Lipid metabolism is a complex physiological process, which is closely related to nutrient regulation, hormone balance and endocrine function. It involves the interactions of multiple factors and signal transduction pathways. Lipid metabolism disorder is one of the main mechanisms to induce a variety of diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, hepatitis, hepatocellular carcinoma and their complications. At present, more and more studies have found that the "dynamic modification" of N⁶-adenylate methylation (m⁶A) on RNA represents a new "post-transcriptional" regulation mode. m⁶A methylation modification can occur in mRNA, tRNA, ncRNA, etc. Its abnormal modification can regulate gene expression changes and alternative splicing events. Many latest references have reported that m⁶A RNA modification is involved in the epigenetic regulation of lipid metabolism disorder. Based on the major diseases induced by lipid metabolism disorders, we reviewed the regulatory roles of m⁶A modification in the occurrence and development of those diseases. These overall findings inform further in-depth investigations of the underlying molecular mechanisms regarding the pathogenesis of lipid metabolism disorders from the perspective of epigenetics, and provide reference for health prevention, molecular diagnosis and treatment of related diseases.
Humans ; Methylation ; Epigenesis, Genetic ; Lipid Metabolism/genetics* ; Lipid Metabolism Disorders/genetics* ; Liver Neoplasms ; RNA

OBJECTIVES: Perfluorooctanoic acid (PFOA) can cause lipid metabolism disorders in animal body and affect the lipolysis and synthesis of fatty acids. Peroxisome proliferators-activated receptor (PPAR) plays an extremely important role in this process. This study aims to explore the effects of PFOA on liver lipid metabolism disorders in Sprague Dewley (SD) rats and the expression of PPAR. METHODS: A total of 40 male SD rats were randomly divided into 4 groups (n=10 in each group): a control group (ddH₂O), a low-dose PFOA group [PFOA 1.25 mg/(kg·d)], a middle-dose PFOA group [PFOA 5.00 mg/(kg·d)], and a high-dose PFOA group [PFOA 20.00 mg/(kg·d)]. The rats were fed with normal diet, and PFOA exposure were performed by oral gavage for 14 days, and the rats were observed, weighted and recorded every day during the exposure. After the exposure, the blood was collected, and the livers were quickly stripped after the rats were killed. Part of the liver tissues were fixed in 4% paraformaldehyde for periodic acid-schiff (PAS) staining; the contents of HDLC, LDLC, TG, TC in serum and liver tissues, as well as the activities of their related enzymes were assayed; The expression levels of cyclic adenosine monophosphate-response element binding protein (Cbp), general control of amino acid synthesis 5-like 2 (Gcn5L2), peroxidation peroxisome proliferation factor activated receptor γ (PPAR), silent information regulator 1 (Sirt1) and human retinoid X receptor alpha 2 (Rxrα2) ) were detected by Western blotting. RESULTS: After 14 days of PFOA exposure, the PAS staining positive particles in the cytoplasm and nucleus of SD rats in the medium and high dose groups were significantly reduced compared with the control group. The serum levels of LDLC and TC in the low-dose and middle-dose groups were significantly reduced compared with the control group (all P<0.05), while the high-dose group showed an increasing tendency, without siginificant difference (P>0.05), there was no significant difference in HDLC and TG (both P>0.05). The activities of alkaline phosphatase (AKP) and alanine aminotransferase (ALT) were increased significantly (both P<0.05) compared with control group; the ratio of ALT/aspartate aminotransferase (AST) in the high-dose group was increased significantly (P<0.05), there was no significant difference in LDH and TG (both P>0.05); the HDLC content in the liver tissues in the high-dose group was significantly reduced, compared with the control group (P<0.05); the TC contents in the liver tissues in the low, medium and high-dose groups were significantly increased (all P<0.05), there was no significant difference in LDLC and TG (both P>0.05); the AKP activity in the livers in the medium and high-dose groups was significantly increased (both P<0.05), there was no siginificant difference in LDH, ALT, and the ratio of ALT/AST (all P>0.05); the protein expression levels of Ppar γ, Cbp and Rxrα2 in the liver in the high dose groups were significantly down-regulated compared with the control group (all P<0.05), while the protein expression levels of Sirt1 were significantly up-regulated (all P<0.05). CONCLUSIONS PFOA exposure can cause lipid metabolism disorder and glycogen reduction in SD rat livers, which may be related to the activation of Sirt1 and inhibition of Ppar γ expression, leading to affecting the normal metabolism of fatty acids and promoting glycolysis.
Animals ; Caprylates ; Fatty Acids/pharmacology* ; Fluorocarbons ; Lipid Metabolism ; Lipid Metabolism Disorders/metabolism* ; Liver/metabolism* ; Male ; PPAR gamma ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism*

OBJECTIVE: To compare the therapeutic effect of different animal bile powders on lipid metabolism disorders induced by high-fat diet in rats, and analyze the bioactive components of each animal bile powder. METHODS: Sixty Sprague-Dawley rats were randomly divided into 6 groups (n=10): normal diet control group, high-fat diet model group, high-fat diet groups orally treated with bear, pig, cow and chicken bile powders, respectively. Serum biochemical markers from the abdominal aorta in each group were analyzed. Changes in the body weight and liver weight were recorded. Pathohistological changes in the livers were examined. High performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was used to determine the composition of bioactive components in each animal bile powder. RESULTS: Treatment with different types of animal bile powders had different inhibitory effects on high-fat diet-induced increase of body weight and/or liver weight in rats, most notably in bear and pig bile powders (P<0.05). High-fat diet induced lipid metabolism disorder in rats, which could be reversed by treatment with all kinds of bile powders. Bear bile and chicken bile showed the most potent therapeutic effect against lipid metabolism disorder. Cow and bear bile effectively alleviated high-fat diet induced liver enlargement and discoloration, hepatocyte swelling, infiltration of inflammatory cells and formation of lipid vacuoles. Bioactive component analysis revealed that there were significant differences in the relative content of taurocholic acid, taurodeoxycholic acid and ursodeoxycholic acid among different types of animal bile. Interestingly, a unique component with molecular weight of 496.2738 Da, whose function has not yet been reported, was identified only in bear bile powder. CONCLUSIONS Different animal bile powders had varying therapeutic effect against lipid metabolism disorders induced by high-fat diet, and bear bile powder demonstrated the most effective benefits. Bioactive compositions were different in different types of animal bile with a novel compound identified only in bear bile powder.
Animals ; Bile/metabolism* ; Biomarkers/metabolism* ; Body Weight ; Cattle ; Diet, High-Fat ; Female ; Lipid Metabolism ; Lipid Metabolism Disorders/metabolism* ; Lipids/analysis* ; Liver/metabolism* ; Powders ; Rats ; Rats, Sprague-Dawley ; Swine ; Taurodeoxycholic Acid/metabolism* ; Ursidae/metabolism* ; Ursodeoxycholic Acid/metabolism*

OBJECTIVE: To investigate the changes of lipid metabolism and stress response of adult C.elegans exposed to non-freezing low temperature and explore the possible mechanism. METHODS: The survival rate and activity of adult C.elegans cultured at 20℃ or 4℃ were observed.Lipid metabolism of the cultured adult C.elegans was evaluated using oil red O staining and by detecting the expressions of the genes related with lipid metabolism.The effects of low temperature exposure on stress level of adult C.elegans were evaluated using mitochondrial fluorescence staining and by detecting the expression levels of stress-related genes and antioxidant genes at both the mRNA and protein levels. RESULTS: The lifespan and activity of adult C.elegans exposed to low temperature were significantly reduced with decreased lipid accumulation (P < 0.05) and decreased expressions of genes related with fatty acid synthesis and metabolism (fat-5, fat-6, fat-7, fasn-1, nhr-49, acs-2 and aco-1;P < 0.01).Cold stress significantly increased the expressions of heat shock proteins hsp-70 and hsp16.2(P < 0.05) but lowered the number of mitochondria (P < 0.0001) and the expressions of atfs-1, sod-2, sod-3 and gpx-1(P < 0.05).Knockout of fat-5, nhr-49 or both fat-5 and fat-6 obviously enhanced the sensitivity of C.elegans to cold stress as shown by further reduced activity (P < 0.05) and reduced survival rate at 24 h (P < 0.0001) under cold stress. CONCLUSION Exposure to a low temperature at 4℃ results in lowered lipid metabolism of adult C.elegans accompanied by a decreased mitochondrial number and quality control ability, which triggers high expressions of stress-related genes and causes reduction of antioxidant capacity, thus callsing lowered activity and reduced lifespan of C.elegans.
Animals ; Antioxidants/metabolism* ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/genetics* ; Cold-Shock Response ; Lipid Metabolism ; Lipid Metabolism Disorders ; Longevity/genetics*

This study explored the molecular mechanism underlying the Gegen Qinlian Decoction(GQD) promoting the differentiation of brown adipose tissue(BAT) to improve glucose and lipid metabolism disorders in diabetic rats. After the hypoglycemic effect of GQD on diabetic rats induced by high-fat diet combined with a low dose of streptozotocin was confirmed, the total RNA of rat BAT around scapula was extracted. Nuclear transcription genes Prdm16, Pparγc1α, Pparα, Pparγ and Sirt1, BAT marker genes Ucp1, Cidea and Dio2, energy expenditure gene Ampkα2 as well as BAT secretion factors Adpn, Fndc5, Angptl8, IL-6 and Rbp4 were detected by qPCR, then were analyzed by IPA software. Afterward, the total protein from rat BAT was extracted, and PRDM16, PGC1α, PPARγ, PPARα, SIRT1, ChREBP, AMPKα, UCP1, ADPN, NRG4, GLUT1 and GLUT4 were detected by Western blot. The mRNA expression levels of Pparγc1α, Pparα, Pparγ, Ucp1, Cidea, Ampkα2, Dio2, Fndc5, Rbp4 and Angptl8 were significantly increased(P<0.05) and those of Adpn and IL-6 were significantly decreased(P<0.05) in the GQD group compared with the diabetic group. In addition, Sirt1 showed a downward trend(P=0.104), whereas Prdm16 tended to be up-regulated(P=0.182) in the GQD group. IPA canonical pathway analysis and diseases-and-functions analysis suggested that GQD activated PPARα/RXRα and SIRT1 signaling pathways to promote the differentiation of BAT and reduce the excessive lipid accumulation. Moreover, the protein expression levels of PRDM16, PGC1α, PPARα, PPARγ, SIRT1, ChREBP, AMPKα, UCP1, GLUT1, GLUT4 and NRG4 were significantly decreased in the diabetic group(P<0.01), which were elevated after GQD intervention(P<0.05). Unexpectedly, the expression of ADPN protein in the diabetic group was up-regulated(P<0.01) as compared with the control group, which was down-regulated after the administration with GQD(P<0.01). This study indicated that GQD promoted BAT differentiation and maturity to increase energy consumption, which reduced the glucose and lipid metabolism disorders and thereby improved diabetes symptoms.
Adipose Tissue, Brown ; Animals ; Diabetes Mellitus, Experimental/genetics* ; Drugs, Chinese Herbal ; Fibronectins ; Glucose ; Lipid Metabolism ; Lipid Metabolism Disorders ; Rats

OBJECTIVE: Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy. METHODS: In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected. RESULTS: The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism. CONCLUSION It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.
Adipose Tissue ; drug effects ; metabolism ; Animals ; Autophagy ; drug effects ; Body Weight ; drug effects ; Diet, High-Fat ; adverse effects ; Diethylhexyl Phthalate ; toxicity ; Endocrine Disruptors ; toxicity ; Female ; Lipid Metabolism ; drug effects ; Lipid Metabolism Disorders ; chemically induced ; Liver ; drug effects ; metabolism ; Male ; Rats, Wistar ; STAT1 Transcription Factor ; metabolism ; TYK2 Kinase ; metabolism

PURPOSE: Metabolic syndrome (MS) is characterized by a collection of interdependent disorders, including abdominal obesity, dyslipidemia, hyperglycemia, hypertension, and diabetes. The current study aimed to estimate the prevalence of MS in Qom, Iran. MATERIALS AND METHODS: A population-based screening program was conducted in the city of Qom, in 845 urban adult men over 25 years old in 2014. Abdominal obesity, fasting blood glucose (FBG), blood pressure, and the serum lipid profile were measured in subjects after fasting for at least 8 hours. MS was defined according to the Adult Treatment Panel III criteria. Data were analyzed using the chi-square test, t-test, and multiple logistic regression. RESULTS: The overall prevalence of MS was 23.0%, and the most common prevalent metabolic abnormalities associated with MS were low high-density lipoprotein cholesterol (< 40 mg/dL) in 34.3% of subjects, a waist circumference >102 cm in 33.9%, blood pressure ≥130/85 mmHg in 27.6%, fasting triglycerides (TG) ≥150 mg/dL in 25%, and FBG ≥110 mg/dL in 20.6%. A FBG level ≥110 mg/dL (odds ratio [OR]=4.85; 95% confidence interval [CI], 2.14~8.24), dyslipidemia (OR=3.51; 95% CI, 2.10~5.89), and a fasting TG ≥150 mg/dL were the most important factors contributing to MS. CONCLUSIONS: The prevalence of MS in men in Qom was higher than has been reported in other countries, but it was lower than the mean values that have been reported elsewhere in Iran. FBG was the most important factor contributing to MS, and all elements of the lipid profile showed important associations with MS.
Adult ; Blood Glucose ; Blood Pressure ; Cholesterol ; Dyslipidemias ; Fasting ; Humans ; Hyperglycemia ; Hyperlipidemias ; Hypertension ; Iran ; Lipid Metabolism Disorders ; Lipoproteins ; Logistic Models ; Male ; Mass Screening ; Obesity, Abdominal ; Prevalence ; Triglycerides ; Waist Circumference

OBJECTIVETo study the effects of recombinant human growth hormone (r-hGH) replacement therapy on glucose and lipid metabolism and thyroid function in children with idiopathic short stature (ISS).

METHODSForty-seven ISS children with a mean age of 10±3 years treated between January 2009 and January 2013 were enrolled. All children underwent r-hGH replacement therapy for 3-24 months and were followed up once every 3 months. Fasting blood glucose (FBG), insulin (INS), blood lipids and thyroid function were measured before treatment and after 0-1 and 1-2 years of treatment.

RESULTSAfter treatment with r-hGH, there were no significant changes in FBG, INS, insulin sensitivity index (ISI), and FBG/INS ratio (FGIR), but the FGIR showed a declining trend. The percentage of patients with FGIR<7 (a marker of insulin resistance) was 13% before treatment compared to 18% 1-2 years after treatment. The atherosclerosis index decreased after r-hGH treatment, but there were no significant changes in total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and BMI. Furthermore, no significant change in thyroid function was observed after r-hGH therapy.

CONCLUSIONSr-hGH therapy can improve lipid metabolism, without significant impacts on thyroid function, FBG and INS. It seems to be a safe and reliable therapy for children with ISS. However, this therapy possibly reduces insulin sensitivity.

Adolescent ; Blood Glucose ; analysis ; Child ; Child, Preschool ; Female ; Glucose ; metabolism ; Growth Disorders ; drug therapy ; physiopathology ; Hormone Replacement Therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Insulin ; blood ; Lipid Metabolism ; drug effects ; Male ; Thyroid Gland ; drug effects ; physiopathology

OBJECTIVETo observe the features of lipid metabolism disorders of peritoneal dialysis(PD)patients and hemodialysis(HD)patients and explore the association of lipid metabolism disorder with peritoneum transport ability and mortality.

METHODSThe clinical data of 127 PD patients and 95 HD patients who had received regular dialysis for more than 3 months in Peking Union Medical College Hospital since March 2009 were retrospectively analyzed.Serum lipid profiles were tested.Serum hypersensitive C reactive protein(hsCRP)was examined by immune turbidimetric method.Serum carbohydrate antigen 125(CA125)and iPTH were detected by electrochemical luminescence method.Peritoneum transport ability was evaluated through peritoneal equilibration test(PET).After a 2-year follow-up,the levels of CA125 and the peritoneum transport abilities were compared between the baseline data and the end point,and the relationship between lipid disorder and the mortality was analyzed.

RESULTSAfter the 2-year follow-up,25(19.7%)PD patients died.The leading cause of death was congestive heart failure(56.0%),followed by myocardial infarction(12.0%),septic shock(12.0%),respiratory failure(8.0%),asphyxiation(8.0%),and gastrointestinal bleeding(4.0%).Compared with the survivors,the death patients were older(P=0.005),with significant lower albumin level(P=0.000)and pre-albumin level(P=0.001).However,there was no significant difference in other clinical features including body mass index(BMI),blood pressure,dialysis time,nPCR,iPTH,hemoglobin,hsCRP,and serum lipid level(all P>0.05).COX regression analysis showed that diabetes mellitus(P=0.030)and mean SBP(P=0.048)were significantly associated with the mortality of PD patients.At the baseline,the CA125 level in patients with high,high average,and low average transport status of peritoneum was(38.02±64.37),(21.21±19.41),and(17.55±23.2)U/ml,respectively(P=0.09).There was no association between the transport status and lipid(TC,TG and LDL).

CONCLUSIONSCongestive heart failure is the leading cause of death among PD patients.Diabetes and blood pressure are the dependent risk factors of mortality.Lipid disorder is associated with CA125,while its association with peritoneum transport ability or mortality was not found.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; C-Reactive Protein ; metabolism ; Cause of Death ; Female ; Hemodiafiltration ; mortality ; Humans ; Lipid Metabolism Disorders ; mortality ; Male ; Middle Aged ; Peritoneal Dialysis ; mortality ; Peritoneum ; metabolism ; physiopathology ; Risk Factors ; Young Adult

OBJECTIVETo investigate the role of the host-encoded silent information regulator 1 (SIRT1) on hepatocytes' lipid metabolism under conditions of hepatitis C virus (HCV) infection and assess its potential effects on virus replication in vitro.

METHODSThe Huh-7.5 human hepatocyte cell line was used as the control group and Huh-7.5 cells stably expressing the HCV replicon (Huh7.5-HCV) were used as the experimental group. Effects of interferon (IFN) treatment and activation of SIRT1 by resveratrol were also observed. The mRNA and protein expression levels of SIRT1 were detected by real time (q)PCR and western blotting. Effects on SIRT1 protein activity were tested by measuring the levels of reactive oxygen species (ROS) and the nicotinamide adenine dinucleotide (NAD+)/beta-nicotinamide adenine dinucleotide, reduced (NADH) by flow cytometry and chromatometry, and the levels of triacylglycerol (TG), total cholesterol (TC), and fatty acid beta oxidation rate by enzymatic analysis and liquid scintillation counting. Effects on mRNA expression of SIRT1 downstream lipid-metabolism genes were measured by qPCR.

RESULTSThe Huh7.5-HCV cells had a significantly higher level of ROS (3.8+/-0.5 vs. Huh-7.5: 1.0+/-0.2; t = 12.736, P less than 0.01) but significantly lower levels of NAD+/NADH (0.03+/-0.01 vs. 0.12+/-0.03; t = 6.971, P less than 0.01), SIRT1 activity (0.3+/-0.1 vs. 1.0+/-0.2, 0.9+/-0.2, F = 6.766, P less than 0.01), SIRT1 mRNA (0.4+/-0.1 vs. 1.0+/-0.3, 0.9+/-0.2, F = 5.864, P less than 0.01), and SIRT1 protein (0.3+/-0.1 vs. 0.8+/-0.2, 0.9+/-0.2, F = 5.419, P less than 0.01). The lower levels of SIRT1 in Huh7.5-HCV cells accompanied decreased phosphorylation of the forkhead box O1 (FoxO1), which not only up-regulated the downstream genes of SREBP-1c, FAS, ACC, SREBP-2, HMGR and HMGS (which increased fatty acid synthesis) but also down-regulated the downstream genes of PPAR and CPT1A genes (which decreased fatty acid beta oxidation). IFN treatment restored all of the aforementioned changes. Resveratrol-induced SIRT activation improved the perturbations in lipid metabolism pathways, as evidenced by an increase in fatty acid beta oxidation and a decrease in TG and TC synthesis, as well as inhibited HCV replication.

CONCLUSIONHCV may decrease the NAD+/NADH ratio in hepatocytes, leading to a down-regulation of SIRT1 activity and expression and perturbing the downstream expression profile of lipid metabolism-related factors, ultimately causing lipid metabolism disorders and establishing a permissive intracellular environment for HCV replication.

Cell Line ; Hepacivirus ; physiology ; Hepatocytes ; metabolism ; virology ; Humans ; Lipid Metabolism Disorders ; etiology ; metabolism ; Sirtuin 1 ; metabolism ; Triglycerides ; metabolism ; Virus Replication