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1.
J Cell Sci ; 135(5)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33912961

RESUMO

Septins colocalize with membrane sterol-rich regions and facilitate recruitment of cell wall synthases during wall remodeling. We show that null mutants missing an Aspergillus nidulans core septin present in hexamers and octamers (ΔaspAcdc11, ΔaspBcdc3 or ΔaspCcdc12) are sensitive to multiple cell wall-disturbing agents that activate the cell wall integrity MAPK pathway. The null mutant missing the octamer-exclusive core septin (ΔaspDcdc10) showed similar sensitivity, but only to a single cell wall-disturbing agent and the null mutant missing the noncore septin (ΔaspE) showed only very mild sensitivity to a different single agent. Core septin mutants showed changes in wall polysaccharide composition and chitin synthase localization. Mutants missing any of the five septins resisted ergosterol-disrupting agents. Hexamer mutants showed increased sensitivity to sphingolipid-disrupting agents. Core septins mislocalized after treatment with sphingolipid-disrupting agents, but not after ergosterol-disrupting agents. Our data suggest that the core septins are involved in cell wall integrity signaling, that all five septins are involved in monitoring ergosterol metabolism, that the hexamer septins are required for sphingolipid metabolism and that septins require sphingolipids to coordinate the cell wall integrity response.


Assuntos
Aspergillus nidulans , Septinas , Aspergillus nidulans/metabolismo , Parede Celular/metabolismo , Metabolismo dos Lipídeos , Septinas/genética , Septinas/metabolismo , Esfingolipídeos/metabolismo
2.
BMC Plant Biol ; 21(1): 404, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488625

RESUMO

BACKGROUND: Brassica carinata (A) Braun has recently gained increased attention across the world as a sustainable biofuel crop. B. carinata is grown as a summer crop in many regions where high temperature is a significant stress during the growing season. However, little research has been conducted to understand the mechanisms through which this crop responds to high temperatures. Understanding traits that improve the high-temperature adaption of this crop is essential for developing heat-tolerant varieties. This study investigated lipid remodeling in B. carinata in response to high-temperature stress. A commercial cultivar, Avanza 641, was grown under sunlit-controlled environmental conditions in Soil-Plant-Atmosphere-Research (SPAR) chambers under optimal temperature (OT; 23/15°C) conditions. At eight days after sowing, plants were exposed to one of the three temperature treatments [OT, high-temperature treatment-1 (HT-1; 33/25°C), and high-temperature treatment-2 (HT-2; 38/30°C)]. The temperature treatment period lasted until the final harvest at 84 days after sowing. Leaf samples were collected at 74 days after sowing to profile lipids using electrospray-ionization triple quadrupole mass spectrometry. RESULTS: Temperature treatment significantly affected the growth and development of Avanza 641. Both high-temperature treatments caused alterations in the leaf lipidome. The alterations were primarily manifested in terms of decreases in unsaturation levels of membrane lipids, which was a cumulative effect of lipid remodeling. The decline in unsaturation index was driven by (a) decreases in lipids that contain the highly unsaturated linolenic (18:3) acid and (b) increases in lipids containing less unsaturated fatty acids such as oleic (18:1) and linoleic (18:2) acids and/or saturated fatty acids such as palmitic (16:0) acid. A third mechanism that likely contributed to lowering unsaturation levels, particularly for chloroplast membrane lipids, is a shift toward lipids made by the eukaryotic pathway and the channeling of eukaryotic pathway-derived glycerolipids that are composed of less unsaturated fatty acids into chloroplasts. CONCLUSIONS: The lipid alterations appear to be acclimation mechanisms to maintain optimal membrane fluidity under high-temperature conditions. The lipid-related mechanisms contributing to heat stress response as identified in this study could be utilized to develop biomarkers for heat tolerance and ultimately heat-tolerant varieties.


Assuntos
Brassica/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Folhas de Planta/metabolismo , Estresse Fisiológico , Temperatura Alta
3.
Nat Commun ; 12(1): 5214, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471131

RESUMO

Dyslipidemia and resulting lipotoxicity are pathologic signatures of metabolic syndrome and type 2 diabetes. Excess lipid causes cell dysfunction and induces cell death through pleiotropic mechanisms that link to oxidative stress. However, pathways that regulate the response to metabolic stress are not well understood. Herein, we show that disruption of the box H/ACA SNORA73 small nucleolar RNAs encoded within the small nucleolar RNA hosting gene 3 (Snhg3) causes resistance to lipid-induced cell death and general oxidative stress in cultured cells. This protection from metabolic stress is associated with broad reprogramming of oxidative metabolism that is dependent on the mammalian target of rapamycin signaling axis. Furthermore, we show that knockdown of SNORA73 in vivo protects against hepatic steatosis and lipid-induced oxidative stress and inflammation. Our findings demonstrate a role for SNORA73 in the regulation of metabolism and lipotoxicity.


Assuntos
Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Substâncias Protetoras/farmacologia , RNA Nucleolar Pequeno/metabolismo , Animais , Células CHO , Morte Celular/efeitos dos fármacos , Cricetulus , Diabetes Mellitus Tipo 2/metabolismo , Fígado Gorduroso/genética , Homeostase , Inflamação , Metabolismo dos Lipídeos , Lipídeos/farmacologia , Masculino , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , RNA Longo não Codificante , RNA Nucleolar Pequeno/genética , Transdução de Sinais/efeitos dos fármacos
4.
Zhonghua Gan Zang Bing Za Zhi ; 29(8): 807-811, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34517466

RESUMO

Non-alcoholic fatty liver disease has now become a common hepatic metabolic disease, but there is no universally approved therapeutic drug on the market, so there is an urgent need to explore relevant therapeutic drugs. Several studies have shown that the thyroid hormone receptor ß, which is specifically expressed in the liver, plays an important role in lipid metabolism. T3 analogs and thyroid hormone receptor ß-specific agonists have been developed for thyroid hormone receptor ß. Many studies have shown that it can inhibit hepatic triglyceride synthesis, increase hepatic cholesterol clearance, reduce lipid deposition, and at the same time partly increase insulin sensitivity, promote glucose metabolism, and improve inflammation. Therefore, it has become a therapeutic drug with great potential for the treatment of non-alcoholic fatty liver disease. Herein, the mechanism, clinical research and drug development status are reviewed in order to provide new ideas for targeted therapy of non-alcoholic fatty liver disease with thyroid hormone receptor ß.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Receptores beta dos Hormônios Tireóideos/genética
5.
Food Res Int ; 147: 110530, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399508

RESUMO

This study aimed to evaluate the possibility that Spirulina platensis crude polysaccharides may ameliorate the lipid and carbohydrate metabolism disorder, including obesity, hyperlipidemia, hyperglycemia, hepatic steatosis, and gut dysbiosis. The results showed Spirulina platensis crude polysaccharides could improve body weight, serum/liver lipid and carbohydrate indexes, and liver antioxidant parameters in high-sucrose and high-fat diet (HFD)-fed rats, which were accompanied by regulated liver mRNA expressions involved in lipid and carbohydrate metabolism disorder. In addition, SPLP intervention significantly decreased cecal level of propionic acid in HFD-fed rats. Notably, the SPLP could alter the relative abundance of Firmicutes, Bacteroides, Proteobacteria, and Actinobacteria at phylum levels. Based on Spearman's rank correlation coefficient, serum/liver lipid and carbohydrate profiles were found significantly positively correlated with genera Romboutsia, Allobaculum, Blautia, Phascolarctobacterium, Bifidobacterium, Coprococcus, Turicibacter, Erysipelotrichaceae_unclassified, Olsenella, Escherichia/Shigella, Coprobacillus, Lachnospiracea incertae, and Lactobacillus, but strongly negatively correlated with genera Atopostipes, Flavonifractor, Porphyromonadaceae_unclassified, Barnesiella, Oscillibacter, Paraprevotella, Jeotgalicoccus, Corynebacterium, Alloprevotella and Bacteroides. It was concluded that oral administration of SPLP could remarkably ameliorate the lipid and carbohydrate metabolism disorder and significantly modulate the intestinal microbiota in HFD-fed rats.


Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Metabolismo dos Carboidratos , Metabolismo dos Lipídeos , Lipídeos , Polissacarídeos , Ratos , Spirulina , Sacarose
6.
Food Res Int ; 147: 110560, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399537

RESUMO

As an important aquaculture shellfish, the superior taste and high nutritional value of oyster (Crassostrea gigas Thunberg) have drawn extensive attention. In this study, twenty-one free amino acids (FAAs) and six 5'-nucleotides were evaluated through stable isotope labeling-liquid chromatography coupled with tandem mass spectrometry (SIL-LC-MS/MS), and the lipid profile was explored using ultrahigh performance liquid chromatography-Q Exactive HF mass spectrometry (UHPLC-QE/MS). The adductor muscle of the oyster possessed a high level of sweetness-related amino acids (Arg, Gly and Hyp) and 5'-nucleotides. A total of 149 lipid species were detected in different tissues of oysters, including 17 triacylglycerols (TAGs), 6 diacylglycerols (DAGs), 61 phosphatidylcholines (PCs), 29 phosphatidylethanolamines (PEs), 11 lysophosphatidylcholines (LPCs), 8 lysophosphatidylethanolamines (LPEs), and 1 lysophosphatidylinositol (LPI). FAAs, 5'-nucleotides and lipid profile in the digestive gland of oysters can be divided into three stages, from November to April, May to July, and August to October. The highest proportion of umami-taste amino acids and 5'-nucleotides appeared from March to May. The highest percentage of high unsaturation degree glyceride and phospholipids appeared in August and April, respectively. Thus, the results reported in this study are important for product development and sustainable exploitation in the future.


Assuntos
Crassostrea , Aminoácidos , Animais , Cromatografia Líquida , Metabolismo dos Lipídeos , Nucleotídeos , Estações do Ano , Espectrometria de Massas em Tandem
7.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 365-370, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374255

RESUMO

Objective: To study the effects of electroacupuncture on the expressions of autophagy-related factors LC3-Ⅱ, Beclin1, Atg7, and P62 in the liver of rapidly aging (senescence accelerated mouse/prone8,SAMP8) mice, and to explore the mechanisms of electroacupuncture to improve liver lipid metabolism in mice. Methods: Thirty-week-old male SAMP8 mice were randomly divided into model group, drug group, and electroacupuncture group, with 7 mice in each group. Seven anti-rapid aging SAMR1 mice of the same age were used as the control group. The animals in the control group and the model group were bred routinely for 2 weeks without any intervention; the drug group was treated with intraperitoneal injection of rapamycin at the dose of 10 mg·kg-1·d-1, once a day, 6 consecutive days a week; the electroacupuncture group was given "Shenshu" and "Taichong" Electroacupuncture at point(15 minutes a day, 6 consecutive days a week). The serum lipid metabolism and liver lipid deposition of mice were detected, the distribution of liver autophagy body, the protein and mRNA expressions of liver LC3 - Ⅱ, Beclin1, Atg7 and P62 were determined. Results: Compared with the control group, the total cholesterol (TC), triglycerides (TG), and low density lipoprotein (LDL) of the model group were increased significantly(P<0.01). In the model group, lipid droplet deposition was obvious, autophagosomes were decreased, the protein and mRNA expression levels of autophagy- related factors LC3-Ⅱ, Beclin1 and Atg7 were decreased significantly (P<0.01), while the protein and mRNA expressions of P62 were increased significantly (P<0.01). Compared with the model group, the serum contents of TG, TC, and LDL of the mice in the electroacupuncture group and the drug group were decreased significantly (P<0.01), lipid droplet deposition was reduced, autophagosomes were increased, the protein and mRNA expression levels of LC3 -Ⅱ, Beclin1 and Atg7 were increased significantly(P<0.01), and the protein and mRNA expression levels of P62 were decreased significantly(P<0.01). The protein and mRNA expression levels of Beclin1 and Atg7 in the liver of the electroacupuncture group were not significantly different from the drug group (P>0.05). Conclusion: Electroacupuncture can alleviate liver lipid metabolism disorders, which may be related to the regulation of the expressions of liver autophagy related factors LC3-Ⅱ, Beclin1, Atg7, and P62, thereby promoting liver autophagy in SAMP8 mice.


Assuntos
Eletroacupuntura , Envelhecimento , Animais , Autofagia , Metabolismo dos Lipídeos , Lipídeos , Fígado , Masculino , Camundongos
8.
Nutrients ; 13(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34371841

RESUMO

Excessive liver lipid deposition is a vital risk factor for the development of many diseases. Here, we fed Sprague-Dawley rats with a control or α-lipoic acid-supplemented diet (0.2%) for 5 weeks to elucidate the effects of α-lipoic acid on preventive ability, hepatic lipid metabolism-related gene expression, and the involved regulatory mechanisms. In the current study, α-lipoic acid supplementation lowered plasma triglyceride level and hepatic triglyceride content. Reduced hepatic lipid deposition was closely associated with inhibiting fatty acid-binding protein 1 and fatty acid synthase expression, as well as increasing phosphorylated hormone-sensitive lipase expression at the protein level in α-lipoic acid-exposed rats. Hepatic miRNA sequencing revealed increased expression of miR-3548 targeting the 3'untranslated region of Fasn mRNA, and the direct regulatory link between miRNA-3548 and FASN was verified by dual-luciferase reporter assay. Taken together, α-lipoic acid lowered hepatic lipid accumulation, which involved changes in miRNA-mediated lipogenic genes.


Assuntos
Suplementos Nutricionais , Ácido Graxo Sintase Tipo I/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , MicroRNAs/metabolismo , Ácido Tióctico/farmacologia , Animais , Ácido Graxo Sintases/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Expressão Gênica/efeitos dos fármacos , Lipogênese/genética , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
9.
Nutrients ; 13(7)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34371946

RESUMO

Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic control. Taste receptors (TAS) are located through the gastrointestinal tract, and recent studies have shown they have a relationship with metabolic disorders. The aim of this study was to analyze the jejunal expression of TAS1R2, TAS1R3, TAS2R14 and TAS2R38 in women with morbid obesity, first classified according to metabolic syndrome presence (MetS; n = 24) or absence (non-MetS; n = 45) and then classified according to hepatic histology as normal liver (n = 28) or nonalcoholic fatty liver disease (n = 41). Regarding MetS, we found decreased expression of TAS2R14 in MetS patients. However, when we subclassified patients according to liver histology, we did not find differences between groups. We found negative correlations between glucose levels, triglycerides and MetS with TAS1R3 expression. Moreover, TAS2R14 jejunal expression correlated negatively with the presence of MetS and ghrelin levels and positively with the jejunal Toll-like receptor (TLR)4, peroxisome proliferator-activated receptor (PPAR)-γ, and interleukin (IL)-10 levels. Furthermore, TAS2R38 expression correlated negatively with TLR9 jejunal expression and IL-6 levels and positively with TLR4 levels. Our findings suggest that metabolic dysfunctions such as MetS trigger downregulation of the intestinal TASs. Therefore, taste receptors modulation could be a possible therapeutic target for metabolic disorders.


Assuntos
Jejuno/metabolismo , Obesidade Mórbida/genética , Receptores Acoplados a Proteínas G/genética , Paladar , Regulação para Baixo , Feminino , Expressão Gênica , Humanos , Metabolismo dos Lipídeos/genética , Fígado/patologia , Síndrome Metabólica/complicações , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/patologia , Receptores Acoplados a Proteínas G/metabolismo
10.
Nutrients ; 13(7)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34371959

RESUMO

Polycystic ovary syndrome (PCOS) increases type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) with insulin resistance. We hypothesized that a 35 g whey preload would improve insulin sensitivity and glucose handling while reducing biomarkers associated with NAFLD. Twenty-nine age-matched women (CON = 15, PCOS = 14) completed oral glycemic tolerance tests following baseline (Day 0) as well as an acute (Day 1) and short-term whey supplementation (Day 7). Whey had an interaction effect on glucose (p = 0.02) and insulin (p = 0.03), with glucose remaining stable and insulin increasing with whey supplementation. Insulin sensitivity (p < 0.01) improved with whey associated with increased glucagon secretion (p < 0.01). Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) remained unchanged, but "day" had an effect on the AST:ALT ratio (p = 0.04), whereas triglycerides and sex hormone binding globulin overall were greater in the PCOS group (p < 0.05). Total cholesterol decreased in PCOS (by 13%) and CON (by 8%) (NS). HepG2 cells treated with plasma from participants before and after whey decreased lipid accumulation in the PCOS group after whey (p < 0.05). Whey provided an insulinogenic and glycemic homeostatic effect in women with PCOS with the potential to combat NAFLD-consequences.


Assuntos
Glicemia/análise , Suplementos Nutricionais , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Proteínas do Soro do Leite/administração & dosagem , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Colesterol/sangue , Feminino , Células Hep G2 , Humanos , Insulina/sangue , Resistência à Insulina , Metabolismo dos Lipídeos , Síndrome do Ovário Policístico/metabolismo , Globulina de Ligação a Hormônio Sexual/metabolismo , Triglicerídeos/sangue , Adulto Jovem
11.
J Insect Sci ; 21(4)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34415303

RESUMO

The gut microbiota of insects usually plays an important role in the development and reproduction of their hosts. The fecundity of Henosepilachna vigintioctopunctata (Fabricius) varies greatly when they develop on different host plants. Whether and how the gut microbiota regulates the fecundity of H. vigintioctopunctata was unknown. To address this question, we used 16S rRNA sequencing to analyze the gut microbiomes of H. vigintioctopunctata adults fed on two host plant species (Solanum nigrum and Solanum melongena) and one artificial diet. The development of the ovaries and testes was also examined. Our results revealed that the diversity and abundance of gut microorganisms varied significantly in insects reared on different diets. The gut microbiota of H. vigintioctopunctata raised on the two host plants was similar, with Proteobacteria being the dominant phylum in both groups, whereas Firmicutes was the dominant phylum in the group reared on the artificial diet. The predominant microbiota in the S. nigrum group were Acinetobacter soli and Acinetobacter ursingii (Acinetobacter, Moraxellaceae); Moraxella osloensis (Enhydrobacter, Moraxellaceae); and Empedobacter brevis (Empedobacter, Weeksellaceae). The microbiota in this group are associated with high lipid metabolism. In addition, the beetles' ovaries and testes were more highly developed in the S. nigrum group than in the other two groups. These findings provide valuable information for elucidating the complex roles the gut microbiota play in the fecundity of H. vigintioctopunctata, and may also contribute to developing future novel control strategies involving this economically important pest.


Assuntos
Besouros , Fertilidade , Microbioma Gastrointestinal/genética , Animais , Bactérias/isolamento & purificação , Besouros/microbiologia , Besouros/fisiologia , DNA Bacteriano , Dieta , Feminino , Metabolismo dos Lipídeos , Masculino , Metagenômica , Ovário/crescimento & desenvolvimento , Controle de Pragas , RNA Ribossômico 16S , Testículo/crescimento & desenvolvimento
12.
Nat Commun ; 12(1): 5103, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429409

RESUMO

Hypercholesterolemia and dyslipidemia are associated with an increased risk for many cancer types and with poor outcomes in patients with established disease. Whereas the mechanisms by which this occurs are multifactorial we determine that chronic exposure of cells to 27-hydroxycholesterol (27HC), an abundant circulating cholesterol metabolite, selects for cells that exhibit increased cellular uptake and/or lipid biosynthesis. These cells exhibit substantially increased tumorigenic and metastatic capacity. Notably, the metabolic stress imposed upon cells by the accumulated lipids requires sustained expression of GPX4, a negative regulator of ferroptotic cell death. We show that resistance to ferroptosis is a feature of metastatic cells and further demonstrate that GPX4 knockdown attenuates the enhanced tumorigenic and metastatic activity of 27HC resistant cells. These findings highlight the general importance of ferroptosis in tumor growth and metastasis and suggest that dyslipidemia/hypercholesterolemia impacts cancer pathogenesis by selecting for cells that are resistant to ferroptotic cell death.


Assuntos
Colesterol/metabolismo , Ferroptose/fisiologia , Homeostase , Metabolismo dos Lipídeos , Neoplasias/metabolismo , Animais , Neoplasias da Mama , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Glutationa Peroxidase/metabolismo , Humanos , Hidroxicolesteróis , Neoplasias Pulmonares , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Metástase Neoplásica , Neoplasias/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Molecules ; 26(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34443619

RESUMO

This study was designed to investigate the influence of dietary chitosan feeding-duration on glucose and lipid metabolism in diabetic rats induced by streptozotocin and nicotinamide [a non-insulin-dependent diabetes mellitus (NIDDM) model]. Male Sprague-Dawley rats were used as experimental animals and divided into short-term (6 weeks) and long-term (11 weeks) feeding durations, and each duration contained five groups: (1) control, (2) control + 5% chitosan, (3) diabetes, (4) diabetes + 0.8 mg/kg rosiglitazone (a positive control), and (5) diabetes + 5% chitosan. Whether the chitosan feeding was for 6 or 11 weeks, the chitosan supplementation decreased blood glucose and lipids levels and liver lipid accumulation. However, chitosan supplementation decreased plasma tumor necrosis factor (TNF)-α, insulin levels, alanine aminotransferase (ALT) activity, insulin resistance (HOMA-IR), and adipose tissue lipoprotein lipase activity. Meanwhile, it increased plasma high-density lipoproteins (HDL)-cholesterol level, plasma angiopoietin-like-4 protein expression, and plasma triglyceride levels (at 11-week feeding duration only). Taken together, 11-week (long-term) chitosan feeding may help to ameliorate the glucose and lipid metabolism in a NIDDM diabetic rat model.


Assuntos
Quitosana/farmacologia , Diabetes Mellitus Experimental/metabolismo , Carboidratos da Dieta/farmacologia , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
14.
Medicine (Baltimore) ; 100(33): e26946, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414956

RESUMO

ABSTRACT: This study aimed to investigate the association between serum uric acid (SUA) level and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2DM).T2DM patients hospitalized in the Department of Hepatology, Yantai Qishan Hospital, between April 2012 and December 2018 were classified into the NAFLD group and the non-NAFLD group. Clinical data, glucose and lipid metabolism biomarkers, and liver and kidney function parameters were retrospectively collected.Five hundred eighty-three T2DM patients met the inclusion and exclusion criteria; 227 patients were included in the non-NAFLD group and 356 patients were included in the NAFLD group. Multiple linear regression analyses showed that SUA was positively correlated with body mass index (P = .003), triglycerides (P = .009), aspartate aminotransferase (P = .036), and alanine aminotransferase (P = .038) and negatively correlated with estimated glomerular filtration rate (P < .001) in T2DM patients. Multivariate regression analyses demonstrated that after adjusting for confounding factors, the SUA tertile was still significantly associated with NAFLD occurrence in T2DM patients (P for trend = .008). With reference to SUA tertile I, the odds ratios for NAFLD in the SUA tertile II and tertile III groups were 1.729 (95% confidence interval [CI]: 1.086-2.753) and 2.315 (95% CI: 1.272-4.213), respectively.The level of SUA in T2DM patients was associated with the occurrence of NAFLD. Elevated SUA was associated with a significantly increased prevalence of NAFLD. The SUA level was an independent risk factor for NAFLD occurrence in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Ácido Úrico/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Taxa de Filtração Glomerular , Humanos , Metabolismo dos Lipídeos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Fatores de Risco
15.
Environ Pollut ; 286: 117570, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438493

RESUMO

In recent years, the incidence of lipid metabolism disorders in adolescents has gradually increased, and the effects of DEHP on lipid metabolism have received widespread attention. In this study, 463 adolescents aged 16-19 years were enrolled as subjects. This study analyzed the associations between the urinary levels of DEHP metabolites (MEHP, MEOHP, MEHHP, MECPP, MCMHP, and ∑DEHP) and BMI, WHR, WtHR, VAI, LAP, the plasma levels of lipids (TC, TG, HDL-C, and LDL-C), and the peripheral blood leukocyte mRNA levels of SREBP-2, SR-BI, LDLR, and NR1H3. Animal experiments were performed to confirm and expand findings. Wistar rats were administered DEHP at 0, 5, 50, and 500 mg/kg/d for 8 weeks. The serum and liver levels of TC, TG, HDL-C, and LDL-C, and the liver mRNA and protein levels of SREBP-2, SR-BI, LDLR, and NR1H3 were measured. The results showed that WHR, VAI, and LAP were significantly positively associated with the urinary levels of MECPP and ∑DEHP; the plasma HDL-C level was significantly negatively associated with the levels of MECPP, MCMHP and ∑DEHP; the peripheral blood leukocyte mRNA levels of SREBP-2, NR1H3, and LDLR were significantly positively correlated with the MCMHP level; and the SR-BI mRNA level was significantly positively correlated with the levels of MECPP and MCMHP in adolescents. Moreover, the results of animal experiments showed that DEHP exposure significantly increased the serum levels of TC, HDL-C, and LDL-C in 500 mg/kg/d group, as well as the liver levels of TC and HDL-C, up-regulated SREBP-2 mRNA and protein expression in 50 and 500 mg/kg/d groups. DEHP exposure significantly down-regulated SR-BI and NR1H3 protein expression in the liver of the 500 mg/kg/d group rats. Our findings indicate that DEHP exposure can affect lipid metabolism in adolescents by regulating the expression of lipid metabolism-related genes.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Adolescente , Animais , Dietilexilftalato/toxicidade , Exposição Ambiental , Humanos , Metabolismo dos Lipídeos , Ratos , Ratos Wistar
16.
Int J Mol Sci ; 22(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34360681

RESUMO

The function and regulation of lipid metabolic genes are essential for plant male reproduction. However, expression regulation of lipid metabolic genic male sterility (GMS) genes by noncoding RNAs is largely unclear. Here, we systematically predicted the microRNA regulators of 34 maize white brown complex members in ATP-binding cassette transporter G subfamily (WBC/ABCG) genes using transcriptome analysis. Results indicate that the ZmABCG26 transcript was predicted to be targeted by zma-miR164h-5p, and their expression levels were negatively correlated in maize B73 and Oh43 genetic backgrounds based on both transcriptome data and qRT-PCR experiments. CRISPR/Cas9-induced gene mutagenesis was performed on ZmABCG26 and another lipid metabolic gene, ZmFAR1. DNA sequencing, phenotypic, and cytological observations demonstrated that both ZmABCG26 and ZmFAR1 are GMS genes in maize. Notably, ZmABCG26 proteins are localized in the endoplasmic reticulum (ER), chloroplast/plastid, and plasma membrane. Furthermore, ZmFAR1 shows catalytic activities to three CoA substrates in vitro with the activity order of C12:0-CoA > C16:0-CoA > C18:0-CoA, and its four key amino acid sites were critical to its catalytic activities. Lipidomics analysis revealed decreased cutin amounts and increased wax contents in anthers of both zmabcg26 and zmfar1 GMS mutants. A more detailed analysis exhibited differential changes in 54 monomer contents between wild type and mutants, as well as between zmabcg26 and zmfar1. These findings will promote a deeper understanding of miRNA-regulated lipid metabolic genes and the functional diversity of lipid metabolic genes, contributing to lipid biosynthesis in maize anthers. Additionally, cosegregating molecular markers for ZmABCG26 and ZmFAR1 were developed to facilitate the breeding of male sterile lines.


Assuntos
Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Aldeído Oxirredutases/genética , Flores/metabolismo , Metabolismo dos Lipídeos , MicroRNAs/metabolismo , Zea mays/metabolismo , Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Aldeído Oxirredutases/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas , Pólen/crescimento & desenvolvimento , Pólen/metabolismo , RNA-Seq , Zea mays/genética , Zea mays/crescimento & desenvolvimento
17.
FASEB J ; 35(9): e21831, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34383982

RESUMO

The nuclear factor of activated T-cells 5 (NFAT5) is a transcriptional regulator of macrophage activation and T-cell development, which controls stabilizing responses of cells to hypertonic and biomechanical stress. In this study, we detected NFAT5 in the media layer of arteries adjacent to human arteriosclerotic plaques and analyzed its role in vascular smooth muscle cells (VSMCs) known to contribute to arteriosclerosis through the uptake of lipids and transformation into foam cells. Exposure of both human and mouse VSMCs to cholesterol stimulated the nuclear translocation of NFAT5 and increased the expression of the ATP-binding cassette transporter Abca1, required to regulate cholesterol efflux from cells. Loss of Nfat5 promoted cholesterol accumulation in these cells and inhibited the expression of genes involved in the management of oxidative stress or lipid handling, such as Sod1, Plin2, Fabp3, and Ppard. The functional relevance of these observations was subsequently investigated in mice fed a high-fat diet upon induction of a smooth muscle cell-specific genetic ablation of Nfat5 (Nfat5(SMC)-/- ). Under these conditions, Nfat5(SMC)-/- but not Nfat5fl/fl mice developed small, focal lipid-rich lesions in the aorta after 14 and 25 weeks, which were formed by intracellular lipid droplets deposited in the sub-intimal VSMCs layer. While known for being activated by external stimuli, NFAT5 was found to mediate the expression of VSMC genes associated with the handling of lipids in response to a cholesterol-rich environment. Failure of this protective function may promote the formation of lipid-laden arterial VSMCs and pro-atherogenic vascular responses.


Assuntos
Aorta/metabolismo , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fatores de Transcrição/metabolismo , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Idoso , Animais , Aterosclerose/metabolismo , Células Cultivadas , Colesterol/metabolismo , Feminino , Células Espumosas/metabolismo , Regulação da Expressão Gênica/fisiologia , Humanos , Hipercolesterolemia/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Túnica Íntima/metabolismo
18.
Ecotoxicol Environ Saf ; 223: 112615, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34385064

RESUMO

Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. However, there is little information available on the toxicity of tralopyril to aquatic organisms. In this study, the effect of TP on carbohydrate and lipid metabolism, and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. Adverse modifications in carbohydrate metabolism were observed in larvae: hexokinase (HK) activity, succinate dehydrogenase (SDH) activity, and adenosine triphosphate (ATP) content were significantly decreased; and transcript expression of genes (GK, HK1, and PCK1) was also significantly changed. Changes of TG content, FAS activity and transcript expression of genes (ACO, ehhadh, and fas) indicate that TP disrupt lipid metabolism in zebrafish larvae. The change in expression of genes (ndufs4, Sdhα, and uqcrc2) involved in the mitochondrial respiratory complexes, and genes (polg1 and tk2) involved in the mitochondrial DNA replication and transcription indicates that these adverse effects on carbohydrate and lipid metabolism are caused by mitochondrial dysfunction.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Metabolismo dos Carboidratos , Larva , Metabolismo dos Lipídeos , Mitocôndrias , Pirróis , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética
19.
Food Res Int ; 147: 110566, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399542

RESUMO

Sphingolipids (SLs) are common in all eukaryotes, prokaryotes, and viruses, and played a vital role in human health. They are involved in physiological processes, including intracellular transport, cell division, and signal transduction. However, there are limited reviews on dietary effects on endogenous SLs metabolism and further on human health. Various dietary conditions, including the SLs-enriched diet, high-fat diet, and vitamins, can change the level of endogenous SLs metabolites and even affect human health. This review systematically summarizes the main known SLs in foods concerning their variety and contents, as well as their isolation and identification approaches. Moreover, the present review discusses the role of dietary (particularly SLs-enriched diet, high-fat diet, and vitamins) in endogenous SLs metabolism, highlighting how exogenous SLs are digested and absorbed. The role of SLs family in the pathogenesis of diseases, including cancers, neurological disorders, infectious and inflammatory diseases, and cardiovascular diseases, and in recently coronavirus disease-19 outbreak was also discussed. In the post-epidemic era, we believe that the concern for health and the need for plant-based products will increase. Therefore, a need for research on the absorption and metabolism pathway of SLs (especially plant-derived SLs) and their bioavailability is necessary. Moreover, the effects of storage treatment and processing on the content and composition of SLs in food are worth exploring. Further studies should also be conducted on the dose-response of SLs on human health to support the development of SLs supplements. More importantly, new approaches, such as, making SLs based hydrogels can effectively achieve sustained release and targeted therapies.


Assuntos
COVID-19 , Esfingolipídeos , Digestão , Humanos , Metabolismo dos Lipídeos , SARS-CoV-2
20.
Int J Mol Sci ; 22(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34445217

RESUMO

Selenoprotein T (SELENOT, SelT), a thioredoxin-like enzyme, exerts an essential oxidoreductase activity in the endoplasmic reticulum. However, its precise function remains unknown. To gain more understanding of SELENOT function, a conventional global Selenot knockout (KO) mouse model was constructed for the first time using the CRISPR/Cas9 technique. Deletion of SELENOT caused male sterility, reduced size/body weight, lower fed and/or fasting blood glucose levels and lower fasting serum insulin levels, and improved blood lipid profile. Tandem mass tag (TMT) proteomics analysis was conducted to explore the differentially expressed proteins (DEPs) in the liver of male mice, revealing 60 up-regulated and 94 down-regulated DEPs in KO mice. The proteomic results were validated by western blot of three selected DEPs. The elevated expression of Glycogen [starch] synthase, liver (Gys2) is consistent with the hypoglycemic phenotype in KO mice. Furthermore, the bioinformatics analysis showed that Selenot-KO-induced DEPs were mainly related to lipid metabolism, cancer, peroxisome proliferator-activated receptor (PPAR) signaling pathway, complement and coagulation cascades, and protein digestion and absorption. Overall, these findings provide a holistic perspective into SELENOT function and novel insights into the role of SELENOT in glucose and lipid metabolism, and thus, enhance our understanding of SELENOT function.


Assuntos
Regulação da Expressão Gênica , Glucose/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Proteômica , Selenoproteínas , Animais , Glucose/genética , Hipoglicemia/genética , Hipoglicemia/metabolismo , Masculino , Camundongos , Camundongos Knockout , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Selenoproteínas/deficiência , Selenoproteínas/metabolismo , Transdução de Sinais/genética
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