Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Biol Macromol ; 253(Pt 1): 126553, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37657572

RESUMO

Several investigations have examined the involvement of free fatty acid receptor 4 (FFAR4) in metabolic disorders, but its action remains controversial. To investigate whether endogenous fibroblast growth factor 21 (FGF21)-mediated signaling controls the metabolic status in FFAR4-deficient mice, we generated FFAR4/FGF21 double knockout (DKO) mice. We also evaluated the role of FGF21 on glucose and lipid metabolism in FFAR4 KO mice fed a high-fat diet. Levels of FGF21 were significantly increased in FFAR4-deficient mice and double deletion of FGF21 and FFAR4 led to severe metabolic disorders. Additionally, FFAR4/FGF21 DKO mice displayed metabolic abnormalities that may be caused by decreased energy expenditure. Collectively, this study characterized the effects of endogenous FGF21, which acts as a master feedback regulator in the absence of FFAR4.


Assuntos
Fatores de Crescimento de Fibroblastos , Doenças Metabólicas , Animais , Camundongos , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Metabolismo Energético/genética , Glucose/metabolismo , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Fígado/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL
2.
J Cancer Res Clin Oncol ; 149(18): 16931-16946, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37698682

RESUMO

PURPOSE: Metformin has been used clinically for more than six decades. Over time, numerous remarkable effects of metformin beyond the clinic have been discovered and discussed. Metformin has been shown to have a favorable impact on cancer therapy in addition to its clinically recognized hypoglycemic effect. However, the antitumor efficacy of metformin in humans has not been clearly demonstrated yet. Hence, a systematic analysis of the existing trials is necessary. METHODS: Here, we retrieved clinical trials from the Clinical Trials.gov database to overview the clinical development of metformin for the treatment of cancer, analyze existing clinical results, and summarize some promising applications for specific cancer therapies. RESULTS: The potential application of metformin contains three directions: Firstly, improvement of metabolic factors associated with treatment effects, such as insulin resistance and peripheral neuropathy. Secondly, in combination with immune checkpoint blockade effects. Finally, use it for the endocrine treatment of hormone-dependent cancers. CONCLUSION: Although the outcomes of metformin as a repurposed agent in some trials have been unsatisfactory, it still has the potential to be used in select cancer therapy settings.


Assuntos
Resistência à Insulina , Metformina , Neoplasias , Humanos , Metformina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Neoplasias/tratamento farmacológico
3.
Biochem Biophys Res Commun ; 605: 134-140, 2022 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-35325655

RESUMO

Obesity and associated complications are becoming a pandemic. Inhibiting fatty acid synthesis and elongation is an important intervention for the treatment of obesity. Despite intensive investigations, many potential therapeutic targets have yet to be discovered. In this study, decreased expression of Hacd2 (a newly found enzyme in fatty acid elongation) was found in HFD induced mice and loss of Hacd2 expression in the liver protected mice against HFD induced obesity as well as associated fatty liver disease and diabetes. Additionally, further study indicated that hepatic HACD2 deficiency increased energy expenditure by upregulating the transcription of thermogenic programming genes. Our results suggest that HACD2 may be a promising therapeutic target for the management of obesity and associated metabolic diseases.


Assuntos
Intolerância à Glucose , Resistência à Insulina , Animais , Coenzima A/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Intolerância à Glucose/genética , Hidroliases/metabolismo , Resistência à Insulina/fisiologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo
4.
Adipocyte ; 11(1): 47-55, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34957917

RESUMO

Retinoic acid (RA), a bioactive metabolite of vitamin A, has shown therapeutic effects in liver disease, and its effect in improving non-alcoholic fatty liver disease (NAFLD) is associated with the inhibition of adipogenesis in the white adipose tissue (WAT) and fatty acid oxidation induction in the liver. However, the major target organ of RA is unknown. We performed chronic administration of RA in high-fat diet (HFD)-induced NAFLD mice. Further, hepatic and adipose cells were used to study the direct effect of RA on lipid metabolism. In addition, qRT-PCR was performed to examine differential gene expression in mouse adipose tissue. RA administration ameliorated NAFLD in HFD-induced obese mice and increased mouse energy expenditure. Although RA had therapeutic effects on liver histology and lipid accumulation, it did not directly affect lipid metabolism in HepG2 cells. In contrast, RA reduced the weight of several adipose tissues and improved lipid accumulation in OP9 cells. In addition, RA upregulated genes responsible for fatty acid oxidation and thermogenesis in three different WATs. Our work suggests that the liver may not be the main target organ of RA during NAFLD treatment. WAT browning induced by RA may be the primary contributor towards the amelioration of NAFLD in HFD-induced obese mice.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Tretinoína , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Termogênese , Tretinoína/metabolismo , Tretinoína/farmacologia
5.
Cancer Lett ; 526: 193-204, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843864

RESUMO

Low in dietary ω3 polyunsaturated fatty acid (PUFA) consumption has been associated with increased incidence of cancers. Many basic and clinical studies have been conducted over the last several decades. We previously reviewed multi-targeted therapy of cancer by omega-3 fatty acids in 2008, and since hundreds of new clinical trials are being conducted to validate the effectiveness of ω3 PUFA in cancer therapy. Because of the availability of such large amount of clinical trial data, in this update we summarize clinical data, sort out trials that show promising results, and discuss potential mechanism(s) responsible for the clinical outcomes. It appears that ω3 PUFA mainly affects cancer-associated symptoms, namely cachexia, inflammation, neuropathy, post operative complications and quality of life. Mechanisms responsible for these effects are possible regulation of skeletal muscle protein turnover, inflammatory response and neuron cell survive by ω3 PUFA.


Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Neoplasias/tratamento farmacológico , Ácidos Graxos Ômega-3/farmacologia , Humanos , Qualidade de Vida
6.
Neoplasia ; 24(2): 86-97, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34954451

RESUMO

The excessive accumulation of saturated fatty acids and cholesterol have been linked to prostate cancer (Pca). Here, we found that lipoproteins, apolipoproteins, triglycerides and free fatty acids are significantly higher in the peripheral blood of prostate cancer patients than in non-cancer patients. Furthermore, the expression of ACC1, FASN and HMGCR is significantly higher in prostate cancer tissues than that in non-cancer tissues, and positively correlated with the gleason score. Using genetically engineered mouse models, we found that in a mouse model of high grade prostatic intraneoplasia (HGPIN), a combination of fatty acid synthase (FASN) overexpression and cholesterol efflux pump (Abca1) knockout resulted in the progression of prostatic intraneoplasia (PIN) to invasive PCa with 100% penetrance, as well as an increase in prostate cancer stem cell (PCSC)population, accompanied by activation of PGE2 and TGF-ß signaling pathway. Our study suggests that the steady rise in prostate cancer incidence and mortality among Chinese population during the last several decades may be attribute to a combinational effect of fatty acid and cholesterol, and reduction in dietary fat and cholesterol intake could slow down the progression from occult lesions to prostate cancer.


Assuntos
Colesterol/metabolismo , Ácidos Graxos/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Animais , Biomarcadores , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Técnicas de Silenciamento de Genes , Humanos , Metabolismo dos Lipídeos , Masculino , Camundongos , Neoplasias da Próstata/etiologia , Transdução de Sinais
7.
Biomolecules ; 11(6)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201030

RESUMO

The association between intratumoral cholesteryl ester (CE) and tumor progression has been reported previously. The objective of our study was to investigate a causal effect of CE on mammary tumor progression. Using MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice and breast tumor cell MCF-7, we show that both exogenous and endogenous CE can increase mammary tumor growth, that CE upregulates the AKT/mTOR pathway, and that CE synthesis blockade suppresses this signaling pathway. Our data suggest that SOAT1, a sterol O-acyltransferase, may be a potential target for the treatment of breast cancer.


Assuntos
Ésteres do Colesterol/metabolismo , Neoplasias Mamárias Animais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Esterol O-Aciltransferase/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Ésteres do Colesterol/genética , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-akt/genética , Esterol O-Aciltransferase/genética , Serina-Treonina Quinases TOR/genética
8.
Nutr Cancer ; 72(4): 696-707, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31352802

RESUMO

Kudingcha is implicated in alleviating metabolic disorders in traditional Chinese medicine. However, the role of Kudingcha, one of the Ligustrum robustum species, in metabolic regulations and its antitumor activity in triple-negative breast cancer (TNBC) remains to be determined. Two breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Kudingcha treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics and western blot analysis. In this study, we found that aqueous extract of Kudingcha dose dependently inhibited cell growth and induced apoptosis in vitro and in vivo. Moreover, Kudingcha supplementation significantly reduced cancer metastasis. Kudingcha significantly inhibited glycolysis and glutamine metabolism. In addition, we demonstrated that the antitumor effects of Kudingcha were dependent on ROS production, which was increased by ß-oxidation and oxidative phosphorylation. These findings provide a novel potential benefit of Kudingcha from targeting the cancer metabolism.


Assuntos
Apoptose/efeitos dos fármacos , Ligustrum , Metástase Neoplásica/prevenção & controle , Extratos Vegetais/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Bebidas , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal , Feminino , Glicólise/efeitos dos fármacos , Humanos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Biochem Biophys Res Commun ; 512(2): 196-201, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30879764

RESUMO

G-protein coupled receptor 120 (GPR120 or FFAR4) functions as a receptor for free fatty acids and plays a critical role in lipid metabolism. Studies have shown a close relationship between GDM and lipid metabolism disorders, whether GPR120 participates in the metabolic regulation of GDM remains unclear. In this study, 29 women with GDM and 33 normal pregnant women were enrolled. Lipid profiles were determined by lipidomics, expression of GPR120 and FGF21 was measured in the white blood cells, and regulation of FGF21 by GPR120 was investigated in THP-1 cells as well as human peripheral blood monocytes. Lipidomics reveal altered lipid metabolism in patients with GDM. The expression of both GPR120 and FGF21 is significantly higher in the GDM than in the control at the 32nd and 37th weeks of pregnancy, but the differences disappear by the 2nd day post-delivery. Generally positive correlations are found between the total amount of lipids and expression levels of GPR120 and FGF21 in GDM patients. FGF21 expression is induced by GPR120 activation in THP-1 cells and WBCs. GPR120 may act as a metabolic regulator, through the induction of FGF21, to control lipid metabolism, and GDM patients may manifest a GPR120 insensitivity.


Assuntos
Diabetes Gestacional/metabolismo , Metabolismo dos Lipídeos , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Linhagem Celular , Células Cultivadas , Diabetes Gestacional/genética , Feminino , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Leucócitos/metabolismo , Gravidez , RNA Mensageiro/análise , RNA Mensageiro/genética , Receptores Acoplados a Proteínas G/genética , Regulação para Cima , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...