Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.053
Filtrar
1.
Zhonghua Yi Xue Za Zhi ; 100(6): 456-459, 2020 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-32146770

RESUMO

Objective: To compare the curative effect of mesenchymal stem cells derived from human Wharton's Jelly(WJ-MSC) or adipose(AD-MSC) culture supernatant on endothelial cells angiogenesis. Methods: WJ-MSC and AD-MSC were isolated, identified, and the culture supernatant of stem cells was collected.The WJ-MSC or AD-MSC supernatant co-cultured with the endothelial cells. The expression levels of pro-angiogenic and anti-angiogenic genes of endothelial cells were assessed using qRT-PCR analysis, and the effects of stem cell culture supernatant on angiogenesis were evaluated by performing a tube formation assay in vitro. Results: After adding WJ-MSC and AD-MSC culture supernatant, the expression levels of pro-angiogenic genes in endothelial cells were upregulated, and the expression levels of anti-angiogenic genes were downregulated significantly in both experimental groups compared to the control group (P<0.01), and tube formation of endothelial cells was also significantly increased in both experimental groups as determined by the increase of the tube length ((43.2±9.2) mm vs (94.3±13.2)mm, (86.1±7.2)mm, P<0.01). Conclusion: The results showed that AD-MSC culture supernatant can promote endothelial cells angiogenesis and its curative effect is similar to that of WJ-MSC.


Assuntos
Células-Tronco Mesenquimais , Geleia de Wharton , Adipócitos , Técnicas de Cultura de Células , Diferenciação Celular , Proliferação de Células , Técnicas de Cocultura , Células Endoteliais , Humanos
2.
Life Sci ; 248: 117474, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112869

RESUMO

BACKGROUND/OBJECTIVES: Nicotinamide N-methyltransferase (NNMT) is a novel regulator of energy homeostasis in adipocytes. NNMT expression in adipose tissue is increased in obesity and diabetes. Knockdown of NNMT prevents mice from developing diet-induced obesity, which is closely linked to insulin resistance. An early sign of systemic insulin resistance is reduced expression of glucose transporter 4 (GLUT4) selectively in adipose tissue. Adipose tissue-specific knockout and overexpression of GLUT4 cause reciprocal changes in NNMT expression. The aim of the current study was to elucidate the mechanism that regulates NNMT expression in adipocytes. METHODS: 3T3-L1 adipocytes were cultured in media with varying glucose concentrations or activators and inhibitors of intracellular pathways. NNMT mRNA and protein levels were measured with quantitative polymerase chain reaction and Western blotting. RESULTS: Glucose deprivation of 3T3-L1 adipocytes induced a 2-fold increase in NNMT mRNA and protein expression. This effect was mimicked by inhibition of glucose transport with phloretin, and by inhibition of glycolysis with the phosphoglucose isomerase inhibitor 2-deoxyglucose. Conversely, inhibition of the pentose phosphate pathway did not affect NNMT expression. Pharmacological activation of the cellular energy sensor AMP-activated protein kinase (AMPK) and inhibition of the mammalian target of rapamycin (mTOR) pathway caused an increase in NNMT levels that was similar to the effect of glucose deprivation. Activation of mTOR with MHY1485 prevented the effect of glucose deprivation on NNMT expression. Furthermore, upregulation of NNMT levels depended on functional autophagy and protein translation. CONCLUSION: Glucose availability regulates NNMT expression via an mTOR-dependent mechanism.


Assuntos
Adipócitos/efeitos dos fármacos , Transportador de Glucose Tipo 4/genética , Glucose/farmacologia , Nicotinamida N-Metiltransferase/genética , Serina-Treonina Quinases TOR/genética , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Transporte Biológico/efeitos dos fármacos , Diferenciação Celular , Desoxiglucose/farmacologia , Metabolismo Energético/genética , Regulação da Expressão Gênica , Glucose/metabolismo , Transportador de Glucose Tipo 4/antagonistas & inibidores , Transportador de Glucose Tipo 4/metabolismo , Glucose-6-Fosfato Isomerase/antagonistas & inibidores , Glucose-6-Fosfato Isomerase/genética , Glucose-6-Fosfato Isomerase/metabolismo , Homeostase/genética , Camundongos , Morfolinas/farmacologia , Nicotinamida N-Metiltransferase/antagonistas & inibidores , Nicotinamida N-Metiltransferase/metabolismo , Via de Pentose Fosfato/efeitos dos fármacos , Via de Pentose Fosfato/genética , Floretina/farmacologia , Biossíntese de Proteínas , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Triazinas/farmacologia
3.
Chem Biol Interact ; 318: 108978, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32044341

RESUMO

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) accumulates in human body, probably influencing adipocyte differentiation and causing various toxic effects, including wasting syndrome. Recently, orientin, a phenolic compound abundant in natural health products, has been shown to have antioxidant properties. We investigated the protective effects of orientin against TCDD-induced adipocyte dysfunction and its underlying mechanisms. In this study, orientin suppressed TCDD-induced loss of lipid accumulation. Orientin inhibited TCDD-driven decreases in the levels of peroxisome proliferator-activated receptor γ and adiponectin. Orientin also reduced TCDD-induced prostaglandin E2, and cytosolic phospholipase A2α levels, and increased TCDD-inhibited peroxisome proliferator-activated receptor gamma coactivator 1-alpha levels in 3T3-L1 adipocytes. TCDD reduced the levels of insulin receptor substrate 1 and glucose transporter 4, and decreased insulin-stimulated glucose uptake activity; however, orientin diminished these TCDD-induced effects. These results suggest that orientin may have beneficial effects on the prevention of TCDD-induced wasting syndrome and type II diabetes mellitus accompanied by insulin resistance.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Flavonoides/farmacologia , Glucosídeos/farmacologia , Insulina/metabolismo , Dibenzodioxinas Policloradas/toxicidade , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , Animais , Dinoprostona , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Camundongos
4.
Gene ; 735: 144404, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32018013

RESUMO

Glucose uptake in adipocytes is crucial for regulating systemic metabolism. Long noncoding RNAs (lncRNAs), defined as being transcripts with lengths exceeding 200 nucleotides that are not translated, are recently identified regulators of cellular functions. Previously, we have shown that an lncRNA, "down-regulated expression by hepatitis B virus X" (dreh), is involved in glucose transport in skeletal muscle cells. Here, we aimed to examine the involvement of dreh in glucose transport in 3T3-L1 adipocytes. Expression analysis showed that dreh was expressed in 3T3-L1 fibroblasts and adipocytes. Knockdown of dreh expression using its specific siRNAs lowered the glucose concentration of the medium and facilitated [3H]-2-deoxyglucose transport in adipocytes. Additionally, dreh silencing enhanced the protein expression of glucose transporter (GLUT4) in the plasma membrane of adipocytes. Treatment with siRNA against vimentin attenuated the glucose-lowering effect of dreh depletion. These results suggest that the repression of dreh facilitates glucose transport via increased GLUT4 expression in the plasma membrane through the involvement of vimentin in 3T3-L1 adipocytes. In conclusion, dreh is the first observed lncRNA that regulates glucose transport in adipocytes and could serve as a novel therapeutic target for diabetes by modulating adipocyte function. Considering the new function of dreh, we propose that dreh be renamed "down-regulated expression-related hexose/glucose transport enhancer."


Assuntos
Adipócitos/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Glucose/metabolismo , RNA Longo não Codificante/genética , Vimentina/metabolismo , Animais , Linhagem Celular , Fibroblastos/metabolismo , Camundongos , RNA Longo não Codificante/metabolismo
5.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(2): 220-225, 2020 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-32030955

RESUMO

Objective: To investigate the effect of circulating estrogen level on the outcome of free fat grafting in nude mice. Methods: Eighteen female nude mice aged 6-8 weeks (weighing, 20-25 g) were randomly divided into 3 groups ( n=6). The nude mice in the ovariectomized group were treated with ovariectomy. The nude mice in the high estrogen group and the normal estrogen group only made the same incision to enter the peritoneum without ovariectomy. The nude mice in the high estrogen group were given the estradiol (0.2 mg/g) every 3 days for 30 days. The other two groups were given the same amount of PBS every 3 days. At 30 days after operation, the tail vein blood of nude mice in 3 groups were detected by estradiol ELISA kit, and the free fat (0.3 mL) donated by the females was injected into the sub-scalp of nude mice. After 8 weeks of fat grafting, the samples were taken for gross observation and weighing, and the prepared slices were stained with HE staining, CD31-perilipin fluorescence staining, immunohistochemical staining of uncoupling protein 1 (UCP1), and immunofluorescence staining of estrogen receptor α. The diameter of adipocytes and vascular density of adipose tissue were measured. The mRNA expressions of UCP1 and estrogen receptor α were detected by realtime fluorescence quantitative PCR (qRT-PCR). Results: All nude mice survived during experiment. ELISA test showed that the concentration of estradiol significantly decreased in the ovariectomized group and increased in the high estrogen group compared with the normal estrogen group ( P<0.05). At 8 weeks after fat grafting, the graft volume from large to small was ovariectomized group, normal estrogen group, and high estrogen group. There was significant difference in wet weight between the ovariectomized group and high estrogen group ( P<0.05). Section staining showed that compared with the normal estrogen group, the adipocytes in the ovariectomized group were larger, the expression of peri-lipoprotein was weaker, the vascular density decreased, and the expressions of UCP1 was negative, and the estrogen receptor α positive cells reduced. The above observation results in the high estrogen group were contrary to those in the ovariectomized group. There were significant differences in the diameter of adipocytes, the vascular density of adipose tissue, the number of the estrogen receptor α positive cells between groups ( P<0.05). The results of qRT-PCR showed that the mRNA expressions of UCP1 and estrogen receptor α significantly increased in the high estrogen group and decreased in the ovariectomized group compared with the normal estrogen group, and the differences were significant ( P<0.05). Conclusion: The level of circulating estrogen has a significant effect on the outcome of free fat grafting in nude mice. Low estrogen level leads to hypertrophy of graft adipocytes, while high estrogen level leads to the production of a large amount of beige fat and high vascular density in fat grafts, which may be related to the activation of estrogen receptor α on adipocytes.


Assuntos
Tecido Adiposo , Adipócitos , Animais , Estradiol , Estrogênios , Feminino , Camundongos , Camundongos Nus
6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(2): 226-233, 2020 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-32030956

RESUMO

Objective: To explore the possibility of constructing tissue engineered adipose by adipose tissue derived extracellular vesicles (hAT-EV) combined with decellularized adipose tissue (DAT) scaffolds, and to provide a new therapy for soft tissue defects. Methods: The adipose tissue voluntarily donated by the liposuction patient was divided into two parts, one of them was decellularized and observed by HE and Masson staining and scanning electron microscope (SEM). Immunohistochemical staining and Western blot detection for collagen type Ⅰ and Ⅳ and laminin were also employed. Another one was incubated with exosome-removed complete medium for 48 hours, then centrifuged to collect the medium and to obtain hAT-EV via ultracentrifugation. The morphology of hAT-EV was observed by transmission electron microscopy; the nanoparticle tracking analyzer (NanoSight) was used to analyze the size distribution; Western blot was used to analyse membrane surface protein of hAT-EV. Adipose derived stem cells (ADSCs) were co-cultured with PKH26 fluorescently labeled hAT-EV, confocal fluorescence microscopy was used to observe the uptake of hAT-EV by ADSCs. Oil red O staining was used to evaluate adipogenic differentiation after hAT-EV and ADSCs co-cultured for 15 days. The DAT was scissored and then injected into the bilateral backs of 8 C57 mice (6-week-old). In experimental group, 0.2 mL hAT-EV was injected weekly, and 0.2 mL PBS was injected weekly in control group. After 12 weeks, the mice were sacrificed, and the new fat organisms on both sides were weighed. The amount of new fat was evaluated by HE and peri-lipoprotein immunofluorescence staining to evaluate the ability of hAT-EV to induce adipogenesis in vivo. Results: After acellularization of adipose tissue, HE and Masson staining showed that DAT was mainly composed of loosely arranged collagen with no nucleus; SEM showed that no cells and cell fragments were found in DAT, and thick fibrous collagen bundles could be seen; immunohistochemical staining and Western blot detection showed that collagen type Ⅰ and Ⅳ and laminin were retained in DAT. It was found that hAT-EV exhibited a spherical shape of double-layer envelope, with high expressions of CD63, apoptosis-inducible factor 6 interacting protein antibody, tumor susceptibility gene 101, and the particle size of 97.9% hAT-EV ranged from 32.67 nmto 220.20 nm with a peak at 91.28 nm. Confocal fluorescence microscopy and oil red O staining showed that hAT-EV was absorbed by ADSCs and induced adipogenic differentiation. In vivo experiments showed that the wet weight of fat new organisms in the experimental group was significantly higher than that in the control group ( t=2.278, P=0.048). HE staining showed that the structure of lipid droplets in the experimental group was more than that in the control group, and the collagen content in the control group was higher than that in the experimental group. The proportion of new fat in the experimental group was significantly higher than that in the control group ( t=4.648, P=0.017). Conclusion: DAT carrying hAT-EV can be used as a new method to induce adipose tissue regeneration and has a potential application prospect in the repair of soft tissue defects.


Assuntos
Tecido Adiposo , Adipócitos , Animais , Diferenciação Celular , Células Cultivadas , Espaço Extracelular , Humanos , Camundongos , Células-Tronco , Engenharia Tecidual , Tecidos Suporte
7.
Life Sci ; 246: 117404, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32035128

RESUMO

AIMS: The study aims to investigate the effect of plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of fibrinolytic process, on blood glucose in type 2 diabetes mellitus (T2DM) and its mechanism. MATERIALS AND METHODS: We developed a highly potent and highly specific PAI-1 inhibitor, named PAItrap3, based on the inactivated urokinase. Meanwhile, a single point mutation of PAItrap3 (i.e., PAItrapNC) was parallelly prepared as negative control. PAItrap3 was intravenously injected into type 2 diabetic (T2D) mice and its effect on metabolic system was evaluated by measuring the levels of blood glucose, PAI-1, and tumor necrosis factor alpha (TNF-α) in T2D mice. KEY FINDINGS: PAItrap3 significantly reduced the high blood glucose level and PAI-1 level in streptozotocin-induced T2D mice. PAItrapNC did not have any hypoglycemic effect at all on T2D mice. Mechanistically, both PAI-1 and TNF-α levels were attenuated by the administration of PAItrap3. In addition, we observed that PAItrap3 reduced the amount of fat droplets in adipocytes. SIGNIFICANCE: These findings provide clear evidence for PAI-1 to participate in inflammation and obesity mediated hyperglycemia, and open up a new prospect for the treatment of T2DM by PAI-1 inhibition.


Assuntos
Glicemia/análise , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Inibidor 1 de Ativador de Plasminogênio/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Adipócitos/efeitos dos fármacos , Animais , Masculino , Inibidor 1 de Ativador de Plasminogênio/sangue
8.
Adv Exp Med Biol ; 1234: 1-13, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32040851

RESUMO

Adipose tissue contribution to body mass ranges from 6% in male athletes to over 25% in obese men and over 30% in obese women. Crosstalk between adipocytes and cancer cells that exist in close proximity can lead to changes in the function and phenotype of both cell types. These interactions actively alter the tumour microenvironment (TME). Obesity is one of the major risk factors for multiple types of cancer, including breast cancer. In obesity, the increase in both size and number of adipocytes leads to instability of the TME, as well as increased hypoxia within the TME, which further enhances tumour invasion and metastasis. In this chapter, we will discuss the diverse aspects of adipocytes and adipocyte-derived factors that affect the TME as well as tumour progression and metastasis. In addition, we discuss how obesity affects the TME. We focus primarily on breast cancer but discuss what is known in other cancer types when relevant. We finish by discussing the studies needed to further understand these complex interactions.


Assuntos
Adipócitos , Neoplasias/patologia , Obesidade/patologia , Microambiente Tumoral , Tecido Adiposo , Neoplasias da Mama/patologia , Feminino , Humanos
9.
Plant Foods Hum Nutr ; 75(1): 103-109, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31902039

RESUMO

Adipose tissue is an endocrine organ and its endocrine function is closely associated with type 2 diabetes mellitus. Valeriana officinalis (Valerian) exerts some physiological effects; however, its influence on adipocytes remains unclear. We investigated the effect of methanolic Valerian root extract (Vale) on 3T3-L1 adipocytes. Vale (1, 10, and 100 µg/mL) dose-dependently promoted adipocyte differentiation with increasing lipid accumulation. In addition, Vale significantly increased the mRNA levels in genes associated with adipocyte differentiation, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α , and adipocyte protein 2, in dose-dependent manner. Vale also significantly enhanced mRNA and protein levels in adiponectin. A PPARγ antagonist assay and a PPARγ binding assay revealed that Vale-induced increased adipocyte differentiation and adiponectin production were partly associated with direct binding to PPARγ. Valerenic acid, a characteristic component in Valerian, also demonstrated the ability to induce adipocyte differentiation and adiponectin secretion, suggesting that it is one of the functional components in Vale.


Assuntos
Diabetes Mellitus Tipo 2 , Valeriana , Células 3T3-L1 , Adipócitos , Adipogenia , Adiponectina , Animais , Diferenciação Celular , Metanol , Camundongos , PPAR gama , Extratos Vegetais
10.
Cell Prolif ; 53(2): e12756, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31943490

RESUMO

OBJECTIVES: To evaluate the rapid repair potential of adipose-derived stem cells (ADSCs) co-overexpressing VEGF and GDNF on bilateral cavernous nerve injury (BCNI) in rat models. Progressive fibrosis of the penis that occurs shortly after BCNI is a key cause of clinical treatment difficulty of erectile dysfunction (ED). Traditional medications are ineffective for ED caused by BCNI. ADSCs have shown therapeutic effects in animal models, but disappointing in clinical treatment suggests that we should explore optimal treatment of it. MATERIALS AND METHODS: We extracted ADSCs from rat epididymis. Lentiviral transfection was verified by western blot and immunofluorescence. Thirty-six SD rats (10 weeks old) were randomly divided into six groups (n = 6 per group): sham surgery, and remaining five BCNI groups transplanted PBS or ADSCs which were genetically modified by vehicle, VEGF (ADSC-V), GDNF (ADSC-G), or VEGF&GDNF (ADSC-G&V) around major pelvic ganglion (MPG). We investigated the therapeutic effects of BCNI rat model which is characterized by ED, penile tissue fibrosis and hypoxia, and lack of nitrogen nerves or vascular atrophy. RESULTS: Erectile function was almost recovered after 2 weeks of transplantation of ADSC-G&V, promoted cavernous nerve repair, prevented penile fibrosis and preserving the vascular endothelium, which was significant differences amongst ADSC-V or ADSC-G. Moreover, GM-ADSCs were detected in MPG and penis, indicating that their participation in repair of target organs and transverse nerves. CONCLUSIONS: These promising data indicate that ADSCs co-overexpressed VEGF and GDNF-induced synergistic effects, make it a potential tool for recovering of erectile function speedily after BCNI.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Disfunção Erétil/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Neurogênese/fisiologia , Células-Tronco/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Humanos , Masculino , Ereção Peniana/fisiologia , Pênis/metabolismo , Ratos , Ratos Sprague-Dawley , Transplante de Células-Tronco
14.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(1): 124-131, 2020 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-31939247

RESUMO

Objective: To investigate the effects of adipose-derived stem cell released exosomes (ADSC-Exos) on wound healing in diabetic mice. Methods: The ADSCs were isolated from the adipose tissue donated by the patients and cultured by enzymatic digestion. The supernatant of the 3rd generation ADSCs was used to extract Exos (ADSC-Exos). The morphology of ADSC-Exos was observed by transmission electron microscopy. The membrane-labeled proteins (Alix and CD63) were detected by Western blot, and the particle size distribution was detected by nanoparticle tracking analyzer. The fibroblasts were isolated from the skin tissue donated by the patients and cultured by enzymatic digestion. The 5th generation fibroblasts were cultured with PKH26-labeled ADSC-Exos, and observed by confocal fluorescence microscopy. The effects of ADSC-Exos on proliferation and migration of fibroblasts were observed with cell counting kit 8 (CCK-8) and scratch method. Twenty-four 8-week-old Balb/c male mice were used to prepare a diabetic model. A full-thickness skin defect of 8 mm in diameter was prepared on the back. And 0.2 mL of ADSC-Exos and PBS were injected into the dermis of the experimental group ( n=12) and the control group ( n=12), respectively. On the 1st, 4th, 7th, 11th, 16th, and 21st days, the wound healing was observed and the wound healing rate was calculated. On the 7th, 14th, and 21st days, the histology (HE and Masson) and CD31 immunohistochemical staining were performed to observe the wound structure, collagen fibers, and neovascularization. Results: ADSC-Exos were the membranous vesicles with clear edges and uniform size; the particle size was 40-200 nm with an average of 102.1 nm; the membrane-labeled proteins (Alix and CD63) were positive. The composite culture observation showed that ADSC-Exos could enter the fibroblasts and promote the proliferation and migration of fibroblasts. Animal experiments showed that the wound healing of the experimental group was significantly faster than that of the control group, and the wound healing rate was significantly different at each time point ( P<0.05). Compared with the control group, the wound healing of the experimental group was better. There were more microvessels in the early healing stage, and more deposited collagen fibers in the late healing stage. There were significant differences in the length of wound on the 7th, 14th, and 21st days, the number of microvessels on the 7th and 14th days, and the rate of deposited collagen fibers on the 14th and 21st days between the two groups ( P<0.05). Conclusion: ADSC-Exos can promote the wound healing in diabetic mice by promoting angiogenesis and proliferation and migration of fibroblasts and collagen synthesis.


Assuntos
Diabetes Mellitus Experimental , Exossomos , Adipócitos , Animais , Humanos , Masculino , Camundongos , Células-Tronco , Cicatrização
15.
J Agric Food Chem ; 68(7): 2256-2262, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31927923

RESUMO

Fat deposition is one of the most important economic traits of pigs. Decreasing the subcutaneous fat and increasing the intramuscular fat are believed to be an effective way to improve pork quality, which is one of the main goals of pig breeding. Identifying key genes that control porcine lipid metabolism is essential for achieving this goal. Apolipoprotein R (apoR) was identified as the crucial molecule in the process of pig adipose reduction by clenbuterol. In this study, transgenic mice with adipose-tissue-specific overexpression of pig apoR (apoR mice) were constructed. The apoR mice gained less weight than wild-type (WT) mice after 18 weeks of feeding a high-fat diet. A comparison of organs between the two genotypes revealed that the weight of white adipose tissue, including inguinal and epididymal fat tissue, was significantly decreased and the weight of liver tissue was increased in apoR mice compared with WT mice. Glucose and insulin intolerance tests showed that the glucose metabolism of apoR mice was similar to that of WT mice. Histological staining proved that the adipocytes of apoR mice had a reduced average size, and gene expression analysis indicated that lipolysis in the adipose tissue of apoR mice was enhanced. Finally, the primary culture of inguinal adipocytes revealed that apoR promotes lipolysis via the Erk1/2 pathway. Taken together, the results indicate that adipose-tissue-specific expression of pig apoR protects mice from diet-induced obesity by enhancing lipolysis.


Assuntos
Tecido Adiposo/metabolismo , Apolipoproteínas/genética , Obesidade/genética , Obesidade/prevenção & controle , Adipócitos/metabolismo , Animais , Apolipoproteínas/metabolismo , Dieta Hiperlipídica/efeitos adversos , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glucose/metabolismo , Lipólise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Obesidade/metabolismo , Obesidade/fisiopatologia , Suínos
16.
Nat Commun ; 11(1): 578, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996685

RESUMO

Lipid droplets (LDs) are key subcellular organelles for regulating lipid metabolism. Although several subcellular organelles participate in lipid metabolism, it remains elusive whether physical contacts between subcellular organelles and LDs might be involved in lipolysis upon nutritional deprivation. Here, we demonstrate that peroxisomes and peroxisomal protein PEX5 mediate fasting-induced lipolysis by stimulating adipose triglyceride lipase (ATGL) translocation onto LDs. During fasting, physical contacts between peroxisomes and LDs are increased by KIFC3-dependent movement of peroxisomes toward LDs, which facilitates spatial translocations of ATGL onto LDs. In addition, PEX5 could escort ATGL to contact points between peroxisomes and LDs in the presence of fasting cues. Moreover, in adipocyte-specific PEX5-knockout mice, the recruitment of ATGL onto LDs was defective and fasting-induced lipolysis is attenuated. Collectively, these data suggest that physical contacts between peroxisomes and LDs are required for spatiotemporal translocation of ATGL, which is escorted by PEX5 upon fasting, to maintain energy homeostasis.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Jejum/efeitos adversos , Gotículas Lipídicas/metabolismo , Lipólise/fisiologia , Receptor 1 de Sinal de Orientação para Peroxissomos/metabolismo , Peroxissomos/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Análise Espaço-Temporal , Células 3T3-L1/metabolismo , Adipócitos/metabolismo , Animais , Caenorhabditis elegans , Sinais (Psicologia) , Citoesqueleto , Cinesina/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nutrientes , Receptor 1 de Sinal de Orientação para Peroxissomos/genética , Peroxissomos/genética , Transdução de Sinais
17.
Cancer Immunol Immunother ; 69(1): 115-126, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31802182

RESUMO

Pro-inflammatory cytokines are crucial mediators of cancer development, representing potential targets for cancer therapy. The molecular mechanism of a vital pro-inflammatory cytokine, IL-17A, in cancer progression and its potential use in therapy through influencing fatty acid (FA) metabolism, especially FA uptake of cancer cells, remains unknown. In the present study, we used IL-17A and ovarian cancer (OvCa), a representative of both obesity-related and inflammation-related cancers, to explore the interactions among IL-17A, cancer cells and adipocytes (which can provide FAs). We found that in the presence of palmitic acid (PA), IL-17A could directly increase the cellular uptake of PA, leading to the proliferation of OvCa cells via the IL-17A/IL-17RA/p-STAT3/FABP4 axis rather than via CD36. Moreover, in vivo experiments using an orthotopic implantation model in IL-17A-deficient mice demonstrated that endogenous IL-17A could fuel OvCa growth and metastasis with increased expression of FABP4 and p-STAT3. Furthermore, analysis of clinical specimens supported the above findings. Our data not only provide useful insights into the clinical intervention of the growth and metastasis of the tumors (such as OvCa) that are prone to growth and metastasis in an adipocyte-rich microenvironment (ARM) but also provides new insights into the roles of IL-17A in tumor progression and immunomodulatory therapy of OvCa.


Assuntos
Adipócitos/imunologia , Interleucina-17/metabolismo , Neoplasias Ovarianas/imunologia , Ácido Palmítico/metabolismo , Adipócitos/metabolismo , Animais , Antígenos CD36/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Humanos , Interleucina-17/genética , Interleucina-17/imunologia , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Ovário/patologia , Fosforilação , Receptores de Interleucina-17/metabolismo , Proteínas Recombinantes/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Microambiente Tumoral/imunologia
18.
Virchows Arch ; 476(1): 29-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31501988

RESUMO

Adipocytic tumors are frequently encountered in routine practice, and while the vast majority represent commonly encountered tumor types (e.g., benign lipoma), the heterogeneity and rarity of other adipocytic neoplasms can pose diagnostic challenges. Atypical and malignant adipocytic tumors account for approximately 20% of all sarcomas. The 2013 World Health Organization (WHO) classification of soft tissue and bone tumors recognizes four major liposarcoma subtypes, characterized by distinct clinical behavior, distinctive morphologies, as well as unique genetic findings: atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, and pleomorphic liposarcoma. Since the publication of the 2013 WHO classification of soft tissue and bone tumors, the most notable change in the category of adipocytic tumors has been made in the clinicopathologic and molecular characterization of the heterogeneous but distinct group of "atypical low-grade adipocytic neoplasms with spindle cell features," for which the term atypical spindle cell/pleomorphic lipomatous tumor has been proposed. Another substantive change in the group of adipocytic tumors is the introduction of pleomorphic myxoid liposarcoma (myxoid pleomorphic liposarcoma) as an apparently novel subtype of aggressive liposarcoma, especially occurring in children and young adults with a predilection for the mediastinum. This review will further focus upon the diagnostic criteria of these novel emerging entities in the group of adipocytic tumors.


Assuntos
Adipócitos/patologia , Lipoma/patologia , Lipossarcoma/patologia , Humanos , Lipoma/genética , Lipossarcoma/genética , Prognóstico
19.
J Clin Endocrinol Metab ; 105(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31606738

RESUMO

CONTEXT: Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood. OBJECTIVE: The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice. DESIGN: 28 patients with severe obesity were included and stratified into two groups: (1) glucose levels <100 mg/dL and (2) glucose levels >100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects. RESULTS: OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice. CONCLUSIONS: OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance.


Assuntos
Glucose/metabolismo , Homeostase , Obesidade/metabolismo , Oncostatina M/fisiologia , Adipócitos/citologia , Adulto , Animais , Feminino , Transportador de Glucose Tipo 4/genética , Humanos , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Receptores de Oncostatina M/fisiologia
20.
Cell Mol Life Sci ; 77(1): 115-128, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31352534

RESUMO

Adipose tissue is located in discrete depots that are differentially associated with elevated risk of metabolic complications, with fat accretion in visceral depots being most detrimental to metabolic health. Currently, the regulation of specific adipose depot expansion, by adipocyte hypertrophy and hyperplasia and consequently fat distribution, is not well understood. However, a growing body of evidence from in vitro investigations indicates that mature adipocytes secrete factors that modulate the proliferation and differentiation of progenitor, adipose-derived stem cells (ADSCs). It is therefore plausible that endocrine communication between adipocytes and ADSCs located in different depots influences fat distribution, and may therefore contribute to the adverse health outcomes associated with visceral adiposity. This review will explore the available evidence of paracrine and endocrine crosstalk between mature adipocytes and ADSCs that affects adipogenesis, as a better understanding of the regulatory roles of the extracellular signalling mechanisms within- and between adipose depots may profoundly change the way we view adipose tissue growth in obesity and related comorbidities.


Assuntos
Adipócitos/citologia , Adipogenia , Células-Tronco/citologia , Adipócitos/metabolismo , Animais , Comunicação Celular , Humanos , Obesidade/metabolismo , Comunicação Parácrina , Transdução de Sinais , Células-Tronco/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA