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1.
Res Vet Sci ; 126: 207-212, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31610471

RESUMO

To explore the effect of epigenetic modification on the differentiation of goat adipose-derived stem cells in vitro, we used two common epigenetic modification inhibitors, trichostatin A and vorinostat, to treat cashmere goat adipose-derived stem cells and induce adipocyte differentiation. The results showed that trichostatin A and vorinostat changed the relative amounts of H3K9 acetylation and dimethylation in the upstream sequence of PPARG, increased peroxisome proliferator-activated receptor gamma (PPARG) transcription before differentiation and then promoted adipocyte differentiation, and regulated the expression of adipocyte-specific genes. We conclude that adipocyte differentiation is regulated dynamically by different histone modifications. The areas of acetylation and demethylation changed by trichostatin A and vorinostat are the basis for further research on the mechanism of PPARG promoter to regulate adipocytes differentiation and provide research theroies for using adipose-derived stem cells as donor to produce transgenic animals to improve meat quality improvement.


Assuntos
Adipogenia/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Cabras/fisiologia , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Vorinostat/farmacologia , Acetilação/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Animais , Metilação/efeitos dos fármacos , PPAR gama/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/fisiologia
2.
Life Sci ; 239: 116897, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31644894

RESUMO

AIMS: Lansoprazole (LPZ) is one of the most commonly prescribed drugs for treatment of acid-related diseases, and it is increasingly recognized for its potential application as an anti-diabetic therapy. Although LPZ target tissues remain poorly understood, possible sites of action include adipose tissue. In this study, we assessed effects of LPZ on adipocyte differentiation and function by using 3T3-L1 preadipocytes and HFD-induced obesity mice as an in vitro and in vivo model, respectively. MAIN METHODS: Oil red O staining and intracellular triacylglycerol content were used to determine lipid accumulation. Glucose uptake was performed to measure mature adipocyte function. Expression of adipocyte genes was determined by qRT-PCR and immunoblotting. KEY FINDINGS: LPZ has dual effects on differentiation of 3T3-L1 cells. At low concentrations, LPZ enhanced adipocyte differentiation via induction of PPARγ and C/EBPα, two master adipogenic transcription factors, as well as lipogenic proteins, ACC1 and FASN. Increasing of adipocyte number subsequently increased basal and insulin-stimulated glucose uptake, and expression of Glut4 mRNA. Conversely, high concentrations of LPZ strongly inhibited differentiation and expression of PPARγ and C/EBPα, and maintained expression of preadipocytes markers, ß-catenin and Pref-1. Inhibition of adipogenesis by LPZ reduced mature adipocyte number, Glut4 mRNA expression and insulin-stimulated glucose uptake. In addition, treatment with LPZ at 200 mg/kg significantly reduced body weight gain and total fat mass in HFD-induced obese mice. SIGNIFICANCE: These results indicate that effects of LPZ on adipocyte differentiation are dependent on concentration and are correlated with PPARγ and C/EBPα.


Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Lansoprazol/metabolismo , Células 3T3-L1 , Adipócitos/fisiologia , Adipogenia/efeitos dos fármacos , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Dieta Hiperlipídica , Transportador de Glucose Tipo 4/metabolismo , Insulina/metabolismo , Lansoprazol/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , PPAR gama/metabolismo , Triglicerídeos/metabolismo
3.
Mol Cell ; 76(5): 811-825.e14, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31628041

RESUMO

Physical contact between organelles is vital to the function of eukaryotic cells. Lipid droplets (LDs) are dynamic organelles specialized in lipid storage that interact physically with mitochondria in several cell types. The mechanisms coupling these organelles are, however, poorly understood, and the cell-biological function of their interaction remains largely unknown. Here, we discover in adipocytes that the outer mitochondrial membrane protein MIGA2 links mitochondria to LDs. We identify an amphipathic LD-targeting motif and reveal that MIGA2 binds to the membrane proteins VAP-A or VAP-B in the endoplasmic reticulum (ER). We find that in adipocytes MIGA2 is involved in promoting triglyceride (TAG) synthesis from non-lipid precursors. Our data indicate that MIGA2 links reactions of de novo lipogenesis in mitochondria to TAG production in the ER, thereby facilitating efficient lipid storage in LDs. Based on its presence in many tissues, MIGA2 is likely critical for lipid and energy homeostasis in a wide spectrum of cell types.


Assuntos
Adipócitos/metabolismo , Lipogênese/fisiologia , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Células 3T3 , Adipócitos/fisiologia , Animais , Células COS , Diferenciação Celular/fisiologia , Retículo Endoplasmático/metabolismo , Células HEK293 , Humanos , Gotículas Lipídicas/metabolismo , Lipogênese/genética , Proteínas de Membrana/fisiologia , Camundongos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/fisiologia , Triglicerídeos/biossíntese , Proteínas de Transporte Vesicular/metabolismo
4.
Biomed Environ Sci ; 32(8): 578-591, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31488234

RESUMO

OBJECTIVE: We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats. METHODS: In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw). RESULTS: In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity. CONCLUSION: These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.


Assuntos
Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/metabolismo , Lactobacillus plantarum/química , Obesidade/tratamento farmacológico , Probióticos/metabolismo , Proteína Desacopladora 1/metabolismo , Células 3T3 , Adipócitos/fisiologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/fisiologia , Ração Animal/análise , Animais , Fármacos Antiobesidade/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Dieta , Fermentação , Hordeum/química , Masculino , Camundongos , Obesidade/genética , Extratos Vegetais/química , Probióticos/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Proteína Desacopladora 1/genética
5.
Plast Reconstr Surg ; 144(3): 644-655, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31461020

RESUMO

BACKGROUND: Adipose-derived stem cells and ceiling culture-derived preadipocytes can be harvested from subcutaneous adipose tissue. Little is known about the epigenetic differences, which may contribute to differences in osteogenic potential, between these cell types. The purpose of this study was to address the osteogenic potential and underlying epigenetic status of adipose-derived stem cells and ceiling culture-derived preadipocytes. METHODS: Adipose-derived stem cells and ceiling culture-derived preadipocytes were cultured from abdominal subcutaneous fat tissues of four metabolically healthy, lean female patients. After 7 weeks of culture, cellular responses to osteogenic differentiation media were examined. To evaluate the osteogenic potentials of undifferentiated adipose-derived stem cells and ceiling culture-derived preadipocytes, two types of epigenetic assessment were performed using next-generation sequencing: DNA methylation assays with the Human Methylation 450K BeadChip, and chromatin immunoprecipitation assays for trimethylation of histone H3 at lysine 4. RESULTS: Human ceiling culture-derived preadipocytes showed greater osteogenic differentiation ability than did adipose-derived stem cells. In an epigenetic survey of the promoters of four osteogenic regulator genes (RUNX2, SP7, ATF4, and BGLAP), the authors found a general trend toward decreased CpG methylation and increased trimethylation of histone H3 at lysine 4 levels in ceiling culture-derived preadipocytes as compared to adipose-derived stem cells, indicating that these genes were more likely to be highly expressed in ceiling culture-derived preadipocytes. CONCLUSIONS: The surveyed epigenetic differences between adipose-derived stem cells and ceiling culture-derived preadipocytes were consistent with the observed differences in osteogenic potential. These results enhance the authors' understanding of these cells and will facilitate their further application in regenerative medicine.


Assuntos
Adipócitos/citologia , Adipócitos/fisiologia , Epigênese Genética/fisiologia , Osteogênese/fisiologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Gordura Subcutânea/citologia , Adulto , Células Cultivadas , Feminino , Humanos , Pessoa de Meia-Idade
6.
Int J Mol Sci ; 20(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340593

RESUMO

Normothermic machine perfusion (NMP) of kidneys offers the opportunity to perform active interventions, such as the addition of mesenchymal stromal cells (MSCs), to an isolated organ prior to transplantation. The purpose of this study was to determine whether administering MSCs to kidneys during NMP is feasible, what the effect of NMP is on MSCs and whether intact MSCs are retained in the kidney and to which structures they home. Viable porcine kidneys were obtained from a slaughterhouse. Kidneys were machine perfused during 7 h at 37 °C. After 1 h of perfusion either 0, 105, 106 or 107 human adipose tissue derived MSCs were added. Additional ex vivo perfusions were conducted with fluorescent pre-labelled bone-marrow derived MSCs to assess localisation and survival of MSCs during NMP. After NMP, intact MSCs were detected by immunohistochemistry in the lumen of glomerular capillaries, but only in the 107 MSC group. The experiments with fluorescent pre-labelled MSCs showed that only a minority of glomeruli were positive for infused MSCs and most of these glomeruli contained multiple MSCs. Flow cytometry showed that the number of infused MSCs in the perfusion circuit steeply declined during NMP to approximately 10%. In conclusion, the number of circulating MSCs in the perfusate decreases rapidly in time and after NMP only a small portion of the MSCs are intact and these appear to be clustered in a minority of glomeruli.


Assuntos
Rastreamento de Células/métodos , Glomérulos Renais/ultraestrutura , Transplante de Rim , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Perfusão/métodos , Adipócitos/citologia , Adipócitos/fisiologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Diferenciação Celular , Corantes Fluorescentes/metabolismo , Humanos , Glomérulos Renais/cirurgia , Transplante de Células-Tronco Mesenquimais/instrumentação , Células-Tronco Mesenquimais/fisiologia , Microscopia de Fluorescência , Preservação de Órgãos/métodos , Compostos Orgânicos/metabolismo , Perfusão/instrumentação , Suínos , Temperatura Ambiente , Transplante Heterólogo
8.
Int J Mol Sci ; 20(12)2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31248114

RESUMO

Sirt1 (Sirtuin 1), AMPK (AMP-activated protein kinase), and eNOS (endothelial nitric oxide synthase) modulate hepatic energy metabolism and inflammation and play a major role in the development of NASH. Cyclic nucleotide phosphodiesterases (PDEs) play an important role in signal transduction by modulating intracellular levels of cyclic nucleotides. We previously found the PDE5 inhibitor sildenafil to synergize with leucine and leucine-metformin combinations in preclinical studies of NASH and obesity. However, efficacy is diminished at higher sildenafil concentrations. Herein, we have successfully modeled the U-shaped sildenafil dose-response in vitro and utilized this model to assess potential mechanisms of this dose-response relationship. Adipocytes and liver cells were treated with leucine (0.5 mM) and different concentrations of sildenafil (1 nM to 100 µM). cAMP, cGMP, and P-AMPK protein expression were used to demonstrate the biphasic response for increasing concentrations of sildenafil. The reversal with higher sildenafil levels was blunted by PDE2 inhibition. These data indicate that sildenafil-mediated increases in cGMP inhibits PDE3 at lower concentrations, which increases cAMP. However, further increases in cGMP from higher sildenafil concentrations activate PDE2 and consequently decrease cAMP, which demonstrates crosstalk between cAMP and cGMP via PDE2, PDE3, and PDE5. These changes in cAMP concentration are further reflected in downstream effects, including AMPK activation.


Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/fisiologia , Transdução de Sinais/efeitos dos fármacos , Citrato de Sildenafila/farmacologia , Animais , Linhagem Celular , Metabolismo Energético/efeitos dos fármacos , Humanos , Camundongos
9.
Int J Mol Sci ; 20(12)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31208008

RESUMO

Excessive abdominal fat deposition is an issue with general concern in broiler production, especially for Chinese native chicken breeds. A high-fat diet (HFD) can induce body weight gained and excessive fat deposition, and genes and pathways participate in fat metabolism and adipogenesis would be influenced by HFD. In order to reveal the main genes and pathways involved in chicken abdominal fat deposition, we used HFD and normal diet (ND) to feed a Chinese native chicken breed, respectively. Results showed that HFD can increase abdominal fat deposition and induce adipocyte hypertrophy. Additionally, we used RNA-sequencing to identify the differentially expressed genes (DEGs) between HFD and ND chickens in liver and abdominal fat. By analyzed these DEGs, we found that the many DEGs were enriched in fat metabolism related pathways, such as peroxisome proliferator-activated receptor (PPAR) signaling, fat digestion and absorption, extracellular matrix (ECM)-receptor interaction, and steroid hormone biosynthesis. Notably, the expression of insulin-like growth factor II mRNA binding protein 1 (IGF2BP1), which is a binding protein of IGF2 mRNA, was found to be induced in liver and abdominal fat by HFD. Ectopic expression of IGF2BP1 in chicken liver-related cell line Leghorn strain M chicken hepatoma (LMH) cell revealed that IGF2BP1 can regulate the expression of genes associated with fatty acid metabolism. In chicken preadipocytes (ICP cell line), we found that IGF2BP1 can promote adipocyte proliferation and differentiation, and the lipid droplet content would be increased by overexpression of IGF2BP1. Taken together, this study provides new insights into understanding the genes and pathways involved in abdominal fat deposition of Chinese native broiler, and IGF2BP1 is an important candidate gene for the study of fat metabolism and adipogenesis in chicken.


Assuntos
Adipogenia/genética , Galinhas/genética , Transcriptoma , Gordura Abdominal/metabolismo , Adipócitos/metabolismo , Adipócitos/fisiologia , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Linhagem Celular , Proliferação de Células , Ácidos Graxos/metabolismo , Feminino , Gotículas Lipídicas/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
10.
Int J Mol Sci ; 20(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146351

RESUMO

Evaluating cell migration after cell-based treatment is important for several disorders, including osteoarthritis (OA), as it might influence the clinical outcome. This research explores migrating expanded-adipose stromal cells (ASCs) and adipose niches after enzymatic and mechanical processes. Bilateral anterior cruciate ligament transection induced a mild grade of OA at eight weeks in adult male New Zealand rabbits. ASCs, enzymatic stromal vascular fraction (SVF), and micro fragmented adipose tissue (MFAT) were intra-articularly injected in the knee joint. Assessments of cell viability and expression of specific markers, including CD-163 wound-healing macrophages, were done. Cell migration was explored through labelling with PKH26 dye at 7 and 30 days alongside co-localization analyses for CD-146. All cells showed good viability and high percentages of CD-90 and CD-146. CD-163 was significantly higher in MFAT compared to SVF. Distinct migratory potential and time-dependent effects were observed among cell-based treatments. At day 7, both ASCs and SVF migrated towards synovium, whereas for MFAT versus cartilage, a different migration pattern was noticed at day 30. The long-term distinct cell migration of ASCs, SVF, and MFAT open interesting clinical insights on their potential use for OA treatment. Moreover, the highest expression of CD-163 in MFAT, rather than SVF, might have an important role in directly mediating cartilage tissue repair responses.


Assuntos
Adipócitos/transplante , Osteoartrite do Joelho/terapia , Regeneração , Transplante de Células-Tronco/métodos , Adipócitos/citologia , Adipócitos/fisiologia , Animais , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , Movimento Celular , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Cultura Primária de Células/métodos , Coelhos
11.
Biol Pharm Bull ; 42(6): 968-976, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155593

RESUMO

Previously, we reported that adenosine N1-oxide (ANO), which is found in royal jelly, inhibited the secretion of inflammatory mediators by activated macrophages and reduced lethality in lipopolysaccharide (LPS)-induced endotoxin shock. Here, we examined the regulatory mechanisms of ANO on the release of pro-inflammatory cytokines, with a focus on the signaling pathways activated by toll-like receptor (TLR)4 in response to LPS. ANO inhibited both tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion from LPS-stimulated RAW264.7 cells without affecting cell proliferation. In this response, phosphorylation of mitogen-activated protein kinase (MAPK) family members (extracellular signal-regulated kinase (ERK)1/2, p38 and SAPK/c-Jun N-terminal kinase (JNK)) and nuclear factor-κB (NF-κB) p65 was not affected by treatment with ANO. In contrast, phosphorylation of Akt (Ser473) and its downstream molecule glycogen synthase kinase-3ß (GSK-3ß) (Ser9) was up-regulated by ANO, suggesting that ANO stimulated GSK-3ß phosphorylation via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. The phosphorylation of GSK-3ß on Ser9 has been shown to negatively regulate the LPS-induced inflammatory response. Activation of PI3K/Akt signaling pathway has also been implicated in differentiation of mesenchymal stem cells into osteoblasts and adipocytes. As expected, ANO induced alkaline phosphatase activity and promoted calcium deposition in a mouse pre-osteoblastic MC3T3-E1 cell line. The ANO-induced differentiation into osteoblasts was abrogated by coincubation with Wortmannin. Furthermore, ANO promoted insulin/dexamethasone-induced differentiation of mouse 3T3-L1 preadipocytes into adipocytes at much lower concentrations than adenosine. The protective roles of PI3K/Akt/GSK-3ß signaling pathway in inflammatory disorders have been well documented. Our data suggest that ANO may serve as a potential candidate for the treatment of inflammatory disorders. Promotion of osteogenic and adipocyte differentiation further suggests its application for regenerative medicine.


Assuntos
Adenosina/análogos & derivados , Adipócitos/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Óxidos N-Cíclicos/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adenosina/farmacologia , Adipócitos/fisiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Osteogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
12.
Res Vet Sci ; 125: 71-81, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152923

RESUMO

Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system that destroys oligodendrocytes. This work aims to evaluate the treatment of experimentally induced MS in dogs using laser activated non-expanded adipose derived stem cells. The results showed amelioration of the clinical signs over time confirmed by the resolution of the previous lesions on MRI. Positive migration of the injected cells to the site of lesion, increased remyelination detected by Myelin Basic Proteins, positive differentiation into Olig2 positive oligodendrocytes, prevented the glial scar formation and restored axonal architecture. The study concluded that treatment using laser activated stem cells holds a promising therapeutic option for treatment of MS in a canine model.


Assuntos
Adipócitos/fisiologia , Tecido Adiposo/citologia , Células-Tronco Mesenquimais/fisiologia , Esclerose Múltipla/terapia , Oligodendroglia/fisiologia , Adipócitos/efeitos da radiação , Tecido Adiposo/efeitos da radiação , Animais , Diferenciação Celular , Modelos Animais de Doenças , Cães , Imuno-Histoquímica/veterinária , Lasers , Imagem por Ressonância Magnética/veterinária , Células-Tronco Mesenquimais/efeitos da radiação , Proteína Básica da Mielina , Fator de Transcrição 2 de Oligodendrócitos , Oligodendroglia/efeitos da radiação , Distribuição Aleatória , Medula Espinal/patologia , Medula Espinal/ultraestrutura
13.
J Infect Public Health ; 12(5): 726-732, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31133421

RESUMO

BACKGROUND: Investigation for a naturally occurring anti-obesity drug has become the need of society all over the world. Betulinic acid (BA) is a lupane-type pentacyclic triterpene and is sourced from various organisms. This high potential biologically active molecule is reported to have anti-obesity effect. In this study, we report the molecular mechanism of action of BA that underlies anti-obesity activity and also an improved method of its isolation common teak tree. METHODS: Mouse pre-adipocyte cells were used to develop hyperlipidemic conditions in vitro. Change in expression of genes associated to adipogenesis was checked using quantitative real-time PCR (qPCR). Co-factor specificity of PPAR gamma was analyzed through immune precipitation and immunoblot. RESULTS: Betulinic acid was found to be effective in reducing the lipid content in 3T3L1 cells. Level of PPAR gamma and LXR alpha was reduced in connection to reduced adipogenesis. Change in steroid responsive co-activators (SRCs) during BA treatment proved that the compound can impart profound change in co-factor selectivity, which is crucial in determining the activity profile of PPAR gamma. BA treatment enhanced the SRC-1 interaction with PPAR gamma while reducing the levels of SRC-3. CONCLUSION: Present study has proved that betulinic acid, a promising candidate in anti-obesity drug development, has potential in regulating the activity of PPAR gamma through co-factor modulation.


Assuntos
Adipócitos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Coativador 1 de Receptor Nuclear/metabolismo , PPAR gama/metabolismo , Triterpenos/farmacologia , Adipócitos/fisiologia , Adipogenia/efeitos dos fármacos , Animais , Linhagem Celular , Lamiaceae/química , Camundongos , Coativador 1 de Receptor Nuclear/genética , Obesidade/tratamento farmacológico , PPAR gama/genética
14.
J Anim Sci ; 97(6): 2644-2657, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30959518

RESUMO

Sequencing technology, especially next-generation RNA sequencing, has greatly facilitated the identification and annotation of long noncoding RNAs (lncRNAs). In mammals, a large number of lncRNAs have been identified, which regulate various biological processes. An increasing number of lncRNAs have been identified which could function as key regulators of adipogenesis (adipocyte formation), a key step of the development of adipose tissue. Because proper adipose tissue development is a key factor affecting animal growth efficiency, lean/fat ratio, and meat quality, summarizing the roles and recent advances of lncRNAs in adipogenesis is needed in order to develop strategies to effectively manage fat deposition. In this review, we updated lncRNAs contributed to the regulation of adipogenesis, focusing on their roles in fat development of farm animals.


Assuntos
Adipogenia/genética , Tecido Adiposo/metabolismo , Adiposidade/genética , Animais Domésticos/genética , Carne/normas , RNA Longo não Codificante/genética , Adipócitos/fisiologia , Animais , Composição Corporal/genética , Crescimento e Desenvolvimento , Sequenciamento de Nucleotídeos em Larga Escala , Células-Tronco/fisiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-30946893

RESUMO

INTRODUCTION: Adipose tissues release adipokines, which regulate energy intake and expenditure. G protein-coupled receptors (GPCRs) and associated signaling pathways in adipocytes are potentially important drug targets for conditions with disturbed energy metabolism. METHODS: The aim of the current study was to compare signaling of endogenously expressed GPCRs between primary preadipocytes and differentiated adipocytes using a novel state-of-the-art unbiased method that measures dynamic mass redistribution (DMR) in real-time. Adrenergic agonists were chosen since they control adipocyte functions such as lipolysis and glycogenolysis. RESULTS: Isoprenaline (ISO) and phenylephrine (PE) elicited concentration-dependent responses in preadipocytes and differentiated adipocytes. The effect of ISO was cholera toxin (CTX)-sensitive, indicating it is Gs-dependent. The effect could also be blocked by propranolol proving the signal is mediated through ß-adrenergic receptors. The signaling resulting from PE stimulation was completely abolished by the Gq/11-selective inhibitor FR900359 and CTX in preadipocytes but surprisingly became FR900359-insensitive but remained CTX-sensitive in differentiated adipocytes. The use of prazosin and propranolol revealed that the PE-response in differentiated adipocytes had a ß-adrenergic receptor component to it. In addition, we tested the bone-derived peptide osteocalcin, which did not result in DMR changes in preadipocytes or differentiated adipocytes. DISCUSSION: In conclusion, this study for the first time demonstrates that DMR assays can be used to assess signaling in differentiated adipocytes. This platform can serve as a tool for future drug screening in primary adipocytes. Furthermore, this study illustrates that PE-induced effects on adipocytes vary by developmental stage and are not as selective as originally thought.


Assuntos
Adipócitos/metabolismo , Diferenciação Celular/fisiologia , Receptores Adrenérgicos beta/metabolismo , Transdução de Sinais/fisiologia , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Agonistas Adrenérgicos beta/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Isoproterenol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteocalcina/metabolismo , Prazosina/farmacologia , Propranolol/farmacologia , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Nutrients ; 11(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939853

RESUMO

Type 2 diabetes is a complex, heterogeneous, and polygenic disease. Currently, available drugs for treating type 2 diabetes predominantly include sulfonylureas, α-glucosidase inhibitors, and biguanides. However, long-term treatment with these therapeutic drugs is often accompanied by undesirable side effects, which have driven interest in the development of more effective and safer antidiabetic agents. To address the urgent need for new chemical solutions, we focused on the analysis of structurally novel and/or biologically new metabolites produced by insect-associated microbes as they have recently been recognized as a rich source of natural products. Comparative LC/MS-based analysis of Actinomadura sp. RB99, isolated from a fungus-growing termite, led to the identification of the type II polyketide synthase-derived fridamycin A. The structure of fridamycin A was confirmed by ¹H NMR data and LC/MS analysis. The natural microbial product, fridamycin A, was examined for its antidiabetic properties in 3T3-L1 adipocytes, which demonstrated that fridamycin A induced glucose uptake in 3T3-L1 cells by activating the AMP-activated protein kinase (AMPK) signaling pathway but did not affect adipocyte differentiation, suggesting that the glucose uptake took place through activation of the AMPK signaling pathway without inducing adipogenesis. Our results suggest that fridamycin A has potential to induce fewer side effects such as weight gain compared to rosiglitazone, a commonly used antidiabetic drug, and that fridamycin A could be a novel potential therapeutic candidate for the management of type 2 diabetes.


Assuntos
Adipócitos/efeitos dos fármacos , Antraquinonas/farmacologia , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Células 3T3-L1 , Adipócitos/fisiologia , Adipogenia/efeitos dos fármacos , Animais , Antraquinonas/química , Antraquinonas/isolamento & purificação , Transporte Biológico/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Camundongos , Estrutura Molecular
17.
Nat Commun ; 10(1): 1809, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-31000713

RESUMO

Krüppel-associated box zinc finger proteins (KZFPs) constitute the largest family of mammalian transcription factors, but most remain completely uncharacterized. While initially proposed to primarily repress transposable elements, recent reports have revealed that KFZPs contribute to a wide variety of other biological processes. Using murine and human in vitro and in vivo models, we demonstrate here that one poorly studied KZFP, ZFP30, promotes adipogenesis by directly targeting and activating a retrotransposon-derived Pparg2 enhancer. Through mechanistic studies, we further show that ZFP30 recruits the co-regulator KRAB-associated protein 1 (KAP1), which, surprisingly, acts as a ZFP30 co-activator in this adipogenic context. Our findings provide an understanding of both adipogenic and KZFP-KAP1 complex-mediated gene regulation, showing that the KZFP-KAP1 axis can also function in a non-repressive manner.


Assuntos
Adipogenia/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/metabolismo , Proteína 28 com Motivo Tripartido/metabolismo , Dedos de Zinco/fisiologia , Células 3T3 , Adipócitos/fisiologia , Animais , Biologia Computacional , Proteínas de Ligação a DNA/genética , Elementos Facilitadores Genéticos , Feminino , Regulação da Expressão Gênica/fisiologia , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , PPAR gama/genética , Regiões Promotoras Genéticas/genética , Retroelementos/genética , Fatores de Transcrição/genética
18.
Nutrients ; 11(4)2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-31013923

RESUMO

Over the past decades, obesity has become a rising health problem as the accessibility to high calorie, low nutritional value food has increased. Research shows that some bioactive components in fruits and vegetables, such as carotenoids, could contribute to the prevention and treatment of obesity. Some of these carotenoids are responsible for vitamin A production, a hormone-like vitamin with pleiotropic effects in mammals. Among these effects, vitamin A is a potent regulator of adipose tissue development, and is therefore important for obesity. This review focuses on the role of the provitamin A carotenoid ß-carotene in human health, emphasizing the mechanisms by which this compound and its derivatives regulate adipocyte biology. It also discusses the physiological relevance of carotenoid accumulation, the implication of the carotenoid-cleaving enzymes, and the technical difficulties and considerations researchers must take when working with these bioactive molecules. Thanks to the broad spectrum of functions carotenoids have in modern nutrition and health, it is necessary to understand their benefits regarding to metabolic diseases such as obesity in order to evaluate their applicability to the medical and pharmaceutical fields.


Assuntos
Obesidade/tratamento farmacológico , beta Caroteno/uso terapêutico , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Animais , Dieta , Humanos , beta-Caroteno 15,15'-Mono-Oxigenase/metabolismo
19.
Clin Calcium ; 29(3): 374-379, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30814384

RESUMO

Epigenome, a record of the chemical changes to the DNA and histone proteins of an organism, is dynamically altered by environmental conditions and thus contributes to an adaptive mechanism for the given environmental stress. Among them, the cold environment is life-threatening to homeothermic animals. To combat, they induce thermogenic gene expression such as Ucp1 against cold stress. We recently revealed dual roles for the histone demethylase JMJD1A as a mediator of both acute and chronic thermogenic responses to cold stress, in two distinct thermogenic tissues, and through two distinct molecular mechanisms.


Assuntos
Adipócitos/fisiologia , Temperatura Baixa , Epigenômica , Termogênese , Animais
20.
J Craniofac Surg ; 30(3): 730-735, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30817525

RESUMO

Mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes, each of which is important for musculoskeletal tissue regeneration and repair. Reconstruction and healing of bony defects remains a major clinical challenge. Even as surgical practices advance, some severe cases of bone loss do not yield optimal recovery results. New techniques involving implantation of stem cells and tissue-engineered scaffolds are being developed to help improve bone and cartilage repair. The invasiveness and low yield of harvesting MSCs from the bone marrow (BMSCs) has led to the investigation of alternatives, including adipose-derived mesenchymal stem cells (ASCs). A review of the literature yielded several studies concerning the use of BMSCs and ASCs for the treatment of bone defects in both in vitro and in vivo models. Although both ASCs and BMSCs have demonstrated bone regenerative capabilities, BMSCs have outperformed ASCs in vitro. Despite these in vitro study findings, in vivo study results remain variable. Analysis of the literature seems to conclude there is no significant difference between bone regeneration using ASCs or BMSCs in vivo. Improved study design and standardization may enhance the application of these studies to patient care in the clinical setting.


Assuntos
Regeneração Óssea/fisiologia , Células-Tronco Mesenquimais/fisiologia , Adipócitos/fisiologia , Tecido Adiposo , Animais , Transplante de Medula Óssea/métodos , Transplante de Medula Óssea/tendências , Diferenciação Celular/fisiologia , Condrócitos/fisiologia , Previsões , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/tendências , Células-Tronco Mesenquimais/citologia , Modelos Animais , Osteoblastos/fisiologia , Tecidos Suporte
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