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Objective To investigate the effect and mechanism of HHQ 16, a derivative of astragaloside Ⅳ, on hepatocyte lipid accumulation. Methods Free fatty acids were used to stimulate lipid hepatocyte accumulation. Triglyceride and Oil Red O staining were detected to reflect hepatocyte lipid accumulation. The expression of α1-acidglycoprotein (ORM) and its regulators were detected by real-time quantitative PCR and immunoblotting. The expression of ORM1 was interfered with siRNA to determine whether it mediated the action of HHQ16.The expression of ORM1 was interfered by siRNA to determine whether it mediated the action of HHQ16. Results HHQ16 significantly ameliorated FFA-induced hepatocyte lipid deposition. HHQ16 elevated ORM expression, and the protective effect of HHQ16 on hepatocyte lipid accumulation was reversed by ORM interference. Conclusion HHQ16 could ameliorate hepatocyte lipid accumulation by elevating ORM.
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OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease (NAFLD) in mice. METHODS The male ApoE-/- mice were randomly divided into the model group and Hirudo low- dose and high-dose groups (0.45, 0.9 g/kg), with 10 mice in each group; another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically, once a day, for 8 consecutive weeks. In the 13th week, the body weight and liver weight of mice in each group were measured after the last medication, and the liver index was calculated; the serum levels of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF- α), interleukin-1β (IL-1β), IL-6, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected; the liver pathomorphological changes were observed; the protein expressions of peroxisome proliferator-activated receptor γ(PPARγ) and silence information regulator type 1 (SIRT1) were detected. RESULTS Compared with the control group, the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells, with significant lipid accumulation; the body weight, liver weight and liver index of the mice, and serum levels of NF-κB, TNF-α, IL-1β, IL-6, TC, TG and LDL-C significantly increased, while the serum level of HDL-C, the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased (P<0.01). Compared with the model group, the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups; the body weight, liver weight and liver index, the serum levels of NF-κB, TNF-α, IL-1β, IL-6, TC, TG and LDL-C decreased significantly, while the serum level of HDL-C, the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly (P<0.05 or P<0.01). CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1, thus having a significant ameliorative effect on NAFLD.
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【Objective】 To investigate the effect of mitochondrial unfolded protein response (UPRmt) on lipid metabolism in human kidney 2 (HK-2) cells . 【Methods】 Lipid accumulation was induced by palmitic acid (PA) in HK-2 cells. The cells were pretreated with siRNA or CDDO respectively. The intracellular lipid accumulation was observed by oil red staining; mitochondrial membrane potential (MMP) was measured by JC-1.The contents of reactive oxygen species (ROS) in mitochondria were measured by Mito-SOX, and the expressions of HSP60, LONP1, CLPP, ACOX1, PPARα, PGC1α and CPT1α were detected by Western blotting. 【Results】 PA induced lipid aggregation, MMP decrease, ROS generation in mitochondria and the decreased expression of UPRmt proteins (e. g., HSP60 and LONP1) in HK-2 cells. Pretreatment of HK-2 cells with siRNA could aggravate lipid aggregation, MMP decrease and ROS generation induced by PA, and further decrease the expression of HSP 60and LONP1.Pretreatment of HK-2 cells with CDDO alleviated lipid aggregation, MMP decrease, ROS generation and decreased HSP60 and LONP1 expressions induced by PA. 【Conclusion】 Lipid aggregation in HK-2 cells induced by PA may be related to mitochondrial dysfunction and UPRmt has a protective effect on HK-2 cells in the process.
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Fundamento: Las alteraciones del estado nutricional materno generalmente se relacionan con desviaciones del crecimiento fetal, que pueden detectarse por los parámetros biofísicos fetales e identifican la posible condición trófica al nacer. Objetivo: Determinar la posible relación entre los parámetros biométricos fetales, la condición trófica al nacer y el producto de acumulación de los lípidos. Metodología: Se realizó un estudio transversal en el Policlínico Chiqui Gómez Lubian del municipio Santa Clara, durante el año 2019, en una población de 253 gestantes normopeso supuestamente sanas al inicio de la gestación. La muestra no probabilística fue de 144 gestantes. Las variables de estudio fueron: producto de acumulación de los lípidos, biometría fetal y condición trófica al nacer. Se utilizaron métodos teóricos, empíricos y estadísticos. Resultados: En el segundo trimestre ningún parámetro biométrico coincidió con la condición al nacer de pequeño, mientras que para el grande coincidieron las circunferencias cefálica y abdominal. En el tercer trimestre la longitud del fémur y la circunferencia abdominal coinciden en la identificación del pequeño y del grande. El PAL se correlacionó con la circunferencia abdominal del tercer trimestre y con el peso al nacer; presentando mayor frecuencia de valores en el tercer tertil para los nacimientos grandes. Conclusiones: La circunferencia abdominal fue el parámetro biométrico con mayor coincidencia con la condición trófica al nacer, la que se asoció con valores en el tercer tertil del PAL para la detección de nacimientos grandes, relacionándose el fenotipo normopeso metabólicamente obeso con el crecimiento fetal por exceso.
Background: Maternal nutritional status disorders are usually related to fetal growth deviations, which can be detected by fetal biophysical parameters and identify the possible trophic condition at birth. Objective: To determine the possible relationship between fetal biometric parameters, the birth trophic state and lipid accumulation product. Methodology: A cross-sectional study was conducted at the Chiqui Gómez Lubian Polyclinic in Santa Clara municipality, during 2019, in a population of 253 normal-weight pregnant women who were apparently healthy at the beginning of their gestation. The non-probability sample was made up of 144 pregnant women. Study variables were: lipid accumulation product, fetal biometry and trophic condition at birth. Theoretical, empirical and statistical methods were used. Results: In the second trimester, none of the biometric parameters matched the condition at birth as a small child, while in the large one the head and abdominal circumferences matched. In the third trimester, femoral length and abdominal circumference coincide in identifying the small one and the large one. LAP correlated with third trimester abdominal circumference and birth weight, presenting higher frequency of values in the third tertile for large births. Conclusions: Abdominal circumference was the biometric parameter with the highest coincidence with trophic condition at birth, associated with values in the third tertile of the LAP for detecting large births, relating the metabolically obese normal weight phenotype with excessive fetal growth.
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Recién Nacido , Biometría , Edad Gestacional , Peso Fetal , Desarrollo Fetal , Producto de la Acumulación de LípidosRESUMEN
Alcoholic liver disease(ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Methyl ferulic acid(MFA) has been proven to significantly inhibit alcohol-induced lipid production in L02 cells through the AMP-activated protein kinase(AMPK) pathway, but its in-depth mechanism remains unclear. This study aimed to further clarify the mechanism of MFA in improving lipid accumulation in L02 cells through the microRNA-378b(miR-378b)-mediated calcium/calmodulin-dependent protein kinase kinase 2(CaMKK2)-AMPK signaling pathway based on existing researches. L02 cells were induced by 100 mmol·L~(-1) ethanol for 48 h to establish the model of ALD in vitro, and 100, 50, and 25 μmol·L~(-1) concentration of MFA was treated. MiR-378b plasmids(containing the overexpression plasmid-miR-378b mimics, silence plasmid-miR-378b inhibitor, and their respective negative control-miR-378b NCs) were transfected into L02 cells by electroporation to up-regulate or down-regulate the levels of miR-378b in L02 cells. The levels of total cholesterol(TC) and triglyceride(TG) in cells were detected by commercial diagnostic kits and automatic biochemical analyzers. The expression levels of miR-378b in L02 cells were detected by real-time quantitative polymerase chain reaction(qRT-PCR). CaMKK2 mRNA levels were detected by PCR, and protein expressions of related factors involved in lipid synthesis, decomposition, and transport in lipid metabolism were detected by Western blot. The results displayed that ethanol significantly increased TG and TC levels in L02 cells, while MFA decreased TG and TC levels. Ethanol up-regulated the miR-378b level, while MFA effectively inhibited the miR-378b level. The overexpression of miR-378b led to lipid accumulation in ethanol-induced L02 cells, while the silence of miR-378b improved the lipid deposition induced by ethanol. MFA activated the CaMKK2-AMPK signaling pathway by lowering miR-378b, thus improving lipid synthesis, decomposition, and transport, which improved lipid deposition in L02 cells. This study shows that MFA improves lipid deposition in L02 cells by regulating the CaMKK2-AMPK pathway through miR-378b.
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Humanos , Etanol/toxicidad , Proteínas Quinasas Activadas por AMP/metabolismo , Hígado Graso , Triglicéridos , MicroARNs/genética , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/genéticaRESUMEN
Objective:To understand the relationship between lipid accumulation product (LAP) and hyperuricemia in physical examination population.Methods:This was a cross-sectional study. The analysis was based on baseline data from a retrospective cohort study. Total of 44 294 people who received physical examination in the Health Management Center of Xiangya Hospital of Central South University from January to December 2012 were selected as subjects with whole-group sampling method. All the subjects aged ≥18 years with complete study variables. The minimum waist circumference of the subjects was calculated to determine the criteria for calculating LAP in those population. With LAP as the observed variable and hyperuricemia as the outcome variable, LAP was divided into four groups according to the interquartile interval (Q 1-Q 4 groups): group Q 1<10.56 cm·mmol/L, 10.56 cm·mmol/L≤Q 2<20.79 cm·mmol/L, 20.79 cm·mmol/L≤Q 3<38.94 cm·mmol/L, Q 4≥38.94 cm·mmol/L. Five models were constructed with logistic regression analysis. No confounding factors was adjusted in Model 1, model 2 was adjusted for age and gender; and model 3 was further adjusted for body mass index, hypertension, hyperlipidemia, creatinine and glomerular filtration rate; model 4 was further adjusted education level, occupation, health insurance, smoking, drinking, diet scores and physical exercise; model 5 was further adjusted the family history of gout, diabetes and hypertension. And the relationship between different LAP levels and hyperuricemia was analyzed. Results:In this study, the minimum waist circumference in the physical examination population was 58 cm and 53 cm for men and women, respectively. The total incidence of hyperuricemia was 13.4% in this population, 5.94% for women and 19.40% for men. When the confounding factors were not adjusted (model 1), the risk of hyperuricemia in women′s LAP Q 2 to Q 4 groups was 1.76 times (95% CI: 1.42-2.17), 5.08 times (95% CI: 4.20-6.14) and 12.58 times (95% CI: 10.43-15.18), and it was 1.68 times (95% CI: 1.43-1.96), 2.74 times (95% CI: 2.36-3.18), and 5.32 times (95% CI: 4.62-6.14) in men, respectively. After gender stratification and adjustment for confounding factors (model 5), the risk still existed, compared with that in Q 1 group of LAP, the risk of hyperuricemia in women in Q 4 group was 8.28 times higher (95% CI: 2.50-27.38) and 3.31 times higher in men (95% CI: 1.57-6.95). Conclusion:The risk of hyperuricemia in health examination population increases with LAP, especially in women.
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Objective To explore the association of (cardiometabolic index , CMI ) and ( lipid accumulation product , LAP ) with the prevalence of hypertension in adults in Pingshan District, Shenzhen, and to evaluate the predictive value of CMI and LAP for the prevalence of hypertension. Methods A cross-sectional survey was conducted, in which 1000 permanent residents aged 18-69 years in Pingshan District, Shenzhen were randomly selected as survey subjects. The data were collected using questionnaires, physical measurements and blood tests, and the relationship between CMI, LAP and hypertension prevalence was analyzed using logistic regression models. Results A total of 987 subjects were included in the analysis, including 471 (47.72%) males and 516 (52.28%) females, with an average age of 40.9 ± 11.1 years. Subjects of different genders were divided into groups Q1 to Q4 according to quartiles of CMI and LAP, and the prevalence of hypertension increased with increasing levels of CMI and LAP in both men and women (P for trend < 0.001). Logistic regression analysis revealed that after adjusting for variables such as age and occupation, the OR for hypertension was 1.251 (1.025-1.526) and 1.685 (1.001-2.836) for men and women, respectively, for each standard deviation increase in CMI; the OR for hypertension was 3.519 (1.343-9.222) for men in the Q4 group, compared to the CMI subgroup Q1. For each standard deviation increase in LAP, the ORs for hypertension were 1.355 (1.089-1.686) and 1.825 (1.023-3.254) for men and women, respectively; compared to LAP subgroup Q1, the ORs for hypertension in the male Q3 and Q4 groups were 2.554 (1.103-5.909) and 5.322 (2.393-11.834), while the OR for hypertension in the female Q4 group was 2.906 (1.096-7.703). ROC analysis revealed that the area under the curve (AUC) for CMI, LAP, and BMI was 0.671, 0.704, and 0.702 for males, and 0.660, 0.722, and 0.697 for females, respectively. The AUC for LAP was greater than that for CMI for different genders (P < 0.01). Conclusion The greater the CMI and LAP values in adults in Pingshan District, Shenzhen , the higher the prevalence of hypertension. CMI and LAP have certain values in predicting the prevalence of hypertension.
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OBJECTIVE To explore the mechanism of Yishen tongluo formula (YSTLF) in improving abnormal lipid metabolism based on the sterol regulatory element binding proteins (SREBPs) pathway. METHODS Using C57BLKS/J (db/db) mice as model and C57BLKS/J (db/m) mice as normal control, the mechanism of 1, 2.5 and 5 g/kg YSTLF improving abnormal lipid metabolism of db/db mice was investigated by determining the liver coefficient, the contents of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), observing steatosis and lipid accumulation in liver tissue of mice, detecting the protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription levels of Srebp- 1c, Srebp-2 and their downstream lipid metabolism-related target genes (Fasn, Acc1, Scd5, Fads1, Hmgcr, Dhcr24, Insig-1, Fdps) in liver tissue of mice. Using low-fat cultured human liver cancer cell HepG2 as an in vitro cell model for abnormal lipid metabolism, and 25-HC (SREBPs inhibitor, 10 μmol/L) as the control, the effects of 125, 250 and 500 μg/mL YSTLF on protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription of SREBP-1c, SREBP-2 and their downstream lipid metabolism-related target genes were investigated to verify the mechanism in vitro. RESULTS 1, 2.5, 5 g/kg YSTLF significantly reduced the levels of TC, TG and LDL, the percentage of lipid droplet-positive region in liver tissue and liver coefficient, significantly down-regulated protein expressions of Pre-SREBP-1, n-SREBP-1, Pre-SREBP-2 and n-SREBP-2, and mRNA transcription of Srebp-1c, Srebp-2 and their downstream target genes in liver tissue, while significantly increased HDL level, with statistical significance (P<0.05 or P<0.01). In the cell experiment in vitro, the expressions of the above-mentioned proteins and genes in the cells treated with YSTLF at 125, 250 and 500 μg/mL for 24 hours were consistent with those in the animal experiment; there was no significant difference in the expressions of the above-mentioned proteins and genes between inhibitor control group and 250, 500 μg/mL YSTLF groups (P>0.05). CONCLUSIONS YSTLF can regulate the expression of transcription factor SREBPs, so as to inhibit the high expression of fatty acid and cholesterol synthesis-related genes, promote the degradation of TC and TG, improve the abnormality of lipid metabolism and inhibit lipid accumulation, thus playing the role of lipid-lowering.
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This study aims to investigate the impact of hepatocyte nuclear factor 1β (HNF1b) on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum (PAOA-flavone)-promoted small ubiquitin-related modifier (SUMO) modification in the atheroprotective efficacy of HNF1b. HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics, dual-luciferase reporter gene assay, and chromatin immunoprecipitation. HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages, leading to a depression in atherosclerotic plaque formation in low-density lipoprotein (LDL) receptor-deficient (LDLR-/-) mice. Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification. The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages. PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1 (SAE1) expression and SAE1-catalyzed SUMOylation of the HNF1b protein, which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient (ApoE-/-) mice. Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration. In summary, HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis. This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated, SAE1-catalyzed SUMOylation of the HNF1b protein.
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Ratones , Animales , Polygonatum/metabolismo , Sumoilación , Factor Nuclear 1-beta del Hepatocito/metabolismo , Aterosclerosis/metabolismo , Flavonas , LípidosRESUMEN
Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.
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Aim To examine the effect of peptide P3 on lipid accumulation in RAW264.7 cells and the underlying molecular mechanism. Methods MTT method was used to screen the concentration of peptide P3 and oxidized low density lipoprotein(ox-LDL),and RAW.264.7 cells were induced to form foam cells by ox-LDL with 80 mg·L
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Aim To study the effect of Rubus irritans Focke extract on adipogenic differentiation of 3T3-L1 preadipocytes, and to further explore the potential mechanism of Rubus irritans Focke on adipocyte metabolism, so as to provide a new basis for the prevention and treatment of obesity. Methods Rubus irritans Focke extract was separated and prepared by MCI medium pressure chromatographic column. MTT method was used to detect cell proliferation, and oil red 0 staining and kit test was used to to detect the level of lipid accumulation. Western blot was employed to detect the expressions of peroxisome proliferator-activated receptor ¦y (PPAR7), CCAAT enhancer binding protein a (C/ EBPa), adenosine 5'-monophosphate activated protein kinase (AMPK) and phosphorylated AMPK (p-AMPK) protein. Results When the concentration of Rubus irritans Focke extract was less than 100 mg •L
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Aim To investigate the effect of echinatin on the non-alcoholic fatty liver disease model of free fatty acids ( FFA) -induced HepG2 cells and its mechanism. Methods The experimental groups were divided into control group, FFA model group and echinatin group (0.3 , 1, 3 μmol • L
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Arrhythmogenic cardiomyopathy (ACM), a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes, accounts for 20% of sudden cardiac death and lacks effective treatment. It is often caused by mutations in desmosome proteins, with Desmoglein-2 (DSG2) mutations as a common etiology. However, the mechanism underlying the accumulation of fibrofatty in ACM remains unknown, which impedes the development of curative treatment. Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2 (CS-Dsg2 -/-). Heart failure and cardiac lipid accumulation were observed in CS-Dsg2 -/- mice. We demonstrated that these phenotypes were caused by decline of fatty acid (FA) β-oxidation resulted from impaired mammalian target of rapamycin (mTOR) signaling. Rapamycin worsened while overexpression of mTOR and 4EBP1 rescued the FA β-oxidation pathway in CS-Dsg2 -/- mice. Reactivation of PPARα by fenofibrate or AAV9-Pparα significantly alleviated the lipid accumulation and restored cardiac function. Our results suggest that impaired mTOR-4EBP1-PPARα-dependent FA β-oxidation contributes to myocardial lipid accumulation in ACM and PPARα may be a potential target for curative treatment of ACM.
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Objective To explore the regulative effect of α-Hederin on the proliferation and invasion of NSCLC and investigate its related molecular mechanism. Methods After A549 and HCC-1833 cells were treated with a concentration gradient of α-Hederin for 24 and 48 h, the OD450nm was detected by using CCK8 assays, and the IC50 was calculated.The A549 and HCC-1833 cells were divided into the blank control and α-Hederin groups in accordance with IC50 values.Cell proliferation was detected by EdU assays, and cell cycle transformation and cell apoptosis were detected by flow cytometry.Cell mobility was detected by using Transwell and scratch assays.SREBP1 and FASN protein expression levels were detected through Western blot analysis, and cell lipid accumulation was detected via oil red O staining. Results The survival rate of lung cancer cells decreased significantly with the increase of α-Hederin concentration, and the IC50 values of A549 and HCC-1833 cells at 48 h were 15 and 25 μg/ml, respectively.Compared with the blank control group, cells proliferation and migration were significantly inhibited, cells were blocked in the G1/S phase, the apoptosis rate increased, and the protein expression and lipid accumulation of SREBP1/FASN significantly reduced after α-Hederin treatment. Conclusion α-Hederin can inhibit the proliferation and migration, G1/S phase transition and induce the apoptosis of NSCLC cells and hinder the malignant progression of NSCLC by downregulating the expression of SREBP1 and FASN and reducing the accumulation of cell lipids.
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ObjectiveTo explore the mechanism of Gegen Qinliantang (GQT) in improving ectopic lipid accumulation in the liver of db/db mice with type 2 diabetes mellitus (T2DM) by regulating the adenosine monophosphate-activated protein kinase (AMPK)-forkhead box O3a (FoxO3a) autophagy axis, to provide a scientific basis for clarifying the hypoglycemic mechanism of GQT and its clinical application. MethodSeventy-five spontaneous T2DM db/db mice and 15 normal db/m mice were selected and maintained on a regular diet for one week, followed by the measurement of blood glucose. They were then randomly divided into six groups, with 15 mice in each group, including normal group (0.2 g·kg-1 saline), metformin group (0.2 g·kg-1), high-, medium, and low-dose GQT group (31.9, 19.1, 6.9 g·kg-1), and model group (0.2 g·kg-1 saline). The mice were orally administered the corresponding drugs once daily for 12 weeks. Fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were detected. Fasting insulin (FINS) and free fatty acid (FFA) levels were measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in liver tissues were observed by hematoxylin-eosin (HE) staining. The protein expression levels of phosphorylated (p)-AMPK, p-FoxO3a, and autophagy-related proteins microtubule-associated protein 1 light chain 3 Ⅱ (LC3Ⅱ) and p62 were detected using Western blot. Immunofluorescence was used to detect the expression of hypoxia-inducible factor-1α (HIF-1α) in liver tissues. Real-time polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression of AMPK, FoxO3a, and LC3 in liver tissues. ResultCompared with the normal group, the model group showed pathological changes in liver tissues, increased FBG, HbA1c, FINS, and FFA levels (P<0.01), increased protein expression levels of p-AMPK, p62, and HIF-1α, decreased protein expression levels of p-FoxO3a and LC3Ⅱ in liver tissues (P<0.01), decreased mRNA expression of AMPK, and increased expression of FoxO3a (P<0.01). Compared with the model group, the treatment groups showed relieved liver tissue lesions and decreased FBG, HbA1c, FINS, and FFA levels (P<0.01). The expression of p-AMPK, p62, and HIF-1α increased, while the expression of p-FoxO3a showed a dose-dependent decrease in the high-dose GQT group. The expression of LC3Ⅱ increased in the metformin group and the high-dose GQT group (P<0.01). The mRNA expression of AMPK showed a dose-dependent increase, and the expression of FoxO3a showed a dose-dependent decrease in the treatment groups (P<0.01). ConclusionGQT can improve ectopic lipid accumulation in the liver of T2DM db/db mice, which may be related to the regulation of the AMPK-FoxO3a autophagy axis.
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The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that obesity strongly contributes to the development of cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on the public and on health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia and formation of visceral fat in other non-adipose tissues to evoke cardiovascular disease, liver diseases. Adipose tissue can also secrete adipokines and inflammatory cytokines to affect the local microenvironment, induce insulin resistance, hyperglycemia, and activate associated inflammatory signaling pathways. This further exacerbates the development and progression of obesity-associated diseases. Although some progress in the treatment of obesity has been achieved in preclinical and clinical studies, the progression and pathogenesis of obesity-induced diseases are complex and unclear. We still need to understand their links to better guide the treatment of obesity and associated diseases. In this review, we review the links between obesity and other diseases, with a view to improve the future management and treatment of obesity and its co-morbidities.
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Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome.
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Objective:To explore the relationship between lipid accumulation product (LAP) and disease activity, nutritional status in patients with Crohn disease (CD).Methods:The clinical data of 74 patients with CD in the Affiliated Hospital of Yangzhou University from July 2020 to June 2021 were retrospectively analyzed. The patients were divided into active group (32 cases) and remission group (42 cases) according to simplified Crohn disease activity index (CDAI). The general clinical data, laboratory examination results and body fat indexes were recorded, body fat indexes including body mass index (BMI), waist circumference, waist-to-height ratio, LAP and nutritional risk screening 2002 (NRS2002) score. Spearman method was used for correlation analysis; the receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of LAP in predicting the disease activity and nutritional status in patients with CD.Results:The proportion of males, body weight, hemoglobin, albumin, total cholesterol, triglyceride and high-density lipoprotein cholesterol in active group were significantly lower than those in remission group: 46.9% (15/32) vs. 71.4% (30/42), (53.58 ± 8.13) kg vs. (61.05 ± 9.38) kg, (109.94 ± 23.70) g/L vs. (134.19 ± 18.03) g/L, (34.01 ± 5.71) g/L vs. (39.15 ± 4.27) g/L, (3.23 ± 0.68) mmol/L vs. (3.66 ± 0.74) mmol/L, (1.12 ± 0.36) mmol/L vs. (1.34 ± 0.55) mmol/L and (0.91 ± 0.23) mmol/L vs. (1.04 ± 0.33) mmol/L, the nutritional risk rate, platelet count, C-reactive protein and erythrocyte sedimentation rate were significantly higher than those in remission group: 68.8% (22/32) vs. 19.0% (8/42), (317.97 ± 130.19) ×10 9/L vs. (194.00 ± 51.91) × 10 9/L, 14.15 (6.15, 41.35) mg/L vs. 1.51 (0.22, 5.58) mg/L and 40.00 (20.50, 64.25) mm/1 h vs. 9.00 (3.00, 20.00) mm/1 h, and there were statistical differences ( P<0.01 or <0.05); there were no statistical difference in age, height, total protein and low-density lipoprotein cholesterol between the two groups ( P>0.05). The BMI, waist circumference, waist-to-height ratio and LAP in active group were significantly lower than those in remission group: 19.46 (17.70, 21.45) kg/m 2 vs. 21.08 (18.87, 23.12) kg/m 2, (72.51 ± 5.92) cm vs. (77.67 ± 7.27) cm, 0.44 ± 0.03 vs. 0.46 ± 0.04, 13.42 (5.07, 17.72) cm·mmol/L vs. 15.49 (9.37, 31.71) cm·mmol/L, the NRS2002 was significantly higher than that in remission group: 3.00 (1.00, 3.75) scores vs. 1.00 (0, 2.00) scores, and there were statistical differences ( P<0.01 or <0.05). Spearman correlation analysis result showed that LAP was positively correlated with BMI, waist circumference and waist-to-height ratio ( r = 0.701, 0.766 and 0.829; P<0.01); LAP was negatively correlated with NRS2002 score, platelet count and erythrocyte sedimentation rate ( r =- 0.609, - 0.249 and - 0.243; P<0.01 or<0.05). ROC curve analysis result showed that the areas under the curve of LAP predicting disease remission and nutritional status improvement in patients with CD were 0.645 and 0.832 (95% CI 0.520 to 0.770 and 0.739 to 0.925), the best cut-off values were 20.89 and 12.86 cm·mmol/L, the sensitivities were 45.2% and 81.8%, and the specificities were 87.5% and 73.3%. Conclusions:LAP has good predictive value for disease remission and nutritional status improvement in patients with CD.
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Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.