• Atlantic salmon
• gene expreesion
• heritabiity
• lipid metabolism
• liver fat

• Norges Forskningsråd

• Inter-organ crosstalk
• MASLD
• Mechanism
• Metabolic disorders
• Prevention and treatment

• Humans
• Inflammation/metabolism
• Inflammation/pathology
• Metabolic Diseases/metabolism
• Metabolic Diseases/pathology
• Metabolic Diseases/physiopathology
• Disease Progression
• Animals
• Fatty Liver/metabolism
• Fatty Liver/pathology
• Lipid Metabolism
• Liver/metabolism
• Liver/pathology

• lipid
• nonalcoholic fatty liver disease
• prediabetes
• risk factors
• type 2 diabetes mellitus

• Humans
• Diabetes Mellitus, Type 2/blood
• Diabetes Mellitus, Type 2/epidemiology
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/metabolism
• Non-alcoholic Fatty Liver Disease/blood
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/metabolism
• Female
• Male
• Prediabetic State/blood
• Prediabetic State/epidemiology
• Prediabetic State/metabolism
• Middle Aged
• Nutrition Surveys
• Adult
• Risk Factors
• Lipids/blood
• Biomarkers/blood
• Aged
• Cross-Sectional Studies
• Blood Glucose/metabolism
• Blood Glucose/analysis

• MASH
• MASLD
• cholesterol metabolism
• hepatoprotection
• natural products

• 82104479 the National Natural Science Foundation of China

• Humans
• Non-alcoholic Fatty Liver Disease
• Carcinoma, Hepatocellular
• Liver Neoplasms
• Receptors, Cytoplasmic and Nuclear

• Roux-en-Y gastric bypass
• bile acid
• cholesterol
• liver
• transcriptome

• Humans
• Gastric Bypass/methods
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/surgery
• Transcriptome
• Obesity/complications
• Cholesterol
• Homeostasis
• Inflammation/complications
• Obesity, Morbid/complications

• R21 AR080233 NIAMS NIH HHS

• Cardiometabolic diseases
• Cardiometabolic risk factors
• Mendelian randomization
• Remnant cholesterol

• Humans
• Mendelian Randomization Analysis
• Cholesterol
• Risk Factors
• Atrial Fibrillation
• Myocardial Ischemia
• Genome-Wide Association Study
• Polymorphism, Single Nucleotide

• National Medical Research Council
• National Research Foundation Singapore

• Animals
• Gemfibrozil/pharmacology
• Lipidoses
• Liver/diagnostic imaging
• Lizards/metabolism
• Succinic Acid/metabolism
• Ultrasonography

• University of Guelph - Ontario Veterinary College - Pet Trust Foundation

• Association
• Cardiovascular diseases
• Cardiovascular health
• Cardiovascular health metrics
• Health care quality indicators
• Health status
• Non-alcoholic fatty liver disease
• Risk factors

• 2019R1A4A1028155 Ministry of Science and ICT
• 2020K2A9A2A08000190 The National Research Foundation of Korea

• inflammation
• lipid peroxidation
• metabolites
• obesity
• oxidative stress
• reactive oxygen species
• volatile organic compounds

• adipsin
• hepatic steatosis
• metabolic dysfunction-associated fatty liver disease
• metabolic risk abnormalities

• the State Key Program of the National Natural Science Foundation of China
• the National Natural Science Foundation of China

Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative diseases and cancers, particularly the CVD in which the accumulation of lipids (mainly the cholesteryl esters) within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually. More and more studies have shown that lowering cholesterol level, especially low-density lipoprotein cholesterol level, protects cardiovascular system and prevents cardiovascular events effectively. Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All the processes should be precisely controlled by the multiple regulatory pathways. Based on the regulation of cholesterol homeostasis, many interventions have been developed to lower cholesterol by inhibiting cholesterol biosynthesis and uptake or enhancing cholesterol utilization and excretion. Herein, we summarize the historical review and research events, the current understandings of the molecular pathways playing key roles in regulating cholesterol homeostasis, and the cholesterol-lowering interventions in clinics or in preclinical studies as well as new cholesterol-lowering targets and their clinical advances. More importantly, we review and discuss the benefits of those interventions for the treatment of multiple diseases including atherosclerotic cardiovascular diseases, obesity, diabetes, nonalcoholic fatty liver disease, cancer, neurodegenerative diseases, osteoporosis and virus infection.

Investigation on protective effects of Panax notoginseng against obesity and its related mechanisms is incomplete. Present study aimed to investigate the potential anti-obesity effect of the total saponins (PNS) and ethanolic extract of P. notoginseng (PNE).

Six-week-old male C57BL/6J mice received 45% kcal fat diet for 12 weeks to induce obesity. Oral administration of PNS and PNE at 20 mg/kg/day was applied for the last 4 weeks in the obese mice. Lipid profile was determined by ELISA. Histological examination was performed in liver and fat tissues. Protein levels were measured by Western blot.

PNS and PNE did not cause weight loss. PNE but not PNS decreased the mass of epididymal and retroperitoneal white adipose tissue, accompanied by a reduction in adipocyte hypertrophy. PNS and PNE improved lipid profile by reducing the concentrations of triglyceride, total cholesterol and low-density lipoprotein cholesterol in plasma or liver samples. PNS and PNE also relieved fatty liver in obese mice. PNS and PNE inhibited expression and phosphorylation of endoplasmic reticulum (ER) stress-responsive proteins in hypertrophic adipose tissue.

PNS and PNE can regulate ER stress-mediated apoptosis and inflammation to alleviate obesity.

• Endoplasmic reticulum stress
• Obesity
• Panax notoginseng
• Saponins
• White adipose tissue

• Blood pressure
• Diabetes
• Glycine
• Hyperlipidemia
• Metabolic syndrome
• Obesity

• Exercise
• Glycine/metabolism
• Glycine/therapeutic use
• Humans
• Life Style
• Metabolic Syndrome/drug therapy
• Obesity/therapy

• discriminant model
• fatty liver disease
• lipoproteins
• remnant lipoprotein cholesterol

• Adult
• Cholesterol
• Humans
• Lipoproteins
• Liver Diseases
• Male
• Retrospective Studies
• Triglycerides

• 24-hydroxycholesterol
• aging
• brain
• cholesterol
• liver

• Aging
• Alzheimer Disease/metabolism
• Animals
• Apolipoproteins E/genetics
• Apolipoproteins E/metabolism
• Brain/metabolism
• Cholesterol/metabolism
• Cohort Studies
• Humans
• Liver/metabolism
• Mice
• Rats

Sterols, bile acids, and acylcarnitines are key players in human metabolism. Precise annotations of these metabolites with mass spectrometry analytics are challenging because of the presence of several isomers and stereoisomers, variability in ionization, and their relatively low concentrations in biological samples. Herein, we present a sensitive and simple qualitative LC–MS/MS (liquid chromatography with tandem mass spectrometry) method by utilizing a set of pure chemical standards to facilitate the identification and distribution of sterols, bile acids, and acylcarnitines in biological samples including human stool and plasma; mouse ileum, cecum, jejunum content, duodenum content, and liver; and pig bile, proximal colon, cecum, heart, stool, and liver. With this method, we detected 24 sterol, 32 bile acid, and 27 acylcarnitine standards in one analysis that were separated within 13 min by reversed-phase chromatography. Further, we observed different sterol, bile acid, and acylcarnitine profiles for the different biological samples across the different species. The simultaneous detection and annotation of sterols, bile acids, and acylcarnitines from reference standards and biological samples with high precision represents a valuable tool for screening these metabolites in routine scientific research.

• LC–MS/MS
• acylcarnitine
• annotation
• bile acid
• sterol

• circadian disruption
• liver
• mammary
• pregnancy
• transcriptome

Patients with primary biliary cholangitis (PBC) often have comorbid dyslipidemia, and determining the degree of hepatic steatosis can help predict the risk of cardiovascular events in PBC patients. The aim of our study was to analyze the characteristics of lipid distribution and the degree of hepatic steatosis in PBC.

We retrospectively analyzed 479 cases of PBC, chronic hepatitis B (CHB), chronic hepatitis C (CHC), non-alcoholic fatty liver disease (NAFLD), and healthy subjects (Normal) diagnosed by liver biopsy or definitive clinical diagnosis. Controlled attenuation parameter (CAP) values were applied to assess the degree of steatosis of the liver, and lipid levels were also compared in the five cohorts.

We found that among the five groups of subjects, the PBC group had the lowest CAP values (P < 0.001), and the high-density lipoprotein cholesterol (HDL-C) level in the PBC group was higher than normal, CHC and CHB group (P = 0.004, P = 0.033, P < 0.001, respectively).In the multivariate linear analysis, only BMI (β = 1.280, P = 0.028), ALP (β = − 0.064, P = 0.012), TBA (β = − 0.126, P = 0.020), TG (β = 12.520, P = 0.000), HDL-C (β = − 11.338, P = 0.001) and LDL-C (β = 7.012, P = 0.002) were independent predictors of CAP.

Among PBC, CHB, CHC, NAFLD and healthy subjects, PBC had the lowest degree of hepatic steatosis and higher HDL-C levels, all of which were found to be protective factors against atherosclerosis and cardiovascular risk and would provide a valuable reference for the risk of developing cardiovascular events in PBC patients.

The online version contains supplementary material available at 10.1186/s12876-021-01974-4.

• Controlled attenuation parameter
• Dyslipidemia
• High-density lipoprotein cholesterol
• Liver steatosis
• Primary biliary cholangitis

One of the focuses of non-alcoholic fatty liver disease (NAFLD) treatment is exercise. Randomized controlled trials investigating the effects of exercise without dietary changes on NAFLD-related clinical parameters (liver parameters, lipid metabolism, glucose metabolism, gut microbiota, and metabolites) were screened using the PubMed, Scopus, Web of Science, and Cochrane databases on 13 February 2020. Meta-analyses were performed on 10 studies with 316 individuals who had NAFLD across three exercise regimens: aerobic exercise, resistance training, and a combination of both. No studies investigating the role of gut microbiota and exercise in NAFLD were found. A quality assessment via the (RoB)2 tool was conducted and potential publication bias, statistical outliers, and influential cases were identified. Overall, exercise without significant weight loss significantly reduced the intrahepatic lipid (IHL) content (SMD: −0.76, 95% CI: −1.04, −0.48) and concentrations of alanine aminotransaminase (ALT) (SMD: −0.52, 95% CI: −0.90, −0.14), aspartate aminotransaminase (AST) (SMD: −0.68, 95% CI: −1.21, −0.15), low-density lipoprotein cholesterol (SMD: −0.34, 95% CI: −0.66, −0.02), and triglycerides (TG) (SMD: −0.59, 95% CI: −1.16, −0.02). The concentrations of high-density lipoprotein cholesterol, total cholesterol (TC), fasting glucose, fasting insulin, and glycated hemoglobin were non-significantly altered. Aerobic exercise alone significantly reduced IHL, ALT, and AST; resistance training alone significantly reduced TC and TG; a combination of both exercise types significantly reduced IHL. To conclude, exercise overall likely had a beneficial effect on alleviating NAFLD without significant weight loss. The study was registered at PROSPERO: CRD42020221168 and funded by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 813781.

• aerobic exercise
• glucose metabolism
• lipid metabolism
• meta-analysis
• non-alcoholic fatty liver disease
• resistance training
• systematic review
• transaminases

• Exercise/physiology
• Exercise Therapy/methods
• Gastrointestinal Microbiome
• Glucose/metabolism
• Humans
• Lipid Metabolism
• Liver/metabolism
• Non-alcoholic Fatty Liver Disease/physiopathology
• Non-alcoholic Fatty Liver Disease/therapy
• Randomized Controlled Trials as Topic
• Resistance Training
• Treatment Outcome

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m²) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m²) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor‐beta‐induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD.

• MAST4HEALTH
• Mastiha
• inflammation
• non-alcoholic fatty liver disease
• nutrigenetics
• oxidative stress
• randomized clinical trial

• alanine aminotransferase
• biomarker
• insulin resistance
• metabolic syndrome
• triglyceride to high-density lipoprotein cholesterol ratio

• Alanine Transaminase/blood
• Biomarkers/blood
• Female
• Humans
• Insulin Resistance
• Japan/epidemiology
• Lipoproteins, HDL/blood
• Male
• Metabolic Syndrome/diagnosis
• Metabolic Syndrome/epidemiology
• Triglycerides/blood

In this narrative review, we will appraise if modification of the length of bypassed small intestine based on measured total small intestinal length could optimize the outcomes of the laparoscopic Roux-en-Y gastric bypass (LRYGB). We provide a summary of carefully selected studies to serve as examples and to draw tentative conclusions of the effects of LRYGB on remission of comorbidities. As the heterogeneity of the included studies varied in terms of outcomes, type of study, length of the bypassed small intestine, and the follow-up, a common endpoint could not be defined for this narrative article. To achieve efficient metabolic outcomes, it is important to carefully choose the small intestine length excluded from the food passage suited best to each individual patient.

• Comorbidity
• Gastric bypass
• Intestine
• Obesity
• Triglycerides
• Weight Loss

• HCC
• NAFLD
• NASH
• cholesterol
• obesity

• R01 DK120714 NIDDK NIH HHS
• R01CA234128 NCI NIH HHS
• R01CA211794 NCI NIH HHS
• P42ES010337 NIEHS NIH HHS
• P42 ES010337 NIEHS NIH HHS
• R01DK120714 NIDDK NIH HHS
• R01 CA234128 NCI NIH HHS

Liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are markers of hepatic dysfunction and fatty liver disease. Although ALT and AST have been suggested as risk factors for cardiovascular disease, their role as predictors of mortality after acute myocardial infarction (AMI) has not been established. The objective of this study was to investigate the predictive value of ALT and AST for mortality in patients with AMI.

We analyzed records of 712 patients with AMI and no known liver disease treated at the Department of Cardiovascular Center in the First Hospital of Jilin University. The primary outcome was all-cause in-hospital mortality. Relationships between primary outcome and various risk factors, including serum transaminase levels, were assessed using multivariate logistic regression analysis.

Age (P < 0.001), hypertension (P = 0.034), prior myocardial infarction (P < 0.001), AST (P < 0.001), ALT (P < 0.001), creatinine (P = 0.007), blood urea nitrogen (P = 0.006), and troponin I (P < 0.001) differed significantly between ST-segment elevation myocardial infarction (STEMI) and non-STEMI. The following factors were associated with an increased risk of in-hospital all-cause mortality in patients with AMI: ALT ≥ 2ULN (adjusted odds ratio [AOR] 2.240 [95% confidence interval (CI), 1.331–3.771]; P = 0.002); age ≥ 65 year (AOR 4.320 [95% CI 2.687–6.947]; P < 0.001); increased fasting plasma glucose (FPG) (AOR 2.319 [95% CI 1.564–3.438]; P < 0.001); elevated D-dimer (AOR 2.117 [95% CI 1.407–3.184]; P < 0.001); elevated fibrinogen (AOR 1.601 [95% CI 1.077–2.380]; P = 0.20); and reduced estimated glomerular filtration rate (eGFR) (AOR 2.279 [95% CI 1.519–3.419]; P < 0.001).

Our findings demonstrated that elevated ALT was independently associated with increased in-hospital all-cause mortality in patients with AMI. Other risk factors were increased age, FPG, D-dimer, and fibrinogen and decreased eGFR.

• Acute myocardial infarction
• Alanine transaminase
• Fasting plasma glucose
• Liver enzymes
• Mortality
• eGFR

• Alzheimer's disease
• DEGs
• Gene interaction networks
• Liver-Brain Axis
• NAFLD
• TUBB5

Non-alcoholic fatty liver disease (NAFLD) is a major health problem associated with obesity and other features of the metabolic syndrome including insulin resistance and dyslipidemia. The accumulation of lipids in hepatocytes causes liver damage and triggers inflammation, fibrosis, and cirrhosis. Beside fatty acids and triglycerides, evidence showed an increased accumulation of free cholesterol in the liver with subsequent toxic effects contributing to liver damage. The maintenance of cholesterol homeostasis in the body requires a balance between several pathways responsible for cholesterol synthesis, transport and conversion into bile acids. Intestinal absorption is also one of the major determinants of cholesterol homeostasis. The nature of changes in cholesterol homeostasis associated with NAFLD has been a subject of extensive investigations. In this article, we will attempt to provide a brief overview of the current knowledge about the disturbances in cholesterol metabolism associated with NAFLD and discuss how certain molecular targets of these pathways could be exploited for the treatment of this multifactorial disease.

• NPC1L1
• bile acids
• ezetimibe
• fatty liver
• statins

• Bavachinin
• Cholesterol synthesis inhibition
• FDFT1
• HMG-CoA synthase
• Squalene synthase

Non-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker.

Eighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control. One patient was excluded due to low RT-PCR signal.

Compared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, low-density-lipoprotein cholesterol and non-high-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism–related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379.

Serum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.

• Adult
• Aged
• Biomarkers/blood
• Female
• Humans
• Hypercholesterolemia/blood
• Hypercholesterolemia/etiology
• Male
• MicroRNAs/blood
• Middle Aged
• Non-alcoholic Fatty Liver Disease/blood
• Non-alcoholic Fatty Liver Disease/complications
• Up-Regulation

• Japan Society for the Promotion of Science

• cellular stress
• cholesterol
• hepatic steatosis
• lipogenesis
• mule ducks

• hesperidin
• inflammation
• insulin resistance
• liver enzymes
• liver steatosis
• nonalcoholic fatty liver disease

• Alanine Transaminase/blood
• Alkaline Phosphatase/blood
• Double-Blind Method
• Female
• Hesperidin/pharmacology
• Hesperidin/therapeutic use
• Humans
• Liver/pathology
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/pathology

• Farnesoid X receptor
• Liver X receptors
• Niemann-Pick C1-like 1
• Non-alcoholic fatty liver disease

• Adult
• Aged
• Case-Control Studies
• Down-Regulation
• Duodenum/chemistry
• Female
• Humans
• Leukocytes, Mononuclear/chemistry
• Liver X Receptors/analysis
• Liver X Receptors/genetics
• Male
• Membrane Transport Proteins/analysis
• Middle Aged
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/metabolism
• Young Adult

• High-density lipoproteins
• fatty liver index
• high-density lipoprotein subclasses
• lecithin–cholesterol acyltransferase
• paraoxonase 3

• BMI
• cardiovascular disease
• diabetes mellitus
• hyperlipidemia
• intestinal disease
• kidney disease
• liver disease
• metabolic syndrome
• non-cholesterol sterols
• plant sterols

• Body composition
• Exercise
• Obesity
• Waist circumference

• Abdominal Fat/diagnostic imaging
• Abdominal Fat/metabolism
• Abdominal Fat/pathology
• Abdominal Muscles/diagnostic imaging
• Abdominal Muscles/metabolism
• Abdominal Muscles/pathology
• Absorptiometry, Photon
• Adolescent
• Adult
• Aged
• Body Composition/physiology
• Body Mass Index
• Cross-Over Studies
• Exercise Therapy/instrumentation
• Exercise Therapy/methods
• Female
• Humans
• Leisure Activities
• Male
• Middle Aged
• Obesity/prevention & control
• Organ Size
• Overweight/metabolism
• Overweight/therapy
• Play and Playthings
• Waist Circumference/physiology
• Walking/physiology
• Young Adult

This paper presents a comprehensive review of hypolipidemic mechanism of polysaccharides from natural sources.