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2.
Clin Transl Med ; 14(2): e1529, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38303609

RESUMO

OBJECTIVE: Our study was to elucidate the role of RNA helicase DEAD-Box Helicase 17 (DDX17) in NAFLD and to explore its underlying mechanisms. METHODS: We created hepatocyte-specific Ddx17-deficient mice aim to investigate the impact of Ddx17 on NAFLD induced by a high-fat diet (HFD) as well as methionine and choline-deficient l-amino acid diet (MCD) in adult male mice. RNA-seq and lipidomic analyses were conducted to depict the metabolic landscape, and CUT&Tag combined with chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted. RESULTS: In this work, we observed a notable increase in DDX17 expression in the livers of patients with NASH and in murine models of NASH induced by HFD or MCD. After introducing lentiviruses into hepatocyte L02 for DDX17 knockdown or overexpression, we found that lipid accumulation induced by palmitic acid/oleic acid (PAOA) in L02 cells was noticeably weakened by DDX17 knockdown but augmented by DDX17 overexpression. Furthermore, hepatocyte-specific DDX17 knockout significantly alleviated hepatic steatosis, inflammatory response and fibrosis in mice after the administration of MCD and HFD. Mechanistically, our analysis of RNA-seq and CUT&Tag results combined with ChIP and luciferase reporter assays indicated that DDX17 transcriptionally represses Cyp2c29 gene expression by cooperating with CCCTC binding factor (CTCF) and DEAD-Box Helicase 5 (DDX5). Using absolute quantitative lipidomics analysis, we identified a hepatocyte-specific DDX17 deficiency that decreased lipid accumulation and altered lipid composition in the livers of mice after MCD administration. Based on the RNA-seq analysis, our findings suggest that DDX17 could potentially have an impact on the modulation of lipid metabolism and the activation of M1 macrophages in murine NASH models. CONCLUSION: These results imply that DDX17 is involved in NASH development by promoting lipid accumulation in hepatocytes, inducing the activation of M1 macrophages, subsequent inflammatory responses and fibrosis through the transcriptional repression of Cyp2c29 in mice. Therefore, DDX17 holds promise as a potential drug target for the treatment of NASH.


Assuntos
Transtornos do Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Masculino , Camundongos , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fibrose , Expressão Gênica , Metabolismo dos Lipídeos/genética , Transtornos do Metabolismo dos Lipídeos/genética , Lipídeos , Luciferases/metabolismo , Macrófagos/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Progressão da Doença
3.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 167045, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38306800

RESUMO

Excessive hepatic lipid droplets (LDs) accumulation-induced lipid metabolism disorder contributes to the development of non-alcoholic fatty liver disease (NAFLD). Exercise is a promising therapeutic strategy for NAFLD. However, the mechanism by which exercise ameliorates NAFLD through regulating the catabolism of hepatic LDs remains unclear. In the present study, we investigated the effect of perilipin2 (PLIN2)-lysosomal acid lipase (LIPA) axis mediating exercise-triggered lipophagy in a high-fat diet (HFD)-induced NAFLD mouse model. Our results showed that exercise could reduce HFD-induced hepatic LDs accumulation and change the expression of lipolysis-related enzymes. Moreover, exercise upregulated the expression of microtubule associated protein 1 light chain 3 (LC3) and autophagy-related proteins, and downregulated sequestosome 1 (P62) expression and promoted autophagosomes formation. Interestingly, exercise downregulated PLIN2 expression, upregulated LIPA expression, and increased the activity of hepatic LIPA and serum levels of LIPA in the NAFLD mouse model. Further mechanistic studies demonstrated that adenosine monophosphate-activated protein kinase (AMPK) activator-5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) treatment significantly increased mRNA levels and protein expression of LIPA and LC3II and decreased levels of PLIN2 and P62 in palmitic acid (PA)-treated HepG2 cells. PLIN2 silencing and LIPA overexpression notably increased the mRNA level and protein expression of LC3II and decreased the mRNA level and protein expression of p62, respectively. In summary, our findings reveal novel insights into the effect of exercise on improving lipid droplet metabolism disorder in NAFLD. Enhancing the PLIN2-LIPA axis-mediated lipophagy may be one of the key mechanisms involved in NAFLD alleviation by exercise.


Assuntos
Transtornos do Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Gotículas Lipídicas/metabolismo , Autofagia , Modelos Animais de Doenças , Transtornos do Metabolismo dos Lipídeos/metabolismo , RNA Mensageiro/metabolismo
4.
Eur Rev Med Pharmacol Sci ; 28(3): 863-878, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38375694

RESUMO

OBJECTIVE: In this study, we investigated the internal relationship between the pathogenesis of diabetic kidney disease (DKD) and abnormal glucose and lipid metabolism to identify potential biomarkers for diagnosis and treatment and investigated the role of the immune microenvironment of glucose and lipid metabolism disorders in the occurrence and progression of DKD. MATERIALS AND METHODS: The chip datasets GSE104948 and GSE96804 from the Gene Expression Common Database (GEO) were merged using the "lima" and "sva" software packages in R Software (4.2.3), and the merged dataset was used as the validation set. The intersection between the differential genes of DKD and the glucose and lipid metabolism genes in the MSigDB database was identified, and a nomogram of the incidence risk of DKD was built using three machine learning methods, namely LASSO regression, support vector machine (SVM), and random forest (RF), to validate the accuracy of the prediction model. Immune scores were conducted using the unsupervised clustering method, and patients were divided into two subgroups. The two subgroups were screened for differential genes for enrichment analysis. The differential genes of patients diagnosed with DKD were clustered into two gene subgroups for co-expression analysis. In this study, we utilized the Cytoscape software to construct a network of interactions among key genes. RESULTS: Using machine learning, a diagnostic model was developed with G6PC and HSD17B14 as key factors. Enrichment analysis and immune scoring demonstrated that the development of DKD was related to the imbalance in the microenvironment brought about by glucose lipid metabolism disorders. CONCLUSIONS: G6PC and HSD17B14 may be potential biomarkers for DKD, and the established predictive model is more helpful in predicting the incidence of DKD.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Transtornos do Metabolismo dos Lipídeos , Humanos , Metabolismo dos Lipídeos , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/genética , Modelos Estatísticos , Prognóstico , Biologia Computacional , Glucose , Aprendizado de Máquina , Biomarcadores , 17-Hidroxiesteroide Desidrogenases
5.
Res Vet Sci ; 169: 105177, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38350170

RESUMO

Subclinical ketosis (SCK) in dairy cows is often misdiagnosed because it lacks clinical signs and detection indicators. However, it is highly prevalent and may transform into clinical ketosis if not treated promptly. Due to the negative energy balance, a large amount of fat is mobilized, producing NEFA that exceeds the upper limit of liver processing, which in turn leads to the disturbance of liver lipid metabolism. The silent information regulator 1 (SIRT1) is closely related to hepatic lipid metabolism disorders. Exosomes as signal transmitters, also play a role in the circulatory system. We hypothesize that the circulating exosome-mediated adenosine 5'-monophosphate (AMP)-activated protein kinase alpha (AMPKα)-SIRT1 pathway regulates lipid metabolism disorders in SCK cows. We extracted the exosomes required for the experiment from the peripheral circulating blood of non-ketotic (NK) and SCK cows. We investigated the effect of circulating exosomes on the expression levels of mRNA and protein of the AMPKα-SIRT1 pathway in non-esterified fatty acid (NEFA)-induced dairy cow primary hepatocytes using in vitro cell experiments. The results showed that circulating exosomes increased the expression levels of Lipolysis-related genes and proteins (AMPKα, SIRT1, and PGC-1α) in hepatocytes treated with 1.2 mM NEFA, and inhibited the expression of lipid synthesis-related genes and protein (SREBP-1C). The regulation of exosomes on lipid metabolism disorders caused by 1.2 mM NEFA treatment showed the same trend as for SIRT1-overexpressing adenovirus. The added exosomes could regulate NEFA-induced lipid metabolism in hepatocytes by mediating the AMPKα-SIRT1 pathway, consistent with the effect of transfected SIRT1 adenovirus.


Assuntos
Doenças dos Bovinos , Exossomos , Cetose , Transtornos do Metabolismo dos Lipídeos , Feminino , Animais , Bovinos , Metabolismo dos Lipídeos/fisiologia , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia , Ácidos Graxos não Esterificados , Exossomos/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/veterinária , Proteínas Quinases Ativadas por AMP/genética , Cetose/veterinária , Doenças dos Bovinos/metabolismo
6.
Food Funct ; 15(3): 1539-1552, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38234289

RESUMO

Currently, the health benefits of ruminant trans fatty acids (R-TFA) are still controversial. Our previous investigations indicated that R-TFA at higher dosages (1.3% and 4% E) caused disordered lipid metabolism in mice; however, through collecting R-TFA intake data in 9 provinces of China, it was suggested that, in 2021, the range of R-TFA intake for Chinese residents was about 0.053-0.307 g d-1. Based on the 2022 Nutritional Dietary Guidelines for Chinese Residents, the recommended daily energy supply from R-TFA was about 0.11%-0.15% E. However, the health effects of R-TFA at a lower dosage are still unknown; therefore, our current research aims to further explore the effects of R-TFA on health. Through in vivo experiments, it was shown that R-TFA (0.15% E) decreased body weight gain and serum cholesterol levels in C57BL/6J mice fed a high-fat diet, while it had no significant effect on mice fed a low-fat diet. Besides, hepatic histopathology analysis suggested that R-TFA (0.15% E) ameliorated the degree of hepatic steatosis and reduced intrahepatocyte lipid droplet accumulation in C57BL/6J mice fed a high-fat diet. Through lipidomics analysis, we further screened 8 potential lipid metabolites that participate in regulating the dysregulation of lipid metabolism. Finally, it was suggested that R-TFA (0.15% E) down-regulated the expression of genes related to inflammation and cholesterol synthesis while up-regulated the expression of genes related to cholesterol clearance, which might partially explain the salutary effect of R-TFA (0.15% E) in ameliorating the hepatic steatosis and improving disordered lipid metabolism in mice fed a high-fat diet. Our current research will provide a reference for the intake of R-TFA and, furthermore, give some insights into understanding the health effects of R-TFA.


Assuntos
Fígado Gorduroso , Transtornos do Metabolismo dos Lipídeos , Ácidos Graxos trans , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta , Ácidos Graxos trans/metabolismo , Ácidos Graxos trans/farmacologia , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Fígado Gorduroso/metabolismo , Colesterol , Transtornos do Metabolismo dos Lipídeos/metabolismo , Ruminantes/metabolismo
7.
J Agric Food Chem ; 72(5): 2612-2623, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38261277

RESUMO

Allergic diseases and lipid-metabolism-disorder-derived diseases are both significant public health issues. Recent studies have shown that exosomes are associated with the course of allergic diseases and are involved in lipid metabolism. In this study, exosomes derived from cow's milk allergic (CMA) mice medially loaded lesser proteins favoring cholesterol metabolism. The levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) in the serum were increased in the CMA mice, and hepatic lipid deposition was observed in the liver, but these phenomena were improved by inhibiting the exosome release. Specifically, the higher expression of the sterol regulatory element binding factor 2 (SREBP2) protein and HMGCR gene in the liver of CMA mice indicated an increase in cholesterol synthesis. NPC1L1 was also highly expressed in the small intestine of CMA mice, and fecal TC level was decreased, suggesting that the reabsorption of cholesterol was elevated. The biosynthesis of cholesterol, the reverse cholesterol transport (RCT) process, and the synthesis of bile acid in the liver were improved by inhibiting exosome release, as well as the reabsorption of cholesterol in the small intestine. This study has for the first time demonstrated the lipid metabolism disorder caused by CMA, especially the important role of exosomes in food allergies and lipid metabolism.


Assuntos
Exossomos , Transtornos do Metabolismo dos Lipídeos , Hipersensibilidade a Leite , Bovinos , Feminino , Animais , Camundongos , Camundongos Endogâmicos BALB C , Alérgenos , Colesterol , Lipídeos , Proteínas do Leite
8.
Aquat Toxicol ; 267: 106839, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38228041

RESUMO

The surfactant perfluorooctane sulfonate (PFOS) is widely produced worldwide. It is a persistent organic pollutant in the aquatic environment and poses a serious threat to aquatic organisms, as PFOS exposure can cause liver injury in a wide range of organisms. However, it is unclear whether PFOS exposure-induced hepatocellular injury in fish is associated with ROS-mediated activation of NLRP3 inflammasome. In this study, various PFOS concentrations were applied to L8824 cells, a cell line of grass carp hepatocytes. The detrimental impacts of PFOS on oxidative stress, pyroptosis, lipid metabolism, and the discharge of inflammatory factors were examined. MCC950 and N-acetylcysteine were employed to hinder the PFOS-stimulated activation of the NLRP3 inflammasome and the excessive generation of reactive oxygen species in L8824 cells, respectively. This study demonstrated that treatment with PFOS resulted in oxidative stress and activation of NLRP3 inflammasome in L8824 cells. This led to increased expression levels of indicators related to pyroptosis, accompanied by the upregulation of pro-inflammatory cytokine expression as well as downregulation of anti-inflammatory factors. In addition, following PFOS exposure, the expression levels of genes related to lipid synthesis were upregulated and lipid catabolism-related genes were downregulated. Surprisingly, both N-acetylcysteine and MCC950 interventions significantly reduced PFOS-induced L8824 cell pyroptosis and lipid metabolism disorders. In conclusion, this research demonstrated that PFOS drives NLRP3 inflammasome activation through oxidative stress induced by reactive oxygen species overload. This in turn leads to pyroptosis and lipid metabolism disorders.


Assuntos
Fluorocarbonos , Transtornos do Metabolismo dos Lipídeos , Poluentes Químicos da Água , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Metabolismo dos Lipídeos , Piroptose , Acetilcisteína/farmacologia , Poluentes Químicos da Água/toxicidade , Hepatócitos/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Lipídeos
9.
Pestic Biochem Physiol ; 198: 105739, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38225084

RESUMO

Triphenyltin (TPT) is a widely used pesticide that has a negative impact on biological health and production efficiency. In addition, TPT poses a threat to human health through the food chain and environmental pollution. However, the exact mechanism of TPT toxicity remains unclear. In this study, we investigated the hepatotoxicity of TPT and its effects on lipid metabolism using male SD rats as an animal model. Our results from HE and serum biochemical analysis suggested that TPT could damage liver structure and function, resulting in disruption of lipid metabolism. We therefore proceeded to analyze the proteomic response of rat liver tissue after 28 days of treatment with 2 mg/kg/d TPT. Our study demonstrates that TPT has a variety of effects on liver protein expression in rats. Through bioinformatic analysis, we observed significant changes in proteins related to fatty acid oxidation and synthesis due to TPT exposure. Furthermore, western blot and RT-qPCR experiments confirmed that TPT can affect lipid metabolism through the PPAR pathway. These findings suggest that TPT exposure can lead to liver damage, lipid accumulation and metabolic disorders.


Assuntos
Transtornos do Metabolismo dos Lipídeos , Metabolismo dos Lipídeos , Compostos Orgânicos de Estanho , Humanos , Ratos , Animais , Ratos Sprague-Dawley , Proteômica , Fígado
10.
BMC Pharmacol Toxicol ; 25(1): 10, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225635

RESUMO

BACKGROUND: Cantharidin (CTD), the main toxic component of Mylabris, has been extensively used for tumor treatment in recent years. CTD-induced liver toxicity has attracted significant interest in clinic. METHODS: In this study, biochemical parameters and liver pathological changes were analyzed after CTD was administered to mice by gavage. Subsequently, a lipidomic approach was used to investigate serum lipid metabolism disorders, and the mechanism underlying CTD-induced liver injury in mice was explored. RESULTS: The results showed that the levels of TC and LDL-C were significantly increased after CTD intervention. Besides, pathological results showed inflammatory cell infiltration and hepatocyte necrosis in the liver. Furthermore, lipidomics found that a total of 18 lipid metabolites were increased and 40 were decreased, including LPC(20:4), LPC(20:3), PC(22:6e/2:0), PE(14:0e/21:2), PC(18:2e/22:6), glycerophospholipids, CE(16:0), CE(18:0) Cholesterol esters and TAG(12:0/12:0/22:3), TAG(16:1/16:2/20:4), TAG(18:1/18:1/20:0), TAG(16:2/18:2/18:2), TAG(18:0/18:0/20:0), TAG(13:1/19:0/19:0) glycerolipids. Metabolic pathway analysis found that glycerophospholipid, glycerol ester and glycosylphosphatidylinositol (GPI)-anchored biosynthetic metabolic pathways were dysregulated and the increase in PE caused by glycophoric metabololism and GPI may be the source of lipid metabolism disorders caused by CTD. Overall, the present study provided new insights into the mechanism of CTD-induced liver injury and increased drug safety during clinical application.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Transtornos do Metabolismo dos Lipídeos , Camundongos , Animais , Lipidômica , Cantaridina , Metabolismo dos Lipídeos
11.
Lipids Health Dis ; 23(1): 25, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263170

RESUMO

BACKGROUND: Lipid disorders are a potent risk factor for cardiovascular diseases. Moreover, the intake of dietary fatty acids has been closely related to blood lipid levels. Therefore, this cross-sectional study examined the associations between dietary patterns related to fatty acid intake and lipid disorders in Korean adults. METHODS: From the 2013-2019 Korea National Health and Nutrition Examination Surveys data, 8399 men and 11404 women (aged ≥ 19 years) were selected. Reduced rank regression was employed to identify dietary patterns from 26 food groups, aiming to explain the maximum variation in the intake of saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), omega-3 fatty acids, and the PUFA/SFA ratio. Associations of quintiles (Q) of dietary pattern scores with lipid disorders were examined using multiple logistic regression stratified by sex. RESULTS: Three dietary patterns were identified: dietary pattern 1 showed positive factor loadings for vegetable oils, seasonings, legumes, nuts, and fish; dietary pattern 2 was high in consumption of red meat, bread and snacks, and milk and dairy products; and dietary pattern 3 was rich in fish and milk and dairy products. In men, dietary pattern 3 was inversely associated with elevated triglycerides (Q5 vs. Q1: odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.69-0.97, P-trend = 0.008). In women, dietary pattern 2 was positively associated with elevated total cholesterol (OR = 1.31, 95% CI = 1.12-1.52, P-trend < 0.001) but inversely associated with low HDL-cholesterol (OR = 0.70, 95% CI = 0.59-0.83, P-trend < 0.001). CONCLUSION: In this study, dietary patterns explaining the intake of various types of fatty acids were differentially associated with lipid disorders in Korean adults. Dietary pattern characterized by higher intakes of red meat, bread and snacks and milk and dairy products were positively associated with elevated total cholesterol, whereas dietary pattern rich in fish consumption showed an inverse association with elevated triglycerides. These findings could be instrumental in developing dietary guidelines and strategies for preventing and managing lipid disorders in this population.


Assuntos
Hipercolesterolemia , Hipertrigliceridemia , Transtornos do Metabolismo dos Lipídeos , Adulto , Animais , Masculino , Feminino , Humanos , Estudos Transversais , Leite , Ácidos Graxos , Triglicerídeos , Colesterol , República da Coreia
12.
Lipids Health Dis ; 23(1): 28, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273354

RESUMO

BACKGROUND: As independent and correctable risk factors, disturbances in lipid metabolism are significantly associated with type 2 diabetes mellitus (T2DM). This research investigated the mechanism underlying the lipid-regulating effects of Yam Gruel in diabetic rats. METHODS: First, rats in the control group were given a normal diet, and a diabetic rat model was established via the consumption of a diet that was rich in both fat and sugar for six weeks followed by the intraperitoneal injection of streptozotocin (STZ). After the model was established, the rats were divided into five distinct groups: the control group, model group, Yam Gruel (SYZ) group, metformin (MET) group, and combined group; each treatment was administered for six weeks. The fasting blood glucose (FBG), body and liver weights as well as liver index of the rats were determined. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), aspartic acid transaminase (AST), alanine aminotransferase (ALT), and nonesterified fatty acid (NEFA) levels were measured. Oil Red O staining was used to assess hepatic steatosis. In addition, the levels of Phospho-acetyl-CoA carboxylase (p-ACC), acetyl coenzyme A carboxylase (ACC), AMP-activated protein kinase (AMPK), Phospho-AMPK (p-AMPK), carnitine palmitoyl transferase I (CPT-1), and Malonyl-CoA decarboxylase (MLYCD) in liver tissues were measured by real-time PCR (q-PCR) and western blotting. RESULTS: After 6 weeks of treatment, Yam Gruel alone or in combination with metformin significantly reduced FBG level, liver weight and index. The concentrations of lipid indices (TG, TC, NEFA, and LDL-C), the levels of liver function indices (ALT and AST) and the degree of hepatic steatosis was improved in diabetic rats that were treated with Yam Gruel with or without metformin. Furthermore, Yam Gruel increased the protein levels of p-ACC/ACC, p-AMPK/AMPK, MLYCD, and CPT-1, which was consistent with the observed changes in gene expression. Additionally, the combination of these two agents was significantly more effective in upregulating the expression of AMPK pathway-related genes and proteins. CONCLUSIONS: These results demonstrated that Yam Gruel may be a potential diet therapy for improving lipid metabolism in T2DM patients and that it may exert its effects via AMPK/ACC/CPT-1 pathway activation. In some respects, the combination of Yam Gruel and metformin exerted more benefits effects than Yam Gruel alone.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Dioscorea , Fígado Gorduroso , Transtornos do Metabolismo dos Lipídeos , Metformina , Humanos , Ratos , Animais , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Dioscorea/metabolismo , Metabolismo dos Lipídeos , Metformina/farmacologia , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Ácidos Graxos não Esterificados/metabolismo , LDL-Colesterol/metabolismo , Fígado/metabolismo , Fígado Gorduroso/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Triglicerídeos/metabolismo , Dieta Hiperlipídica/efeitos adversos
13.
Obes Rev ; 25(4): e13687, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38204297

RESUMO

OBJECTIVE: This study sought to systematically compare the efficacy and mechanism of cyclodextrins as drug interventions in lipid metabolism diseases, potentially providing ideas for subsequent research directions and clinical applications. METHODS: We used the bibliometric method for feature mining, applied VOSviewer software for clustering analysis, and applied content analysis for objective descriptions and accurate analysis. RESULTS: (1) We collected more than 50 studies, which is the basic database of this study. (2) The academic bubble map showed that this research area was popular in the United States. (3) Cluster analysis showed that the intensively studied diseases in this field were Niemann-Pick type C (NPC), atherosclerosis (AS), and obesity. The hot-spot cyclodextrin types were HP-ß-CD. (4) Literature measurement revealed the involvement of 15 types of lipid metabolism diseases. Among them, NPC, diabetes, and obesity were studied in clinical trials. Dyslipidemia and AS have been reported relatively more frequently in animal experiments. The studies of cellular experiments provide insight into the molecular mechanisms that intervene in lipid metabolism diseases from multiple perspectives. The exploration of the molecular mechanisms by which cyclodextrins exert their pharmacological effects mainly revolves around lipid metabolism. CONCLUSION: It is worthwhile to investigate the role and mechanism of cyclodextrins in other lipid metabolism diseases. The potential efficacy evaluation of cyclodextrins as pharmaceutical drugs for oral or injectable formulations is less studied and may become a new focus in the future.


Assuntos
Ciclodextrinas , Transtornos do Metabolismo dos Lipídeos , Animais , Ciclodextrinas/farmacologia , Ciclodextrinas/uso terapêutico , Metabolismo dos Lipídeos , Colesterol/metabolismo , Transtornos do Metabolismo dos Lipídeos/tratamento farmacológico , Obesidade/tratamento farmacológico
14.
Food Funct ; 15(1): 110-124, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38044717

RESUMO

Increasing evidence supports the existence of fetal-originated adult diseases. Recent research indicates that the intrauterine environment affects the fetal hypothalamic energy intake center. Inulin is a probiotic that can moderate metabolic disorders, but whether maternal inulin intervention confers long-term metabolic benefits to lipid metabolism in offspring in their adult lives and the mechanism involved are unknown. Here, we used a maternal overnutrition model that was induced by excess energy intake before and during pregnancy and lactation and maternal inulin intervention was performed during pregnancy and lactation. The hypothalamic genome methylation in offspring was analyzed using a methylation array. The results showed that maternal inulin treatment modified the maternal high-fat diet (HFD)-induced increases in body weight, adipose tissue weight, and serum insulin and leptin levels and decreases in serum adiponectin levels. Maternal inulin intervention regulated the impairments in hypothalamic leptin resistance, induced the methylation of Socs3, Npy, and Il6, and inhibited the methylation of Lepr in the hypothalamus of offspring. In conclusion, maternal inulin intervention modifies offspring lipid metabolism, and the underlying mechanism involves the methylation of genes in the hypothalamus feeding circuit.


Assuntos
Transtornos do Metabolismo dos Lipídeos , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Humanos , Leptina , Dieta Hiperlipídica/efeitos adversos , Obesidade/genética , Obesidade/metabolismo , Inulina/farmacologia , Inulina/metabolismo , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Hipotálamo/metabolismo , Lipídeos , Fenômenos Fisiológicos da Nutrição Materna
15.
Toxicology ; 501: 153696, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38056589

RESUMO

Atrazine (ATR) is a widely used herbicide and due to its persistence in environment and bioaccumulation, it can cause harmful impacts on human health. ATR exposure can lead to disorders of lipid metabolism in the liver, but its underlying mechanism is still unclear. 40 eight-week-old rats were given different doses of ATR (0, 0.5, 5 and 50 mg/kg/d) for 90 days. The liver tissue and serum were collected for histological observation and biochemical analysis. The levels of lipid and oxidative stress were assessed using colorimetry. Changes in MMP and ROS of liver cells were observed through flow cytometry. The expression of mRNA and protein was detected using Real-Time PCR and western blot. The results showed that TC and HDL-C levels in both the liver and serum were increased in the ATR-treated groups. The levels of MDA were accumulated, while the levels of SOD and GSH were depleted in the liver with ATR exposure. The expression of liver lipid metabolism related genes (SCD1, DGAT2, ACC1, PPARγ) was elevated. The liver ERS was activated and the gene expression of IRE1α/XBP1 signal pathway and GRP78, GRP94 in the liver was increased. There was a correlation between the levels of ERS and the levels of lipid metabolism. These results suggested that ATR can activate ERS and promote the expression of IRE1α/XBP1 signaling pathway, and further lead to lipid metabolism disorders in rat liver. This study can provide valuable insights as a reference for the prevention and control of hazards associated with agricultural residues.


Assuntos
Atrazina , Transtornos do Metabolismo dos Lipídeos , Humanos , Ratos , Animais , Metabolismo dos Lipídeos , Endorribonucleases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Fígado/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteína 1 de Ligação a X-Box
16.
Poult Sci ; 103(1): 103251, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984004

RESUMO

The objective of this study was to investigate the preventive effects and mechanisms of genistein (GEN) on production performance and metabolic disorders in broilers under chronic heat stress (HS). A total of 120 male 3-wk-old Ross broilers were randomly assigned to 5 groups: a thermoneutral zone (TN) group maintained at normal temperature (21°C ± 1°C daily), an HS group subjected to cyclic high temperature (32°C ± 1°C for 8 h daily), and 3 groups exposed to HS with varying doses of GEN (50, 100, or 150 mg/kg diet). The experimental period lasted for 3 wk. Here, HS led to a decline in growth performance parameters and hormone secretion disorders (P < 0.05), which were improved by 100 and 150 mg/kg GEN treatment (P < 0.05). Moreover, the HS-induced increases in the liver index (P < 0.01) and abdominal fat rate (P < 0.05) were attenuated by 150 mg/kg GEN (P < 0.05). The HS-induced excessive lipid accumulation in the liver and serum (P < 0.01) was ameliorated after 100 and 150 mg/kg GEN treatment (P < 0.05). Furthermore, the HS-induced decreases in lipolysis-related mRNA levels and increases in lipid synthesis-related mRNA levels in the liver (P < 0.01) were effectively blunted after 100 and 150 mg/kg GEN treatment (P < 0.05). Importantly, the HS-stimulated hepatic mitochondrial energetic dysfunction and decreases in the mRNA or protein levels of peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A in the liver were ameliorated by 150 mg/kg GEN (P < 0.05). Moreover, 50 to 150 mg/kg GEN treatment resulted in a significant increase in the mRNA or protein levels of G protein-coupled estrogen receptor (GPR30), AMP-activated protein kinase (AMPK) α1, phosphorylated AMPKα, and phosphorylated acetyl-CoA carboxylase α. Collectively, GEN alleviated metabolic disorders and hepatic mitochondrial energetic dysfunction under HS, possibly through the activation of GPR30-AMPM-PGC-1α pathways. These data provide a sufficient basis for GEN as an additive to alleviate HS in broilers.


Assuntos
Transtornos de Estresse por Calor , Transtornos do Metabolismo dos Lipídeos , Animais , Masculino , Galinhas/fisiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Genisteína/farmacologia , Genisteína/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Resposta ao Choque Térmico , Transtornos de Estresse por Calor/tratamento farmacológico , Transtornos de Estresse por Calor/veterinária , Transdução de Sinais , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/veterinária , RNA Mensageiro/metabolismo , Lipídeos
17.
Diabetes Metab Res Rev ; 40(2): e3720, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37691570

RESUMO

OBJECTIVES: Increasing visceral fat deposition with raised prevalence of obesity and metabolic syndrome is associated with many adverse conditions, especially cardiovascular diseases and diabetes. Although there are many studies that investigate hepatic steatosis in hypothyroidism and subclinical hypothyroidism, to the best of our knowledge, there is no study investigating its relationship with pancreatic steatosis. In the present study, the purpose was to investigate this relationship. METHODS: Physical and biochemical characteristics of 30 hypothyroid, 30 subclinical hypothyroid, and 30 euthyroid volunteers were recorded in this cross-sectional study. Liver and pancreatic steatosis were evaluated with ultrasonography. RESULTS: It was found that pancreatic steatosis was increased in hypothyroid and subclinical groups when compared to the control group, and hepatic steatosis was increased in the subclinical group when compared to the control group (steatosis; p = 0.002, p = 0.004, p = 0.001, p = 0.002, p = 0.002, p = 0.004). Pancreatic steatosis was positively correlated with age, hepatic steatosis, height, weight, BMI, waist circumference, hip circumference, hemoglobin, Insulin, alanine aminotransferase, Triglyceride, Creatinine, and gamma-glutamyltransferase and was negatively correlated with total cholesterol, high-density lipoproteins. CONCLUSIONS: The prevalence of pancreatic steatosis was found to be increased in hypothyroidism and subclinical hypothyroidism when compared with the euthyroid control group.


Assuntos
Fígado Gorduroso , Hipotireoidismo , Transtornos do Metabolismo dos Lipídeos , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Pancreatopatias , Humanos , Estudos Transversais , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Obesidade , Pancreatopatias/complicações , Pancreatopatias/epidemiologia , Pâncreas/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia
18.
Environ Pollut ; 343: 123153, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38103713

RESUMO

As a potential environmental obesogen, triclosan (TCS) carries inherent risks of inducing obesity and metabolic disorders. However, the underlying molecular mechanisms behind the lipid metabolism disorder induced by TCS have remained elusive. Through a fusion of transcriptomics and microRNA target prediction, we hypothesize that miR-101a as a responsive miRNA to TCS exposure in zebrafish, playing a central role in disturbing lipid homeostasis. As an evidence, TCS exposure triggers a reduction in miR-10a expression that accompanied by elevation of genes linked to regulation of lipid homeostasis. Through precision-controlled interventions involving miRNA expression modulation, we discovered that inhibition of miR-101a enhanced expression of its target genes implicated in lipid homeostasis, subsequently triggering excessive fat accumulation. Meanwhile, the overexpression of miR-101a acts as a protective mechanism, counteracting the lipid metabolism disorder induced by TCS in the larvae. Notably, the combination of short-chain fatty acids (SCFAs) emerged as a potential remedy to alleviate TCS-induced lipid accumulation partially by counteracting the decline in miR-101a expression induced by TCS. These revelations provide insight into a prospective molecular framework underlying TCS-triggered lipid metabolism disorders, thereby paving the way for pre-emptive strategies in combating the ramifications of TCS pollution.


Assuntos
Transtornos do Metabolismo dos Lipídeos , MicroRNAs , Triclosan , Animais , Triclosan/toxicidade , Triclosan/metabolismo , Peixe-Zebra/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ácidos Graxos Voláteis/metabolismo
19.
Ecotoxicol Environ Saf ; 270: 115887, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38157803

RESUMO

Chronic noise exposure is correlated with gut microbiota dysbiosis and glucose and lipid metabolism disorders. However, evidence on the mechanisms underlying of gut microbiota alterations in chronic noise induced glucose and lipid metabolism disorders is limited, and the potential aftereffects of chronic noise exposure on metabolic disorders remain unclear. In present study, we established chronic daytime and nighttime noise exposure mice models to explore the effects and underlying mechanism of gut microbiota on chronic noise-induced glucose and lipid metabolism disorders. The results showed that exposure to chronic daytime or nighttime noise significantly increased the fasting blood glucose, serum and liver TG levels, impaired glucose tolerance, and decreased serum HDL-C levels and liver TC levels in mice. However, after 4 weeks of recovery, only serum TG of mice in nighttime noise recovery group remained elevated. Besides, exposure to chronic noise reduced the intestinal tight junction protein levels and increased intestinal permeability, while this effect did not completely dissipate even after the recovery period. Moreover, chronic noise exposure changed the gut microbiota and significantly regulated metabolites and metabolic pathways, and further activate hepatic gluconeogenesis CRTC2/CREB-PCK1 signaling pathway and lipid synthesis SREBP1/SCD signaling pathway through intestinal hepatic axis. Together, our findings demonstrated that chronic daytime and nighttime noise exposure could cause the glucose and lipid metabolism disorder by modulating the gut microbiota and serum metabolites, and activating hepatic gluconeogenic CREB/CRTC2-PCK1 signaling and lipid synthesis SREBP1/SCD signaling pathway. The potential aftereffects of noise exposure during wakefulness on metabolic disorders are more significant than that of noise exposure during sleep.


Assuntos
Microbioma Gastrointestinal , Transtornos do Metabolismo dos Lipídeos , Doenças Metabólicas , Animais , Camundongos , Metabolismo dos Lipídeos , Glucose/metabolismo , Fígado/metabolismo , Doenças Metabólicas/metabolismo , Lipídeos , Camundongos Endogâmicos C57BL
20.
Pestic Biochem Physiol ; 197: 105646, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38072521

RESUMO

Hexaconazole (Hex) is a widely used and high frequency detected triazole fungicide in agricultural products and environment which may pose potential toxicity to the nontargeted organisms. Hex had been reported to affect lipid homeostasis while the mechanism was undefined. This study aims to explore the characteristic lipidomic profiles and clarify the underlying signaling pathways of Hex-induced lipid metabolism disorder in rat liver. The results showed that sub-chronic exposure to environmental related concentrations of Hex caused histopathological changes, oxidative stress, fat accumulation, lipid biochemical parameter increase in rats. Moreover, the untargeted lipidomic analysis showed that the levels of TAG, PC, and PE and the pathway of glycerophospholipid metabolism were heavily altered by Hex. We further analyzed the lipid metabolism related genes and proteins which revealed that Hex exposure increased amount of lipogenesis by activating oxidative stress-mediated mTOR-PPAR-γ/SREBP1 signaling pathways. The imbalance of lipid homeostasis induced by Hex exposure might further lead to obesity, cardiovascular diseases (CVDs), and hyperlipidemia. Our results provided systematic and comprehensive evidence for the mechanism of Hex-induced lipid metabolism disorder at environmental concentrations and supplied a certain basis for its health risks assessment.


Assuntos
Transtornos do Metabolismo dos Lipídeos , Metabolismo dos Lipídeos , Ratos , Animais , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Estresse Oxidativo , Triazóis/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR , Lipídeos , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/patologia , Fígado/metabolismo
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