induction, serum and liver tissue samples were collected to determine lipid profiles, glycemic status, antioxidant status, oxidative and stress markers, and histopathology of liver tissues. The results of the present study revealed that fenofibrate prevents the occurrence of fatty liver, enhancing glycemic status, decreasing oxidative stress, and improving antioxidant status. It can be concluded that fenofibrate has a lipotropic and antidiabetic role.

Objective: To study the effect and safety of Fenofibrate in uncomplicated hyperbilirubinemia in newborn with 6-month follow-up. Materials and Methods: This is a randomized controlled clinical trial conducted in 60 normal term neonates admitted for uncomplicated hyperbilirubinemia in NICU at Sir T G Hospital, Bhavnagar from January 2012 to December 2012. The data included: age, sex, total serum bilirubin (TSB), weight and duration of phototherapy. All neonates enrolled in the study received phototherapy. They were divided in two groups of 30 each: control group A and group B receiving Fenofibrate (100 mg/kg single dose). There was statistically insignificant difference between the parameters of age, sex, weight and TSB between the two groups at hospitalization. Data was analyzed by using appropriate statistical methods. Results: Mean values for total serum bilirubin in Fenofibrate group B at 24 and 48 hours after admission were significantly lower than those for control group A (p

Introduction: Hypertriglyceridemia is known as an independent risk factor for coronary artery disease (CAD). Fenofibrate that is used for the treatment of hypertriglyceridemia can prevent cardiovascular events in patients with CAD. However, there is little information regarding the vascular effects of fenofibrate on arterial wall stiffness in patients with hypertriglyceridemia and without CAD, diabetes mellitus (DT), and hypertension (HT). The objective of this study is to evaluate the effects of fenofibrate treatment on the arterial stiffness in the patients with pure hypertriglyceridemia. Patients and Methods: We included 37 patients with hypertriglyceridemia without CAD, HT, and DT in this study. We performed pre- and post-treament physical examination of the patients and took their blood samples. Patients were allocated fenofibrate for a duration of 168 ± 14 days for its administration. We assessed arterial stiffness by aortic pulse wave velocity (PWV) using a SphygmoCor device. Importantly, we estimated central arterial pressure waveform parameters by radial artery applanation tonometry and used augmentation index (AIx) as a measure of wave reflections. Results: Fenofibrate treatment resulted in significantly greater reductions in total cholesterol (201.3 ± 61.0 mg/dL vs. 270.0 ± 93.4 mg/dL), triglycerides (261.3 ± 234.3 mg/dL vs. 704.7 ± 338.7 mg/dL), and the C/H levels (5.3 ± 2.6 vs. 7.2 ± 1.9, respectively) as compared with the pretreatment levels (p< 0.001). There was a tendency of high-sensitivity C-reactive protein (hs-CRP) to decline after fenofibrate treatment as change in hs-CRP was significant (0.47 ± 0.41 mg/dL vs. 0.32 ± 0.31 mg/dL respectively, p< 0.01). AIx remained unchanged from the pretreatment levels (24.2% ± 12.4% vs. 22.0% ± 11.4%, respectively, p> 0.05). There was a significant reduction in PWV after fenofibrate treatment (11.3 ± 2.9 m/s vs. 9.2 ± 2.2 m/s, p= 0.001). Conclusion: Fenofibrate treatment appears to effectively improve the arterial wall stiffness in the patients with pure hypertriglyceridemia.

Diabetic retinopathy (DR) is a kind of irreversible visual impairment common in adults. Several studies have confirmed the ability of fenofibrate (FNB) to mitigate DR pathology. miR-21 has also been shown to improve the hemodynamics of DR model rats. Presently, it is not clear whether FNB can play a therapeutic role in DR via regulating miR-21, and we will supplement this gap through this research. First, in this research, we constructed an in vitro model of DR by inducing ARPE-19 cells with high glucose (HG). After successful induction, the proliferation ability of ARPE-19 cells was inhibited, the apoptosis ability was enhanced, and the oxidative stress index (reactive oxygen species, ROS) level was increased. Subsequently, we discovered that the cell vitality was significantly improved, the apoptosis ability was inhibited, and oxidative stress injury was improved under FNB intervention in the in vitro model of DR. In mechanism, FNB can improve the viability of DR model in vitro and alleviate the oxidative stress injury induced by HG through down-regulating miR-21 or up-regulating IL-6R. Furthermore, miR-21 has a targeted regulatory relationship with IL6R, which can negatively regulate the level of IL6R. Based on the above, we conclude that FNB can improve the viability and alleviate oxidative stress injury of DR model in vitro via regulating the miR-21-IL6R axis.

The sodium salt of isosteviol (STVNa) is a beyerane diterpene synthesized through acid hydrolysis of stevioside. STVNa improves multiple types of tissue injuries. However, it is not known how isosteviol sodium affects high-fat and high cholesterol diet (HFD)-induced kidney. Therefore, in this study we examined the potential molecular mechanism underlying STVNa mediated protective effect against high fat/high cholesterol-induced kidney dysfunction in HFD-induced kidney injury. Sprague-Dawley (SD) rats were allocated into six groups: the normal group, HFD group and HFD treated with three doses of STVNa, fenofibrate treatment group. The results indicated that HFD induced kidney injury evident by a 60% increase in serum creatinine (CRE) leves. In addition, there was a significant accumulation of triglycerides (approx. 60%), fatty acids (approx. 50%) and total cholesterol (approx. 2.5 fold) in the kidneys. STVNa inhibited HFD-induced kidney injury evident by reducing the increased levels of serum CRE. Specifically, STVNa attenuated HFD-induced kidney injury by inhibiting inflammation, oxidative stress, and apoptosis. These findings indicate that STVNa has a therapeutic potential for HFD-induced kidney dysfunction. The mechanisms of this pharmacological effect are through the inhibition of inflammation, oxidative stress and apoptosis.

Reverse cholesterol transport (RCT) and transintestinal cholesterol efflux (TICE) are two important pathways for body cholesterol elimination. We studied these pathways in an animal model of diabetes and obesity (ob/ob) where HDL function is compromised as a result of hyperglycemia, low-grade inflammation and oxidative stress. Co-treatment of ob/ob mice with PPAR-α (fenofibrate) and LXR (T0901317) agonists increased fecal cholesterol by 12-fold; PPAR-α and LXR agonists individually showed 2.6- and 4.0-fold fecal cholesterol excretion, respectively. We investigated the mechanism of synergistic efficacy of PPAR-α and LXR agonists in fecal cholesterol excretion. LXR agonist and the combination of PPAR-α and LXR agonists had greater HDL-C elevation. Ex vivo cholesterol efflux showed correlation with the fecal cholesterol excretion but was not sufficient to explain 12-fold increases in the fecal cholesterol in the co-treated mice. Therefore, we examined TICE to explain the 12-fold increases in the fecal cholesterol. A strong positive correlation of fecal cholesterol with ATP binding cassette transporter G5 (ABCG5) and G8 and anegative correlation with NPC1L1 was observed. ABCG5, G8 and NPC1L1 are involved in intestinal cholesterol absorption. The extent of influence of PPAR-α and LXR agonists on RCT and TICE was distinctly different. PPAR-α agonist increased fecal cholesterol primarily by influencing TICE, while LXR agonist influenced fecal cholesterol excretion via both RCT and TICE mechanisms. Synergistic efficacy on fecal cholesterol excretion following co-treatment with PPAR-α and LXR agonists occurred through a combination of RCT, TICE, and the key enzyme in bile synthesis, cholesterol 7-α hydroxylase (cyp7a1). These results suggest that cholesterol efflux, biliary cholesterol excretion, and TICE collectively contributed to the 12-fold increases in the fecal cholesterol excretion in ob/ob mice co-treated with PPAR-α and LXR agonists.

Glycerol‐3‐phosphate dehydrogenase 1 deficiency is a rare autosomal recessive disorder caused by mutations in the GPD1 gene (GPD1; OMIM*138420). Very few cases are reported in literature. It usually manifests in early infancy with transient hypertriglyceridemia, hepatomegaly, steatosis, and fibrosis. We report the case of a 16‐year‐old boy followed since the age of 1 year for hepatomegaly, elevated liver enzymes, and persistent hypertriglyceridemia. Abdominal ultrasound showed diffuse liver echogenicity and liver biopsy disclosed cirrhosis with micro and macrovesicular steatosis. Next‐generation sequencing for metabolic and genetic liver diseases was conducted with the identification of the homozygous mutation c.895G>A in GPD1 gene resulting in the aminocidic substitution p.G299R. Considering the persistent and progressive increase of plasma triglycerides, fenofibrate treatment was started at 15 years of age allowing triglyceride level reduction in the following 1‐year follow‐up.

Recent clinical trials in children with acute lymphoblastic leukemia (ALL) indicate that severe hypertriglyceridemia (> 1000 mg/dL) during therapy is associated with increased frequency of symptomatic osteonecrosis. Interventions to lower triglycerides have been considered, but there have been no pre-clinical studies investigating impact of lowering triglycerides on osteonecrosis risk, nor whether such interventions interfere with the antileukemic efficacy of ALL treatment. We utilized our clinically relevant mouse model of dexamethasone-induced osteonecrosis to determine if fenofibrate decreased osteonecrosis. To test whether fenofibrate affected the antileukemic efficacy of dexamethasone, we utilized a BCR-ABL+ model of ALL. Serum triglycerides were reduced with fenofibrate throughout treatment, with the most pronounced 4.5-fold decrease at week 3 (p

Objective: Though epidemiological data suggest that an elevated triglyceride (TG) level may be a risk factor for coronary artery disease (CAD), there is still insufficient clinical evidence. This study was designed to evaluate the real-life efficacy and side effects of fibrate treatment for hypertriglyceridemia seen in a lipid clinic, as well as cardiovascular and diabetic outcomes. Methods: This retrospective study evaluated patients who were followed-up for a diagnosis of hypertriglyceridemia at the lipid outpatient clinic of the Ege University Cardiology Department between 1997 and 2018. Data of demographic and clinical characteristics were obtained from hospital records. All patients (n=240) with at least 1 year of follow-up were included in the analysis. During follow-up, patients were treated with fenofibrate, and less frequently, gemfibrozile (14 patients), at different doses according to the TG level and disease severity. Results: Of the study population, 23% had CAD, 21% were diabetic, and 52% were obese. On admission, 20% were using fibrates and 17% were on statins. The mean admission lipid levels were TG: 281+-194 mg/dL, low-density lipoprotein cholesterol: 115+-37 mg/dL, high-density lipoprotein (HDL) cholesterol: 43+-13 mg/dL, and non-HDL cholesterol: 166+-42 mg/dL. The mean length of follow-up was 5.3+-4.7 years (range: 1–16 years). A total of 8 (4.3%) patients had adverse effects during follow-up (1 on statin combination and 7 on fibrates alone). The side effects observed were an elevation of liver enzymes in 3, myalgia in 2, insomnia in 1, malaise in 1, and a skin rash in 1 patient. No rhabdomyolysis or myopathy was seen. During follow-up, diabetes developed in 14 and cardiovascular disease (CVD) in 14 patients. The cumulative non-HDL cholesterol level was significantly high in patients who developed diabetes or CVD. Receiver operating curve analysis indicated that a cumulative non-HDL cholesterol value of 1016 mg/dL was predictive of the development of diabetes mellitus or CVD with 85% sensitivity and 70% specificity. Conclusion: In real life, long-term fibrate use is effective and safe. The cumulative non-HDL cholesterol burden can be used to assess the efficacy of treatment as a simple and easily calculated method. Large studies are needed to further clarify the value of this parameter in predicting the development of both diabetes and CVD.

High-quality health care not only includes timely access to effective new therapies but timely abandonment of therapies when they are found to be ineffective or unsafe. Little is known about changes in use of medications after they are shown to be ineffective or unsafe. In this study, we examine changes in use of two medications: fenofibrate, which was found to be ineffective when used with statins among patients with Type 2 diabetes (ACCORD lipid trial); and dronedarone, which was found to be unsafe in patients with permanent atrial fibrillation (PALLAS trial). We examine the patient and provider characteristics associated with a decline in use of these medications. Using Medicare fee-for-service claims from 2008 to 2013, we identified two cohorts: patients with Type 2 diabetes using statins (7 million patient-quarters), and patients with permanent atrial fibrillation (83 thousand patient-quarters). We used interrupted time-series regression models to identify the patient- and provider-level characteristics associated with changes in medication use after new evidence emerged for each case. After new evidence of ineffectiveness emerged, fenofibrate use declined by 0.01 percentage points per quarter (95% CI − 0.02 to − 0.01) from a baseline of 6.9 percent of all diabetes patients receiving fenofibrate; dronedarone use declined by 0.13 percentage points per quarter (95% CI − 0.15 to − 0.10) from a baseline of 3.8 percent of permanent atrial fibrillation patients receiving dronedarone. For dronedarone, use declined more quickly among patients dually-enrolled in Medicare and Medicaid compared to Medicare-only patients (P

The purpose of this study was to investigate the protective role of peroxisome proliferator–activated receptor α (PPARα) against diabetic keratopathy and corneal neuropathy. Corneal samples were obtained from human donors with and without diabetes. Streptozotocin-induced diabetic rats and mice were orally treated with PPARα agonist fenofibrate. As shown by immunohistochemistry and Western blotting, PPARα was downregulated in the corneas of humans with diabetes and diabetic rats. Immunostaining of β-III tubulin demonstrated that corneal nerve fiber metrics were decreased significantly in diabetic rats and mice, which were partially prevented by fenofibrate treatment. As evaluated using a Cochet-Bonnet aesthesiometer, corneal sensitivity was significantly decreased in diabetic mice, which was prevented by fenofibrate. PPARα−/− mice displayed progressive decreases in the corneal nerve fiber density. Consistently, corneal sensitivity was decreased in PPARα−/− mice relative to wild-type mice by 21 months of age. Diabetic mice showed increased incidence of spontaneous corneal epithelial lesion, which was prevented by fenofibrate while exacerbated by PPARα knockout. Western blot analysis revealed significantly altered neurotrophic factor levels in diabetic rat corneas, which were partially restored by fenofibrate treatment. These results indicate that PPARα protects the corneal nerve from degeneration induced by diabetes, and PPARα agonists have therapeutic potential in the treatment of diabetic keratopathy.

Summary A 19-year-old female presented at 25-weeks gestation with pancreatitis. She was found to have significant hypertriglyceridaemia in context of an unconfirmed history of familial hypertriglyceridaemia. This was initially managed with fasting and insulin infusion and she was commenced on conventional interventions to lower triglycerides, including a fat-restricted diet, heparin, marine oil and gemfibrozil. Despite these measures, the triglyceride levels continued to increase as she progressed through the pregnancy, and it was postulated that she had an underlying lipoprotein lipase defect. Therefore, a multidisciplinary decision was made to commence therapeutic plasma exchange to prevent further episodes of pancreatitis. She underwent a total of 13 sessions of plasma exchange, and labour was induced at 37-weeks gestation in which a healthy female infant was delivered. There was a rapid and significant reduction in triglycerides in the 48 h post-delivery. Subsequent genetic testing of hypertriglyceridaemia genes revealed a missense mutation of the LPL gene. Fenofibrate and rosuvastatin was commenced to manage her hypertriglyceridaemia postpartum and the importance of preconception counselling for future pregnancies was discussed. Hormonal changes in pregnancy lead to an overall increase in plasma lipids to ensure adequate nutrient delivery to the fetus. These physiological changes become problematic, where a genetic abnormality in lipid metabolism exists and severe complications such as pancreatitis can arise. Available therapies for gestational hypertriglyceridaemia rely on augmentation of LPL activity. Where there is an underlying LPL defect, these therapies are ineffective and removal of triglyceride-rich lipoproteins via plasma exchange should be considered. Learning points: Hormonal changes in pregnancy, mediated by progesterone,oestrogen and human placental lactogen, lead to a two- to three-fold increase in serum triglyceride levels. Pharmacological intervention for management of gestational hypertriglyceridaemia rely on the augmentation of lipoprotein lipase (LPL) activity to enhance catabolism of triglyceride-rich lipoproteins. Genetic mutations affecting the LPL gene can lead to severe hypertriglyceridaemia. Therapeutic plasma exchange (TPE) is an effective intervention for the management of severe gestational hypertriglyceridaemia and should be considered in cases where there is an underlying LPL defect. Preconception counselling and discussion regarding contraception is of paramount importance in women with familial hypertriglyceridaemia.

Ingestion of fructose-rich diets has been associated with the increase in the global prevalence of obesity, dyslipidemia and non-alcoholic fatty liver disease across all age groups. Phytochemicals from the plant Moringa oleifera Lam. reportedly therapeutically reduce obesity, correct hyperlipidemia and decrease excess hepatic lipid accumulation in adults. In light of the increasing prevalence of diet-induced metabolic dysfunction in children, this study was designed to investigate the protective effects of a methanolic leaf extract of M. oleifera on fructose-induced obesity and hepatic lipid accumulation in growing female rats. Fifty-one 21-day-old female Sprague Dawley rats were weaned and randomly allocated to six treatment groups. The rats had ad libitum access to commercial standard rat food. In addition, they also had plain drinking water (negative control; C), or a 20% fructose solution (H), or 400 mg.kg− 1M. oleifera absolute methanolic leaf extract daily with or without fructose solution (M + H or Mo), or 100 mg.kg− 1 fenofibrate daily with or without fructose solution for drinking (F + H or FNF). Growth parameters, circulating metabolites, visceral fat pads, hepatic lipid storage, and biochemical markers of general health were assessed after 10 weeks of the interventions. A significant increase in circulating triglycerides (mmol.l− 1) (2.30 ± 0.43 vs 1.70 ± 0.30; P .05, ANOVA). Visceral fat pads (g) were significantly lower in the fenofibrate treated group (FNF) compared to those on combined fructose and M. oleifera (M + H) (11.00 ± 3.00 vs 17.00 ± 3.40; P .05) in plasma cholesterol, however, rats on fenofibrate alone had lower (P .05, ANOVA), HOMA-IR index (P > .05, ANOVA), plasma creatinine (P > .05, ANOVA), body mass gain (P > .05, ANOVA), linear growth (tibia and femur length, P > .05), body mass index (P > .05, ANOVA) and waist circumference (P > .05, ANOVA) between the different treatment groups. The prophylactic potential of M. oleifera methanolic leaf extract should be considered as an alternative prophylactic natural agent against non-alcoholic fatty liver disease, and thus needs to be further explored in humans.

Objective: Endothelial dysfunction is afflicted to the maturation of arteriosclerosis and type 2 diabetes mellitus (T2DM) vascular complications. This study designed to evaluate the impact of fenofibrate adjuvant therapy on endothelial dysfunction and cardiovascular risk in patients with T2DM. Methods: Seventy-five subjects were recruited from the Internal Medicine Department of Tanta University Hospital. The participants were classified into three groups: Group 1 (control group), 25 healthy subjects; Group 2, 25 T2DM patients received glimepiride/metformin (2:500 mg/day); and Group 3, 25 T2DM patients received glimepiride/metformin (2:500 mg/day)+fenofibrate (300 mg/day). Patients were assessed before and 3 months after intervention for the determination of body mass index (BMI), blood pressure, glycemic picture (hemoglobin A1C % and homeostatic model assessment of insulin resistant), lipid panel, Castelli’s risk index (CRI-I and CRI-II), albumin-to-creatinine ratio (ACR), and endothelial dysfunction biomarkers (asymmetric dimethylarginine [ADMA] and Syndecan-1 (SDC-1)]. Data were statistically analyzed by one-way analysis of variance; p

Gastrin, secreted by stomach G cells in response to ingested sodium, stimulates the renal cholecystokinin B receptor (CCKBR) to increase renal sodium excretion. It is not known how dietary sodium, independent of food, can increase gastrin secretion in human G cells. However, fenofibrate (FFB), a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, increases gastrin secretion in rodents and several human gastrin-secreting cells, via a gastrin transcriptional promoter. We tested the following hypotheses: (1.) the sodium sensor in G cells plays a critical role in the sodium-mediated increase in gastrin expression/secretion, and (2.) dopamine, via the D1R and PPAR-α, is involved. Intact human stomach antrum and G cells were compared with human gastrin-secreting gastric and ovarian adenocarcinoma cells. When extra- or intracellular sodium was increased in human antrum, human G cells, and adenocarcinoma cells, gastrin mRNA and protein expression/secretion were increased. In human G cells, the PPAR-α agonist FFB increased gastrin protein expression that was blocked by GW6471, a PPAR-α antagonist, and LE300, a D1-like receptor antagonist. LE300 prevented the ability of FFB to increase gastrin protein expression in human G cells via the D1R, because the D5R, the other D1-like receptor, is not expressed in human G cells. Human G cells also express tyrosine hydroxylase and DOPA decarboxylase, enzymes needed to synthesize dopamine. G cells in the stomach may be the sodium sensor that stimulates gastrin secretion, which enables the kidney to eliminate acutely an oral sodium load. Dopamine, via the D1R, by interacting with PPAR-α, is involved in this process.

We investigated lipid metabolism in PXB-cells, which are human primary hepatocytes isolated from liver-humanized mice, and HepG2 and HuH-7 human hepatoma cell lines. Lipoprotein levels were higher in PXB-cells than in the 2 other cell lines, and PXB-cells mainly released triglycerides and cholesterol as very low density lipoprotein (VLDL), similar to actual liver tissue, whereas the major lipoprotein released from the 2 hepatoma cell lines was LDL. RT-PCR analysis demonstrated that the gene expression levels of apolipoprotein B100 (ApoB100), the apolipoprotein of VLDL/LDL, were similar in PXB-cells and HepG2 cells, while the overexpression of ApoC2, ApoC3, and ApoE, which are components of VLDL, but not LDL, was observed in PXBcells. A protein immunoassay revealed that ApoB100 levels secreted from PXB-cells and HuH-7 cells were similar; however, ApoC3 levels were higher in PXB-cells than in the two other cell lines. We also examined the anti-lipidemic activities of fenofibrate using this assay system. Fenofibrate suppressed lipoprotein production from PXB-cells in a dose-dependent manner mainly by activating the β-oxidation pathway. These results suggest that PXB-cells produce high levels of lipoproteins and are suitable for screening anti-lipidemic agents.

Aims: To compare the efficacy of pemafibrate (PF) and fenofibrate (FF) in treating dyslipidemia. Methods: A comprehensive search was performed on the public database to identify relevant randomized controlled trials (RCTs), which compared the effects of PF and FF treatment in lipid parameters among patients with dyslipidemia. Mean difference (MD) and 95% confidence intervals (CI) were pooled for continuous outcomes, whereas odds ratio (OR) and 95% CI were calculated for dichotomous outcomes. Results: Three RCTs were included with a total of 744 patients (PF=547 and FF=197). Compared with the FF group (100mg/day), PF group (0.05 to 0.4mg/day) had a better effect on reducing triglycerides (TGs) (MD, -8.66; 95%CI, -10.91 to -6.41), very low-density lipoprotein cholesterol (VLDL-C, MD, -12.19; 95%CI, -15.37 to - 9.01), remnant lipoprotein cholesterol (MD, -13.16; 95%CI, -17.62 to -8.69), apolipoprotein-B48 (ApoB48, MD, -12.74; 95%CI, -17.71 to -7.76) and ApoCIII (MD, -6.25; 95%CI, -11.85 to -0.64). Although a slightly LDL-Cincreasing effect was found in PF-treated group (MD, 3.10; 95%CI, -0.12 to 6.09), the levels of HDL-C (MD, 3.59; 95%CI, 1.65 to 5.53) and ApoAI (MD, 1.60; 95%CI, 0.38 to 2.82) were significantly increased in the PF group. However, no significant difference was found in the level of total cholesterol (MD, 0.01; 95%CI, -1.37 to - 1.39), non-HDL-C (MD, -0.06; 95%CI, -1.75 to 1.63), ApoB (MD, 0.39; 95%CI, -1.37 to 2.15) and ApoAII (MD, 3.31; 95%CI, -1.66 to 8.29) between the two groups. In addition, the incidence of total adverse events (OR, 0.68; 95%CI, 0.53 to 0.86) and adverse drug reactions (OR, 0.36; 95%CI, 0.24 to 0.54) was lower in the PF group than that in the FF group. Conclusions: Pemafibrate tends to have better efficacy in treating dyslipidemia than fenofibrate.

A trombocitopenia induzida por fármacos é uma entidade frequente na prática clínica. No entanto, pela sua gravidade torna-se imperativo distinguir a trombocitopenia não-imune das formas imunomediadas potenci-almente ameaçadoras da vida. Os autores descrevem o caso clínico raro de um homem de 79 anos que se apresentou com púrpura trombocitopénica grave não-trombótica e gengivorragia ao sexto dia de introdu-ção diária de fenofibrato na sua medicação habitual. Foi feita exclusão do fármaco e administrada metilprednisolona 125 mg endovenoso durante três dias com resolução completa do quadro estabelecendo uma probabilidade elevada de diagnóstico. A trombocitopenia associada ao fármaco é reportada pelos fabricantes como um evento extremamente raro. Este é o segundo caso reportado de trombocitopenia imune ao fenofibrato, tendo o primeiro caso sido publicado em 2015.