Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.198
Filtrar
1.
Wei Sheng Yan Jiu ; 50(1): 93-99, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33517968

RESUMEN

OBJECTIVE: To evaluate the possibility of high-fat diet to induce metabolic syndrome and to alter intestinal development, liver function and intestinal microbiotaof C57 BL/6 J mice. METHODS: Total 40 of male C57 BL/6 J aged 3 weeks old were randomly divided into two groups: control group and high-fat diet group. After one week of adaptive feeding, the tested mice in high-fat diet group were fed with high-fat diet for 20 weeks, while those in control group were fed with ordinary diet. During the intervention, the body weight of the tested mice was measured weekly and fasting blood glucose(FBG) was measured monthly. Before the end of the experiment, the oral glucose tolerance test(OGTT) of the tested mice was conducted and the fecal 16 S rRNA sequencing was used to profile fecal microbiota of the test mice. Real-time qPCR was used to analyze the concentration of fecal bifidobacteria. Viscera coefficient of liver, spleen and pancreas, visceral fat-body ratio and intestinal length were measured. The indexes of liver function and the levels of serum lipids, leptin and adiponectin were also measured. Liver inflammation and fat infiltration were observed by anatomical pathological analysis. RESULTS: After intervention of high fat diet, the body weight, FBG, oral glucose tolerance, the fat-body ratio, the levels of serum lipids, leptin and adiponectin of mice were significantly increased(P<0. 05). The inflammatory state of liver and the degree of fat infiltration increased. The length of intestine decreased(P<0. 05). The concentration of Bifidobacterium decreased(P<0. 05), however, the concentration of B. bifidum and B. angulatum increased(P<0. 05). The ACE, Chao1, Shannon and Simpson indexes of the high-fat diet were significantly lower than that of the control group(P<0. 05). Firmicutes, Proteobacteria and Deferribacteres were found significantly more in high-fat diet group(P<0. 05), while Bacteroidetes and Verrucomicrobia were apparently more in control group(P<0. 05). CONCLUSION: High-fat diet could induce the metabolic syndrome in tested C57 BL/6 J, and lead to the damage of intestinal development, abnormality of liver tissue and its function, decrease diversity of intestinal microbiota, and the transformation of intestinal microbiota community to obesity type.


Asunto(s)
Microbioma Gastrointestinal , Síndrome Metabólico , Animales , Dieta Alta en Grasa/efectos adversos , Hígado , Masculino , Síndrome Metabólico/etiología , Ratones , Ratones Endogámicos C57BL , Obesidad
2.
Gene ; 775: 145441, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33482280

RESUMEN

Exercise training with anti-inflammatory effects can improve insulin sensitivity in muscle tissue. This study investigated the effects of eight-week swimming exercises on lipid profile, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and peroxisome proliferator-activated receptor gamma (PPAR-γ) in gastrocnemius muscle of rats fed with high-fat diet (HFD). Thirty-two healthy male Wistar rats (8 weeks, 200 ± 20 g) were randomly divided into four groups (n = 8 each group): the control (C), aerobic exercise (E), HFD, and HFD + aerobic exercise (HFD & E). The exercise training protocol consisted of swimming 60 min/day, 5 days/week for eight weeks. Serum levels of glucose, insulin, and lipid profile were measured at end of the study. Protein expressions of TLR4, TNF-α, and IL-6 were determined by immunohistochemical method. Gene expression of TLR4/MyD88, TNF-α, IL-6, and PPAR-γ was evaluated by a real-time polymerase chain reaction in gastrocnemius muscle. HFD fed rats showed higher levels of cholesterol and LDL-c that were similar in weight gain. Meanwhile, the HFD group had a higher gene expression of TLR4, MyD88, TNF-α, IL-6, and lower gene expression of PPAR-γ compared to the control group (p < 0.05). Muscle protein expression of TLR4, TNF-α, IL-6 was lower in the E and HFD&E groups (especially when compared to HFD group, P < 0.05). We also showed a decrease in TLR4/MyD88 mRNA and an increase in PPAR-γ mRNA in gastrocnemius of E and HFD&E groups (compared to HFD group, p < 0.05). Insulin resistance in HFD&E groups show a significant decrease compared to the HFD group (p < 0.05). It seems that swimming aerobic exercise for eight weeks controlled the destructive effects of HFD on muscle inflammatory pathways along with the down-regulation of the TLR4/MyD88, inflammatory cytokine, and up-regulation PPAR-γ mRNA. It appears that the down-regulation in the expression of TLR4/MyD88 mRNA reduces the muscle pro-inflammatory cytokines, such as IL-6 and TNF-α, whose action may be caused by the adaptation of swimming aerobic exercise (an increase of PPAR-γ). Therefore, local and systemic inflammatory changes due to HFD and obesity may be affected by metabolic adaptations of aerobic exercise training, which requires further studies.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Resistencia a la Insulina/inmunología , Músculo Esquelético/metabolismo , Condicionamiento Físico Animal/métodos , Natación/fisiología , Animales , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Músculo Esquelético/efectos de los fármacos , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
3.
Nat Commun ; 12(1): 650, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33510172

RESUMEN

Hepatic inflammation is the driving force for the development and progression of NASH. Treatment targeting inflammation is believed to be beneficial. In this study, adoptive transfer of CD4+ T cells converted double negative T cells (cDNT) protects mice from diet-induced liver fat accumulation, lobular inflammation and focal necrosis. cDNT selectively suppress liver-infiltrating Th17 cells and proinflammatory M1 macrophages. IL-10 secreted by M2 macrophages decreases the survival and function of cDNT to protect M2 macrophages from cDNT-mediated lysis. NKG2A, a cell inhibitory molecule, contributes to IL-10 induced apoptosis and dampened suppressive function of cDNT. In conclusion, ex vivo-generated cDNT exert potent protection in diet induced obesity, type 2 diabetes and NASH. The improvement of outcome is due to the inhibition on liver inflammatory cells. This study supports the concept and the feasibility of potentially utilizing this autologous immune cell-based therapy for the treatment of NASH.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Inflamación/metabolismo , Hígado/metabolismo , Macrófagos/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Traslado Adoptivo/métodos , Animales , Linfocitos T CD4-Positivos/inmunología , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Dieta Alta en Grasa/efectos adversos , Progresión de la Enfermedad , Perfilación de la Expresión Génica/métodos , Inflamación/genética , Interleucina-10/metabolismo , Hígado/patología , Macrófagos/clasificación , Macrófagos/inmunología , Masculino , Ratones Endogámicos C57BL , Subfamília C de Receptores Similares a Lectina de Células NK/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/terapia , Obesidad/etiología , Obesidad/metabolismo , Obesidad/terapia
4.
Phytomedicine ; 80: 153388, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33113501

RESUMEN

BACKGROUND: Insulin resistance (IR) and lipotoxicity were evidenced as the major nonalcoholic steatohepatitis (NASH) initiators. However, absence of the effective treatment against NASH progression raised our aim to discover a new promising insulin modulator and NSH preventer. PURPOSE: Our study aimed to extract and prepare a nitriles rich fraction (NRF) from Diceratella elliptica (DC.) Jonsell, investigate its insulin-sensitizing & anti-NASH potentialities and address its molecular targets in IR-NASH pathogenesis. STUDY DESIGN: NRF was prepared using natural autolysis method and compounds were identified. Then, seventy male Wistar rats were feed high fat diet (HFD) or normal pellets for 35 days. In day 14th, HFD rats were injected by Streptozotocin (STZ) once and treatment was started in day 21st with either NRF (30, 60 and 120 mg/kg; orally) or pioglitazone (PioG) (10 mg/kg; i.p) beside HFD. While, NRF-alone rats were treated with NRF (120 mg/kg; orally) beside the normal pellets. Body weight, glucose homeostasis, hepatopathological examinations were performed. METHODS: Gas liquid chromatography-mass spectrophotometry (GLC/MS) was used for compounds' identification while spectrophotometer was used for total glucosinolates (GLS) quantification. Also, the biochemical and molecular investigations concerned with liver lipotoxicity, oxidative stress, inflammation and insulin signaling pathway were investigated and confirmed with the computational prediction of the major compounds' targets. RESULTS: Butenyl and benzyl GLS were the major along with other volatile compounds. NRF had significantly increased the insulin sensitivity and improved NASH-hisptopathology showing hepatoprotective effect. While, the fraction's anti-NASH potentiality was evidenced in the normalized hepatic steatosis markers, inflammation and oxidative stress key transcriptional factors resulting in induction of insulin receptor substrates (IRSs) phosphorylation and its downstream effectors. CONCLUSION: NRF has reversed IR, stimulated leptin secretion and prevented NASH initiation showing promising anti-NASH and anti-fibrotic effects.


Asunto(s)
Brassicaceae/química , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Extractos Vegetales/farmacología , Animales , Dieta Alta en Grasa/efectos adversos , Glucosinolatos/análisis , Leptina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Nitrilos/química , Nitrilos/farmacología , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Pioglitazona/farmacología , Extractos Vegetales/química , Ratas Wistar , Transducción de Señal
5.
Environ Pollut ; 270: 116243, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33326921

RESUMEN

BACKGROUND: Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue. OBJECTIVES: We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice. METHODS: Pregnant C57BL6/J mice were exposed to BPS (1.5 µg/kg bw/day ie a human equivalent dose of 0.12 µg/kg bw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed. RESULTS: In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females. CONCLUSIONS: BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females.


Asunto(s)
Dieta Alta en Grasa , Efectos Tardíos de la Exposición Prenatal , Animales , Dieta Alta en Grasa/efectos adversos , Femenino , Ratones , Fenoles/toxicidad , Embarazo , Sulfonas
6.
Food Chem ; 340: 128169, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33007695

RESUMEN

Polyphenols from cambuci (CBC) (Campomanesia phaea (O. Berg.)), a Brazilian native fruit, were investigated on therapeutic actions mitigating insulin resistance and hepatic steatosis in high-fat-sucrose diet (HFS) induced obese mice. For this, C57BL/6J mice fed with a obesogenic and diabetogenic HFS diet were administered with either water or two CBC doses (36 or 74 mg gallic acid equivalent (GAE)/kg body weight) by gavage from week 6 to week 14 (end-point) of HFS feeding. CBC reduced body weight gain, inflammation, hepatic steatosis, hyperglycemia, glucose intolerance, and insulin resistance in liver and skeletal muscle of obese mice, and such effects were associated with activation of Akt and AMPK in these tissues. In conclusion, polyphenols from CBC show important therapeutic actions ameliorating obesity-associated complications.


Asunto(s)
Resistencia a la Insulina , Myrtaceae/química , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/complicaciones , Polifenoles/farmacología , Animales , Dieta Alta en Grasa/efectos adversos , Frutas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/inducido químicamente , Obesidad/metabolismo , Polifenoles/uso terapéutico
7.
PLoS One ; 15(12): e0241779, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33315867

RESUMEN

Accurate quantification and characterization of atherosclerotic plaques with MRI requires high spatial resolution acquisitions with excellent image quality. The intrinsically better signal-to-noise ratio (SNR) at high-field clinical 7T compared to the widely employed lower field strengths of 1.5 and 3T may yield significant improvements to vascular MRI. However, 7T atherosclerosis imaging also presents specific challenges, related to local transmit coils and B1 field inhomogeneities, which may overshadow these theoretical gains. We present the development and evaluation of 3D, black-blood, ultra-high resolution vascular MRI on clinical high-field 7T in comparison lower-field 3T. These protocols were applied for in vivo imaging of atherosclerotic rabbits, which are often used for development, testing, and validation of translatable cardiovascular MR protocols. Eight atherosclerotic New Zealand White rabbits were imaged on clinical 7T and 3T MRI scanners using 3D, isotropic, high (0.63 mm3) and ultra-high (0.43 mm3) spatial resolution, black-blood MR sequences with extensive spatial coverage. Following imaging, rabbits were sacrificed for validation using fluorescence imaging and histology. Image quality parameters such as SNR and contrast-to-noise ratio (CNR), as well as morphological and functional plaque measurements (plaque area and permeability) were evaluated at both field strengths. Using the same or comparable imaging parameters, SNR and CNR were in general higher at 7T compared to 3T, with a median (interquartiles) SNR gain of +40.3 (35.3-80.1)%, and a median CNR gain of +68.1 (38.5-95.2)%. Morphological and functional parameters, such as vessel wall area and permeability, were reliably acquired at 7T and correlated significantly with corresponding, widely validated 3T vessel wall MRI measurements. In conclusion, we successfully developed 3D, black-blood, ultra-high spatial resolution vessel wall MRI protocols on a 7T clinical scanner. 7T imaging was in general superior to 3T with respect to image quality, and comparable in terms of plaque area and permeability measurements.


Asunto(s)
Aterosclerosis/diagnóstico , Imagenología Tridimensional/métodos , Angiografía por Resonancia Magnética/métodos , Placa Aterosclerótica/diagnóstico por imagen , Animales , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/lesiones , Aorta Abdominal/patología , Aterosclerosis/etiología , Aterosclerosis/patología , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Estudios de Factibilidad , Humanos , Angiografía por Resonancia Magnética/instrumentación , Masculino , Placa Aterosclerótica/etiología , Placa Aterosclerótica/patología , Conejos , Reproducibilidad de los Resultados , Relación Señal-Ruido
8.
PLoS One ; 15(12): e0243911, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33326461

RESUMEN

Peroxisome proliferator-activated receptor α/δ (PPAR α/δ), regulating glucolipid metabolism and immune inflammation, has been identified as an effective therapeutic target in non-alcoholic steatohepatitis (NASH). Dual PPAR α/δ agonist, such as GFT505 (also known as elafibranor), demonstrated potential therapeutic effect for NASH in clinical trials. To profile the regulatory network of PPAR α/δ agonist in NASH, the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) induced NASH model was used to test the pharmacodynamics and transcriptome regulation of GFT505 in this study. The results showed that GFT505 ameliorated hepatic steatosis, inflammation and fibrosis in CDAHFD mice model. RNA-sequencing yielded 3995 up-regulated and 3576 down-regulated genes with GFT505 treatment. And the most significant differentialy expressed genes involved in glucolipid metabolism (Pparα, Acox1, Cpt1b, Fabp4, Ehhadh, Fabp3), inflammation (Ccl6, Ccl9, Cxcl14) and fibrosis (Timp1, Lamc3, Timp2, Col3a1, Col1a2, Col1a1, Hapln4, Timp3, Pik3r5, Pdgfα, Pdgfß, Tgfß1, Tgfß2) were confirmed by RT-qPCR. The down-regulated genes were enriched in cytokine-cytokine receptor interaction pathway and ECM-receptor interaction pathway, while the up-regulated genes were enriched in PPAR signaling pathway and fatty acid degradation pathway. This study provides clues and basis for further understanding on the mechanism of PPAR α/δ agonist on NASH.


Asunto(s)
Deficiencia de Colina/genética , Enfermedad del Hígado Graso no Alcohólico/genética , PPAR alfa/genética , Receptores Citoplasmáticos y Nucleares/genética , Aminoácidos/metabolismo , Animales , Chalconas/farmacología , Colina/genética , Deficiencia de Colina/patología , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/genética , Humanos , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , PPAR alfa/agonistas , Propionatos/farmacología , Receptores Citoplasmáticos y Nucleares/agonistas , Transducción de Señal/genética
9.
Zhongguo Zhong Yao Za Zhi ; 45(21): 5265-5272, 2020 Nov.
Artículo en Chino | MEDLINE | ID: mdl-33350244

RESUMEN

The aim of this paper was to investigate the mechanism of the active peptide DP17 of Eupolyphaga steleophaga in the treatment of hyperlipidemia rats. HPLC and MADIL-TOF/TOF-MS were used for the amino acid sequence analysis and solid-phase synthesis on the active peptide of E. steleophaga which were obtained by biomimetic enzymatic hydrolysis, separation and purification. The hyperlipidemia model was established by feeding with high-fat diet.Twenty days later, the rats in the blank group and the model group were given the saline and the rats in remaining groups were given the corresponding drugs by oral administration. After administration for 4 weeks, the levels of triglyceride(TG), total cholesterol(TC) and low density lipoprotein(LDL) in serum, the levels of TG, TC, adenosine monophosphate(AMP), adenosine triphosphate(ATP) in liver tissues and TG in feces were detected, respectively. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of liver tissues. The Real-time fluorescence quantitative PCR method was used to detect the expression of acetyl coa carboxylase(ACC) and hydroxymethylglutaryl-coa reductase(HMGCR) mRNA in liver tissues. The expression of mammalian target of rapamycin(mTORC1) protein and adenosine 5'-monophosphate-activated protein kinase(AMPK) in liver tissues were detected by Western blot. The analysis showed that the amino acid sequence of active peptide from E. steleophaga was DAVPGAGPAGCHPGAGP(DP17). The results of pharmacological experiments showed that after oral administration of DP17 in rats, the levels of TG, TC and LDL in serum as well as TG and TC levels in liver tissues were significantly decreased(P<0.05), while the levels of AMP, ATP in liver tissues and TG content in feces were significantly increased(P<0.05); the liver steatosis of rats was significantly relieved; the expression of ACC, HMGCR mRNA and mTORC1 protein in liver tissues were significantly reduced, while the expression of AMPK phosphorylated protein was significantly increased(P<0.05). DP17, the active peptide of E. steleophag can significantly reduce lipid accumulation in liver tissues, and it may play a role in reducing blood lipids by regulating the energy metabolism balance in the body and activating AMPK/mTOR signaling pathway.


Asunto(s)
Hiperlipidemias , Animales , Dieta Alta en Grasa/efectos adversos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/genética , Lípidos , Hígado , Péptidos , Ratas , Triglicéridos
10.
PLoS One ; 15(12): e0244013, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33320899

RESUMEN

The generation of large metabolomic data sets has created a high demand for software that can fit statistical models to one-metabolite-at-a-time on hundreds of metabolites. We provide the %polynova_2way macro in SAS to identify metabolites differentially expressed in study designs with a two-way factorial treatment and hierarchical design structure. For each metabolite, the macro calculates the least squares means using a linear mixed model with fixed and random effects, runs a 2-way ANOVA, corrects the P-values for the number of metabolites using the false discovery rate or Bonferroni procedure, and calculate the P-value for the least squares mean differences for each metabolite. Finally, the %polynova_2way macro outputs a table in excel format that combines all the results to facilitate the identification of significant metabolites for each factor. The macro code is freely available in the Supporting Information.


Asunto(s)
Hígado/metabolismo , Metaboloma , Metabolómica/métodos , Programas Informáticos , Animales , Dieta Alta en Grasa/efectos adversos , Hígado Graso/etiología , Hígado Graso/prevención & control , Hígado/microbiología , Espectrometría de Masas/métodos , Probióticos/uso terapéutico , Porcinos
11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(8): 892-900, 2020 Aug 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-33053529

RESUMEN

OBJECTIVES: To investigate the effects of environmental enrichment on cognitive behavior and the expression of adenosine triphosphate binding cassette transporter A7 (ABCA7) in hippocampus of the adolescent mice with high fat diet. METHODS: A total of healthy 3-week-old male C57BL/6J mice were randomly divided into 3 groups: a control (Con) group, a high fat diet (HFD) group, and a high fat diet+environmental enrichment (HFD+EE) group, with 10 mice in each group. The Con group was given normal diet. The HFD group was given high fat diet. The HFD+EE group was given high fat diet; at the same time, they treated by environmental enrichment. After 10 weeks, open field test was used to detect activity. Novel object recognition test and Y maze test were used to detect cognitive behavior. After the test, the brain was collected and used to detect the protein expression of ABCA7 in the hippocampus by immunohistochemistry and Western blotting. And quantitative RT-PCR (RT-qPCR) was used to detect the ABCA7 mRNA expression level in the hippocampus. RESULTS: There was no significant difference in the total movement distance in the mice among the 3 groups (P>0.05). In the novel object recognition test, the discrimination index of the HFD group was much lower than that of the Con group, and the difference was significant (P<0.01). The discrimination index of the HFD+EE group was higher than that of the HFD group, and the difference was significant (P<0.01). In the Y maze test, there was no significant difference in the percentage of time spent on the new arm among the mice in the 3 groups (P=0.1279). The percentage of entries in new arm in the HFD group was much lower than that in the Con group, and the difference was significant (P<0.01). The percentage of the entries in new arm in the HFD+EE group was significantly higher than that in the HFD group (P<0.05). The results of immunohistochemistry showed that ABCA7 was positively expressed in the cytoplasm of hippocampal neurons in the mice from these 3 groups, and the expression of ABCA7 in the hippocampus of the HFD group was lower than that of the Con group (CA1: P<0.01, CA3: P=0.06), while the expression of ABCA7 in hippocampus of HFD+EE group was higher than that of HFD group (CA1: P=0.23, CA3: P<0.05). Western blotting results showed that compared with the Con group, the protein level of ABCA7 in the hippocampus of the HFD group was significantly reduced (P<0.05), while compared with the Con group, the protein level of ABCA7 in the hippocampus of the HFD+EE group showed an upward trend (P=0.06). The results of RT-qPCR showed that the mRNA level of ABCA7 in the hippocampus of HFD group was significantly lower than that of the Con group (P<0.01), while the mRNA level of ABCA7 in the hippocampus of HFD+EE group was significantly higher than that of the HFD group (P<0.01). CONCLUSIONS: High fat diet in adolescent can impair cognitive function with a decrease in the expression of ABCA7 in hippocampus, which can be ameliorate by environmental enrichment.


Asunto(s)
Transportadoras de Casetes de Unión a ATP , Adenosina Trifosfato , Dieta Alta en Grasa , Hipocampo , Animales , Cognición , Dieta Alta en Grasa/efectos adversos , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL
12.
Wei Sheng Yan Jiu ; 49(5): 785-822, 2020 Sep.
Artículo en Chino | MEDLINE | ID: mdl-33070825

RESUMEN

OBJECTIVE: Establish the prokaryotic expression system of Amuc_1100 protein from Akkermansia muciniphila, and analyze the effects of this protein on the body weight, blood glucose, intestinal barrier function and Akkermansia muciniphila abundance in rats fed with high-fat diet combined streptozotocin(STZ)injection. METHODS: PCR product of Amuc_1100 Gene(Gene ID: 34174504) was linked to the double enzyme-digested pET-26 b plasmid vector. The recombinant expression plasmid pET-26 b-Amuc_1100 then transformed into E. Coli BL21. The verified clones through sequence analysis were induced by the addition of IPTG. High-fat diet rats were interfered with the purified protein at high and low doses. The changes of body weight, blood glucose, intestinal barrier function and Akkermansia muciniphila abundance were analyzed. RESULTS: The recombinant expression plasmid pET-26 b-Amuc_1100 was successfully constructed. The sequencing result showed 100% similarity to the Amuc_1100 gene in GenBank. The molecular weight of the protein obtained was 42 kDa. The intervention of Amuc_1100 protein can reduce the weight of rats fed with high-fat diet combined STZ injection to some extent, improve barrier function and increase the abundance of Akkermansia muciniphila in intestine. CONCLUSION: The prokaryotic expression system of Amuc_1100 protein was successfully constructed, which has a certain regulatory effect on rats fed with high-fat diet combined STZ injection.


Asunto(s)
Dieta Alta en Grasa , Escherichia coli , Animales , Dieta Alta en Grasa/efectos adversos , Escherichia coli/genética , Ratas , Estreptozocina/toxicidad , Verrucomicrobia
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(10): 1406-1414, 2020 Oct 30.
Artículo en Chino | MEDLINE | ID: mdl-33118513

RESUMEN

OBJECTIVE: To study the effects of high-fat (HF) diet and exercise on the expressions of asprosin and CTRP6 in adipose tissues in different regions of rats during mid-gestation. METHODS: Pregnant SD rats were fed on a standard chow diet or a high-fat (60% fat content) diet for 14 days starting on gestation day (GD) 1. Starting from GD3, the rats fed either on normal or high-fat diet in the exercise groups (CH-RW and HF-RW groups) were allowed access to the running wheels for voluntary running, and those in sedentary groups (CH-SD and HF-SD groups) remained sedentary. At the end of the 14 days, adipose tissues were sampled from different regions of the rats for detecting the mRNA and protein expressions of asprosin and CTRP6 using RT-qPCR and Western blotting. RESULTS: The mRNA expression of asprosin in retroperitoneal adipose tissues was significantly higher in HF-RW group than in the other 3 groups (P < 0.0001). Asprosin mRNA expression in subcutaneous adipose tissues was significantly higher in HF-SD group than in CH-SD group (P=0.0234) and comparable between HF-RW and CH-SD groups (P=0.0494). CTRP6 mRNA expression in retroperitoneal adipose tissues was also significantly higher in HF-RW group than in the other groups (P < 0.0001), and CTRP6 protein expression was signficiantly higher in HF-RW group than in CH-RW and HF-SD groups (P < 0.05). In subcutaneous adipose tissues, CTRP6 mRNA expression was significantly higher in CH-RW group than in HF-SD and HF-RW groups (P < 0.05). The protein expression level of CTRP6 in subcutaneous adipose tissues showed a significant negative correlation with blood glucose (r=-0.6038, P=0.0172), while its expression in retroperitoneal adipose tissues was positively correlated with blood glucose (r=0.5305, P= 0.0285); the mRNA expression levels of asprosin and CTRP6 were significantly lower in subcutaneous than in retroperitoneal adipose tissues (P < 0.0001). CONCLUSIONS: High-fat diet and exercise during mid-gedtation can affect the expression levels of asprosin and CTRP6 in adipose tissues of rats in a site-specific manner.


Asunto(s)
Dieta Alta en Grasa , Grasa Intraabdominal , Adipoquinas , Animales , Glucemia , Dieta Alta en Grasa/efectos adversos , Femenino , Embarazo , Ratas , Ratas Sprague-Dawley
14.
J Oleo Sci ; 69(10): 1287-1295, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33028753

RESUMEN

Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects including lipid-lowering that have been extensively studied. However, its bioavailability is low. To investigate the effect of nanoemulsified rice bran wax policosanol (NPOL) on plasma homocysteine, heart and liver histology in hyperlipidemic rats, high-fat diet containing 2.5% cholesterol was used to induce hyperlipidemia in Sprague Dawley rats. The hyperlipidemic rats were treated with NPOL and rice bran wax policosanol (POL) in comparison with normal diet (ND), high-cholesterol diet (HCD) and simvastatin-treated rats. Plasma homocysteine, heart and liver histology, and hepatic mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) were evaluated. The NPOL group, similar to the simvastatin group, showed reduced plasma homocysteine, preserved heart and liver histology, and down-regulated hepatic PPARG mRNA in comparison to the control group, and was better than the POL group. The results suggest that the modest effect of NPOL on homocysteine and preservation of heart and liver histology could be through the regulation of PPARG expression on a background of increased assimilation of rice bran wax policosanol.


Asunto(s)
Cardiotónicos , Alcoholes Grasos/farmacología , Alcoholes Grasos/uso terapéutico , Hiperlipidemias/metabolismo , Hiperlipidemias/patología , Hígado/metabolismo , Hígado/patología , Miocardio/metabolismo , Miocardio/patología , Oryza/química , PPAR gamma/genética , PPAR gamma/metabolismo , Fitoterapia , Ceras/química , Animales , Dieta Alta en Grasa/efectos adversos , Expresión Génica/efectos de los fármacos , Homocisteína/sangre , Hiperlipidemias/etiología , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley
15.
Nat Commun ; 11(1): 4981, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-33020469

RESUMEN

Antagonism or agonism of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) prevents weight gain and leads to dramatic weight loss in combination with glucagon-like peptide-1 receptor agonists in preclinical models. Based on the genetic evidence supporting GIPR antagonism, we previously developed a mouse anti-murine GIPR antibody (muGIPR-Ab) that protected diet-induced obese (DIO) mice against body weight gain and improved multiple metabolic parameters. This work reconciles the similar preclinical body weight effects of GIPR antagonists and agonists in vivo, and here we show that chronic GIPR agonism desensitizes GIPR activity in primary adipocytes, both differentiated in vitro and adipose tissue in vivo, and functions like a GIPR antagonist. Additionally, GIPR activity in adipocytes is partially responsible for muGIPR-Ab to prevent weight gain in DIO mice, demonstrating a role of adipocyte GIPR in the regulation of adiposity in vivo.


Asunto(s)
Adipocitos/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Receptores de la Hormona Gastrointestinal/agonistas , Receptores de la Hormona Gastrointestinal/antagonistas & inhibidores , Adipocitos/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Fármacos Antiobesidad/química , Fármacos Antiobesidad/uso terapéutico , Anticuerpos/farmacología , Anticuerpos/uso terapéutico , Peso Corporal/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , AMP Cíclico/metabolismo , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/metabolismo , Polipéptido Inhibidor Gástrico/farmacología , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/patología , Receptores de la Hormona Gastrointestinal/deficiencia , Receptores de la Hormona Gastrointestinal/metabolismo
16.
PLoS One ; 15(10): e0239671, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33002059

RESUMEN

In spite of the widespread use of electronic cigarettes, also known as e-cigarettes, and the proposed adverse cardiac effects of nicotine, the detrimental effects of e-cigarettes on the heart are not well known. This study examines the detrimental effects of e-cigarettes with nicotine at doses that yield circulating nicotine and cotinine in the ranges similar to the levels found in habitual smokers, and a high fat diet (HFD) on cardiac structure and function in a commonly used model of diet-induced obesity (DIO). C57BL/6J mice on an HFD were exposed to e-cigarette in the presence (2.4% nicotine) or absence (0% nicotine) of nicotine and saline aerosol for 12 weeks. Echocardiographic data demonstrated a decrease in left ventricular (LV) fractional shortening, LV ejection fraction, and velocity of circumferential fiber shortening (VCF) in mice treated with e-cigarette (2.4% nicotine) compared to e-cigarette (0% nicotine) or saline exposed mice. Cardiomyocytes (CMs) of mice treated with e-cigarette (2.4% nicotine) exhibited LV abnormalities, including lipid accumulation (ventricular steatosis), myofibrillar derangement and destruction, and mitochondrial hypertrophy, as revealed by transmission electron microscopy. The detrimental effects of e-cigarettes (2.4% nicotine) on cardiac structure and function was accompanied by increased oxidative stress, plasma free fatty acid levels, CM apoptosis, and inactivation of AMP-activated protein kinase and activation of its downstream target, acetyl-CoA-carboxylase. Our results indicate profound adverse effects of e-cigarettes (2.4% nicotine) on the heart in obese mice and raise questions about the safety of the nicotine e-cigarettes use.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Sistemas Electrónicos de Liberación de Nicotina , Corazón/efectos de los fármacos , Ratones Obesos , Miocardio/patología , Fumar/efectos adversos , Animales , Cotinina/sangre , Ecocardiografía , Ácidos Grasos no Esterificados/sangre , Corazón/fisiopatología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión , Miocardio/ultraestructura , Nicotina/efectos adversos , Nicotina/sangre , Estrés Oxidativo/efectos de los fármacos , Disfunción Ventricular Izquierda/inducido químicamente
17.
Nat Commun ; 11(1): 4458, 2020 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-32895383

RESUMEN

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling.


Asunto(s)
Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factor 1 de Crecimiento de Fibroblastos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Hipotálamo/efectos de los fármacos , Proteínas Recombinantes/administración & dosificación , Proteína Relacionada con Agouti/metabolismo , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Glucemia/análisis , Comunicación Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/patología , Dieta Alta en Grasa/efectos adversos , Sacarosa en la Dieta/administración & dosificación , Sacarosa en la Dieta/efectos adversos , Humanos , Hipotálamo/citología , Hipotálamo/patología , Inyecciones Intraventriculares , Leptina/genética , Masculino , Melanocortinas/metabolismo , Hormonas Estimuladoras de los Melanocitos/administración & dosificación , Ratones , Ratones Noqueados , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , RNA-Seq , Receptor de Melanocortina Tipo 4/genética , Receptores de Melanocortina/antagonistas & inhibidores , Receptores de Melanocortina/metabolismo , Inducción de Remisión/métodos , Transducción de Señal/efectos de los fármacos , Análisis de la Célula Individual , Técnicas Estereotáxicas , Transcriptoma/efectos de los fármacos
18.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 261-264, 2020 May.
Artículo en Chino | MEDLINE | ID: mdl-32981283

RESUMEN

Objective: To investigate the effects of liraglutide combined with vitamin D on high-fat-induced non-alcoholic fatty liver disease (NAFLD) mice and its potential mechanism. Methods: C57BL/6 mice were divided into control group, NAFLD model group, liraglutide group, vitamin D group and liraglutide combined with vitamin D group. Each group consisted of 10 mice. The control group was fed with normal diet for 12 weeks; the model group was fed with high-fat diet for 12 weeks; the liraglutide group, vitamin D group and combined group were fed with high-fat diet for 12 weeks, From the 9th week, the three groups of mice were intraperitoneally injected with liraglutide (0.6 mg/kg), vitamin D(250 mg/(kg·d) ) by gavage, and combination. After 12 weeks of feeding, the blood and liver tissues of mice in each group were collected for biochemical and pathological examination, and the phosphorylation level of AMP-activated protein kinase (AMPK) in liver tissues of mice in each group was detected by immunoblotting. Results: Liraglutide or vitamin D alone or in combination could improve liver lipid accumulation (triglycerides: 6.0±0.7 vs 3.8±0.3, 3.9±0.3 and 2.1±0.2, all P<0.05; cholesterol: 1.4±0.5 vs 0.9±0.2, 0.8±0.2 and 0.5±0.1, all P<0.05) and steatosis (NAFLD activity score: 2.4±0.3 vs 1.0±0.2, 0.9±0.1 and 0.6±0.1, all P<0.05) in NAFLD mice. In addition, compared with liraglutide or vitamin D group, liraglutide combined with vitamin D treatment was more effective, and might be related to the regulation of insulin resistance and AMPK phosphorylation. Conclusion: The results showed that vitamin D could enhance the therapeutic effect of liraglutide on NAFLD induced by high fat, and may be related to the regulation of insulin resistance and AMPK phosphorylation.


Asunto(s)
Liraglutida , Enfermedad del Hígado Graso no Alcohólico , Vitamina D , Animales , Dieta Alta en Grasa/efectos adversos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Liraglutida/farmacología , Liraglutida/uso terapéutico , Hígado/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Vitamina D/farmacología , Vitamina D/uso terapéutico
19.
Nat Commun ; 11(1): 4737, 2020 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-32968070

RESUMEN

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P < 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Reposicionamiento de Medicamentos , Inflamasomas/efectos de los fármacos , Resistencia a la Insulina , Inhibidores de la Transcriptasa Inversa/farmacología , Adipocitos/metabolismo , Animales , Supervivencia Celular , ARN Helicasas DEAD-box/metabolismo , Diabetes Mellitus Tipo 2/prevención & control , Dieta Alta en Grasa/efectos adversos , VIH-1/efectos de los fármacos , Hepatitis B , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Células Musculares/metabolismo , Ribonucleasa III/metabolismo
20.
Nat Commun ; 11(1): 4765, 2020 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-32958780

RESUMEN

Fatty acids (FAs) are essential nutrients, but how they are transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn delivers FAs into adipocytes. During the process, binding of FAs to CD36 activates its downstream kinase LYN, which phosphorylates DHHC5, the palmitoyl acyltransferase of CD36, at Tyr91 and inactivates it. CD36 then gets depalmitoylated by APT1 and recruits another tyrosine kinase SYK to phosphorylate JNK and VAVs to initiate endocytic uptake of FAs. Blocking CD36 internalization by inhibiting APT1, LYN or SYK abolishes CD36-dependent FA uptake. Restricting CD36 at either palmitoylated or depalmitoylated state eliminates its FA uptake activity, indicating an essential role of dynamic palmitoylation of CD36. Furthermore, blocking endocytosis by targeting LYN or SYK inhibits CD36-dependent lipid droplet growth in adipocytes and high-fat-diet induced weight gain in mice. Our study has uncovered a dynamic palmitoylation-regulated endocytic pathway to take up FAs.


Asunto(s)
Antígenos CD36/metabolismo , Endocitosis/fisiología , Ácidos Grasos/metabolismo , Lipoilación , Células 3T3-L1 , Aciltransferasas/metabolismo , Adipocitos/metabolismo , Animales , Antígenos CD36/deficiencia , Antígenos CD36/genética , Caveolas/metabolismo , Células Cultivadas , Dieta Alta en Grasa/efectos adversos , Humanos , Gotas Lipídicas/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación , Obesidad/tratamiento farmacológico , Fosforilación , Transducción de Señal , Quinasa Syk/antagonistas & inhibidores , Quinasa Syk/metabolismo , Aumento de Peso/efectos de los fármacos , Familia-src Quinasas/antagonistas & inhibidores , Familia-src Quinasas/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA