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1.
Anim Sci J ; 91(1): e13462, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33190272

RESUMO

Several microRNAs (miRNAs) have been identified to play roles in adipocyte differentiation. However, little is known about their involvement in the differentiation of ovine intramuscular adipocytes. Here, the role of one such miRNA, miR-340-5p, in ovine adipocyte differentiation was investigated. Stromal vascular (SV) cells were isolated from skeletal muscle tissues of 1-month-old lambs and induced to differentiate into mature adipocytes. miRNA mimics and inhibitors were used for miR-340-5p overexpression and knockdown assays. For overexpression and knockdown of activating transcription factor 7 (ATF7), lentivirus infection was performed. Luciferase reporter assay was performed to determine the relationship between miR-340-5p and ATF7. The expression of adipogenesis marker genes, PPARγ, C/EBPα, FABP4, ADIPOQ, and ACC, and formation of lipid droplets were detected after the overexpression and inhibition of miR-340-5p, or upon overexpression or knockdown of ATF7. miR-340-5p inhibited the expression of the marker genes and the formation of lipid droplets. ATF7 positively regulated the expression of the marker genes and the formation of lipids. Thus, ATF7 is the target of miR-340-5p in sheep. Overall, these findings indicate that miR-340-5p acts as an inhibitor of the differentiation of intramuscular adipocytes by targeting ATF7. Our study provides a new theoretical basis for improving sheep meat quality.


Assuntos
Fatores Ativadores da Transcrição/genética , Fatores Ativadores da Transcrição/metabolismo , Adipócitos/fisiologia , Adipogenia/genética , Diferenciação Celular/genética , Expressão Gênica , Metabolismo dos Lipídeos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Ovinos , Células 3T3-L1 , Animais , Células Cultivadas , Qualidade dos Alimentos , Carne , Camundongos , MicroRNAs/fisiologia , Músculos/citologia , Ligação Proteica , Células Estromais/metabolismo
2.
Hum Cell ; 33(4): 974-989, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32495194

RESUMO

Adipose-derived stem cells (ASCs) and dedifferentiated fat (DFAT) cells are alternative cell sources in tissue engineering and regeneration because they are easily obtained and exhibit multilineage differentiation. However, aging may attenuate their regenerative potential and metabolic functions. Reports characterizing DFAT cells derived from aging donors are rare, and comparisons of DNA methylation profiles between aging ASCs and DFAT cells are poorly understood. Therefore, this study aimed to characterize DFAT cells relative to ASCs derived from aging subjects and compare the DNA methylation profiles of four adipogenic genes in these cells. ASCs and DFAT cells from aging donors exhibited characteristics similar to those of stem cells, including colony formation, proliferation, and multilineage differentiation abilities. However, compared with ASCs, DFAT cells exhibited increased proliferation, smooth muscle actin alpha (SMA-α) expression and decreased cellular senescence. DNA methylation profiling of ASCs and DFAT cells by combined bisulfite restriction analysis (COBRA) demonstrated hypermethylation patterns in three potent adipogenic genes-peroxisome proliferator-activated receptor gamma 2 (PPARγ2), fatty acid-binding protein 4 (FABP4), and lipoprotein lipase (LPL)-but hypomethylation of CCAAT/enhancer binding protein alpha (C/EBPα) in the aging group. Statistically significant differences were observed between the aging group and the young group. Epigenetic regulation maintains the stability of ASCs and DFAT cells in an age-dependent manner. Our findings suggested that although the DNA methylation patterns of three adipogenic genes correlated with hypermethylation and aging, ASCs and DFAT cells exhibited cellular stability and several stem cell characteristics, offering further opportunities for personalized regeneration and energy maintenance by adipogenesis during aging.


Assuntos
Adipócitos/fisiologia , Adipogenia/genética , Tecido Adiposo/citologia , Diferenciação Celular/genética , Metilação de DNA/genética , Células-Tronco/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Células Cultivadas , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Engenharia Tecidual , Adulto Jovem
3.
Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165853, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32502648

RESUMO

Phosphatidylethanolamine N-methyltransferase (PEMT) is a small integral membrane protein that converts phosphatidylethanolamine (PE) into phosphatidylcholine (PC). It has been previously reported that, unexpectedly, PEMT deficiency protected from high-fat diet (HFD)-induced obesity and insulin resistance, pointing to a possible role of this enzyme in the regulation of adipose cell metabolism. Using mouse 3T3-L1 preadipocytes as a biological system, we demonstrate that PEMT expression is strongly increased during the differentiation of preadipocytes into mature adipose cells. Knockdown of PEMT reduced the expression of early and late adipogenic markers, inhibited lipid droplet formation, reduced triacylglycerol content and decreased the levels of leptin release from the adipocytes, suggesting that PEMT is a novel and relevant regulator of adipogenesis. Investigation into the mechanisms whereby PEMT regulates adipocyte differentiation revealed that extracellularly regulated kinases (ERK1/2) and AKT are essential factors in this process. Specifically, the activities of ERK1/2 and AKT, which are decreased during adipocyte differentiation, were elevated upon Pemt knockdown. Moreover, treatment of cells with exogenous ceramide 1-phosphate (C1P), which we reported to be a negative regulator of adipogenesis, decreased PEMT expression, suggesting that PEMT is also a relevant factor in the anti-adipogenic action of C1P. Altogether, the data presented here identify PEMT as a novel regulator of adipogenesis and a mediator of the anti-adipogenic action of C1P.


Assuntos
Adipócitos/fisiologia , Adipogenia/fisiologia , Fosfatidiletanolamina N-Metiltransferase/metabolismo , Células 3T3-L1 , Animais , Diferenciação Celular/fisiologia , Ceramidas/metabolismo , Meios de Cultura/metabolismo , Técnicas de Silenciamento de Genes , Gotículas Lipídicas/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidiletanolamina N-Metiltransferase/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Regulação para Cima
4.
Anim Genet ; 51(4): 521-530, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32400010

RESUMO

The cAMP responsive element binding protein (CREB)-regulated transcription coactivator 3 (CRTC3) is a member of the CRTC protein family and plays an important role in energy metabolism. The aim of this study was to determine if the expression of porcine CRTC3 is related to intramuscular fat (IMF) deposition and meat quality in Heigai pigs (a local fatty breed in China) and Duroc × Landrace × Yorkshire (DLY) pigs (a lean crossbred pig widely cultured in China). In addition, the effect of ectopic expression of CRTC3 on gene expression in porcine IMF adipocytes was also examined. Our results showed that Heigai pigs had lower lean percentage, thicker back fat thickness and smaller loin muscle area than DLY pigs. Compared with DLY pigs, Heigai pigs had higher marbling scores, better meat color and higher IMF contents and triglyceride concentrations. Higher levels of oxidative metabolic enzyme and expression of the slow oxidative muscle fiber-related genes were observed in longissimus dorsi muscle and psoas major muscle (P < 0.05) from Heigai pigs. Notably, CRTC3 and adipocyte-specific marker genes were highly expressed in muscle tissues of Heigai pigs. The expression of lipolysis-related genes ATGL and HSL were lower in Heigai muscles. Moreover, forced expression of CRTC3 promoted lipid accumulation and increased the expression of PPARγ, C/EBPα, leptin and FABP4 (P < 0.05), whereas it decreased the expression of ATGL and HSL in IMF adipocytes. These results suggest that CRTC3 expression is associated with lipid accumulation and IMF deposition in pigs.


Assuntos
Adipócitos/fisiologia , Expressão Gênica , Carne/análise , Sus scrofa/metabolismo , Fatores de Transcrição/genética , Animais , Cruzamento , Sus scrofa/genética , Fatores de Transcrição/metabolismo
5.
Nat Metab ; 2(5): 397-412, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32440655

RESUMO

Human thermogenic adipose tissue mitigates metabolic disease, raising much interest in understanding its development and function. Here, we show that human thermogenic adipocytes specifically express a primate-specific long non-coding RNA, LINC00473 which is highly correlated with UCP1 expression and decreased in obesity and type-2 diabetes. LINC00473 is detected in progenitor cells, and increases upon differentiation and in response to cAMP. In contrast to other known adipocyte LincRNAs, LINC00473 shuttles out of the nucleus, colocalizes and can be crosslinked to mitochondrial and lipid droplet proteins. Up- or down- regulation of LINC00473 results in reciprocal alterations in lipolysis, respiration and transcription of genes associated with mitochondrial oxidative metabolism. Depletion of PLIN1 results in impaired cAMP-responsive LINC00473 expression and lipolysis, indicating bidirectional interactions between PLIN1, LINC00473 and mitochondrial oxidative functions. Thus, we suggest that LINC00473 is a key regulator of human thermogenic adipocyte function, and reveals a role for a LincRNA in inter-organelle communication and human energy metabolism.


Assuntos
Adipócitos/fisiologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Termogênese/genética , Termogênese/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comunicação Celular/genética , Comunicação Celular/fisiologia , Núcleo Celular/metabolismo , Células Cultivadas , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético/genética , Metabolismo Energético/fisiologia , Ácidos Graxos não Esterificados/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Gotículas Lipídicas , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/metabolismo , Consumo de Oxigênio/genética , Consumo de Oxigênio/fisiologia , Perilipina-1/deficiência , Perilipina-1/genética , Proteína Desacopladora 1/biossíntese , Proteína Desacopladora 1/genética , Adulto Jovem
6.
Obes Facts ; 13(2): 130-143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32325455

RESUMO

BACKGROUND: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. OBJECTIVES: The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5-52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1-23.9]). METHODS: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3-5 as well as their intron-exon boundaries was performed using automatic sequencing. RESULTS: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. CONCLUSION: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity.


Assuntos
Adipócitos Marrons/fisiologia , Adipócitos/fisiologia , Transdiferenciação Celular/genética , Fibronectinas/genética , Obesidade Mórbida/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Polimorfismo de Nucleotídeo Único , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/fisiologia , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Metabolismo Energético/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Mutação de Sentido Incorreto , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Adulto Jovem
7.
Curr HIV/AIDS Rep ; 17(2): 138-150, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32072466

RESUMO

PURPOSE OF REVIEW: The proportion of overweight and obese persons with HIV (PWH) has increased since the introduction of antiretroviral therapy (ART). We aim to summarize recent literature on risks of weight gain, discuss adipose tissue changes in HIV and obesity, and synthesize current understanding of how excess adiposity and HIV contribute to metabolic complications. RECENT FINDINGS: Recent studies have implicated contemporary ART regimens, including use of integrase strand transfer inhibitors and tenofovir alafenamide, as a contributor to weight gain, though the mechanisms are unclear. Metabolic dysregulation is linked to ectopic fat and alterations in adipose immune cell populations that accompany HIV and obesity. These factors contribute to an increasing burden of metabolic diseases in the aging HIV population. Obesity compounds an increasing burden of metabolic disease among PWH, and understanding the role of fat partitioning and HIV- and ART-related adipose tissue dysfunction may guide prevention and treatment strategies.


Assuntos
Tecido Adiposo/fisiopatologia , Antirretrovirais/efeitos adversos , Infecções por HIV/fisiopatologia , Obesidade/induzido quimicamente , Ganho de Peso/efeitos dos fármacos , Adipócitos/fisiologia , Adiposidade/efeitos dos fármacos , Antirretrovirais/uso terapêutico , Doenças Cardiovasculares/patologia , Diabetes Mellitus/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Inflamação/patologia , Hepatopatias/patologia , Doenças Metabólicas/patologia
8.
J Dermatol Sci ; 97(2): 152-160, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32001116

RESUMO

BACKGROUND: Radiation-induced skin injury is a serious concern during radiotherapy and radiation accidents. Skin fat represents the dominant architectural component of the human skin. However, the interplay between skin fat and the progression of radiation-induced skin injury remains largely unexplored. OBJECTIVE: This study aims to elucidate the interplay between skin fat and the progression of radiation-induced skin injury. METHODS: SD rats were irradiated with an electron beam. mRNA profiles were determined by RNA-Seq. The skin lipid mass was monitored by magnetic resonance imaging (MRI) and lipid profiles were measured by liquid chromatography-mass spectrometry (LC-MS). Human mature adipocytes isolated from dermal and subcutaneous white adipose tissues (WATs) were co-cultured with human keratinocytes (HaCaT) and skin fibroblasts (WS1) in the transwell culture system. Cell migration ability was measured by migration assay. RESULTS: Radiation modulated cutaneous lipid metabolism by downregulating multiple pathways. Moreover, radiation decreased skin fat mass with altered lipid metabolite profiles. The rats fed with a high-fat diet showed resistance to radiogenic skin injury compared with that with a control diet, indicating that skin lipid plays a radioprotective role. Mature adipocytes promoted the migration but not the proliferation of co-cultured skin keratinocytes and fibroblasts. Palmitic acid, the most abundant fatty acid in skin tissues, facilitated the migration of WS1 cells. Moreover, fatty acid-binding protein 4 (FABP4) could be incorporated into skin cells and promote DNA damage repair in irradiated skin fibroblasts. CONCLUSION: Radiation induces cutaneous lipid remolding, and skin adipocytes confer a protective role against radiation-induced skin injury.


Assuntos
Adipócitos/fisiologia , Resistência à Doença/fisiologia , Lesões por Radiação/patologia , Reepitelização/fisiologia , Dermatopatias/patologia , Adipócitos/efeitos da radiação , Animais , Movimento Celular , Técnicas de Cocultura , Dano ao DNA/efeitos da radiação , Reparo do DNA , Dieta Hiperlipídica , Modelos Animais de Doenças , Progressão da Doença , Proteínas de Ligação a Ácido Graxo/metabolismo , Fibroblastos , Humanos , Queratinócitos , Metabolismo dos Lipídeos/fisiologia , Metabolismo dos Lipídeos/efeitos da radiação , Ácido Palmítico/metabolismo , Cultura Primária de Células , RNA-Seq , Lesões por Radiação/etiologia , Ratos , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Dermatopatias/etiologia , Gordura Subcutânea/citologia , Gordura Subcutânea/efeitos da radiação
9.
PLoS One ; 15(2): e0229251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092101

RESUMO

Since chemerin's identification as an adipokine, it has been associated with a number of human diseases including diabetes and obesity. However, the basic scientific foundation for these clinical determinations is still lacking. Fibroblastic mouse 3T3 cells are unable to develop lipid droplets if chemerin is not present. Thus, we hypothesized that an in vivo rat model chemerin knockout (KO; an advancement from the previously mentioned in vitro cultures) would have limited accumulation of lipid in adipocytes compared to their wild-type (WT) counterparts. Female WT/KO rats (Sprague Dawley background) were fed a low-fat diet starting at 8 weeks of age with weekly body weight and food consumption monitoring. At 25 weeks of age, adipose tissue depots were dissected and flash frozen for PCR analysis or fixed with paraformaldehyde for histology. Over the 17 weeks of experimentation, WT and KO animals did not have differences in total body weight or food consumption but KO animals had a significantly reduced amount of visceral fat compared to WT animals (via microCT at 8 and 25 weeks). Histology of retroperitoneal and mesenteric depots demonstrated a significant leftward shift in adipocyte size in the mesenteric but not the retroperitoneal depot of the KO compared to WT animals. Similarly, in the mesenteric fat of the KO rat, gene expression of adiponectin, fatty acid synthase, perilipin, and leptin were significantly reduced compared to mesenteric fat of WT animals and retroperitoneal fat of both WT and KO animals. Adiponectin was highlighted by a protein-protein interaction network as being important for the physiological effects of chemerin removal. These data are the first, to our knowledge, to demonstrate chemerin's adipokine potential in vivo and identify it as fat depot location-specific.


Assuntos
Adipogenia/genética , Quimiocinas/análise , Adipócitos/fisiologia , Adipocinas/fisiologia , Tecido Adiposo/citologia , Animais , Peso Corporal , Quimiocinas/genética , Quimiocinas/fisiologia , Dieta com Restrição de Gorduras , Técnicas de Inativação de Genes , Gordura Intra-Abdominal , Gotículas Lipídicas , Mesentério/citologia , Ratos , Ratos Sprague-Dawley
10.
Nutrients ; 12(2)2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32041341

RESUMO

Deregulation of lipid metabolism and insulin function in muscle and adipose tissue are hallmarks of systemic insulin resistance, which can progress to type 2 diabetes. While previous studies suggested that milk proteins influence systemic glucose homeostasis and insulin function, it remains unclear whether bioactive peptides generated from whey alter lipid metabolism and its accumulation in muscle and adipose tissue. Therefore, we incubated murine 3T3-L1 preadipocytes and C2C12 myotubes with a whey peptide mixture produced through pepsin-pancreatin digestion, mimicking peptides generated in the gut from whey protein hydrolysis, and examined its effect on indicators of lipid metabolism and insulin sensitivity. Whey peptides, particularly those derived from bovine serum albumin (BSA), promoted 3T3-L1 adipocyte differentiation and triacylglycerol (TG) accumulation in accordance with peroxisome proliferator-activated receptor γ (PPARγ) upregulation. Whey/BSA peptides also increased lipolysis and mitochondrial fat oxidation in adipocytes, which was associated with the upregulation of peroxisome proliferator-activated receptor δ (PPARδ). In C2C12 myotubes, whey but not BSA peptides ameliorated palmitate-induced insulin resistance, which was associated with reduced inflammation and diacylglycerol accumulation, and increased sequestration of fatty acids in the TG pool. Taken together, our study suggests that whey peptides generated via pepsin-pancreatin digestion profoundly alter lipid metabolism and accumulation in adipocytes and skeletal myotubes.


Assuntos
Adipócitos/fisiologia , Diferenciação Celular/efeitos dos fármacos , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Proteínas do Soro do Leite/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Diglicerídeos/metabolismo , Inflamação , Camundongos , PPAR gama/metabolismo , Pancreatina/metabolismo , Pepsina A/metabolismo , Estimulação Química , Triglicerídeos/metabolismo
11.
Obes Facts ; 13(1): 86-101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31962332

RESUMO

OBJECTIVE: In obese individuals, chronic low-grade inflammation resulting from adipocyte-macrophage interactions is a major cause of adipose tissue dysfunction and metabolic disease. This study investigated the role of MAP kinase phosphatase-5 (MKP-5) in obesity-induced inflammation during macrophage and adipocyte interactions. METHODS: High-fat diet-induced obese mice were used to explore the role of MKP-5 in obesity-induced adipose tissue inflammation. Macrophage polarization was determined by inflammatory cytokine expression in MKP-5-overexpressed or -silenced Raw264.7 cells exposed to palmitate (PA) or M1/M2 macrophage inducers. To uncover the role of MKP-5 during macrophage-adipocyte interactions, a coculture system composed of differentiated 3T3-L1 and Raw264.7 cells was employed. MAPK inhibitors were used to investigate the involvement of MAPK signaling. RESULTS: Increased MKP-5 expression was observed in adipose stromal vascular cells (SVCs) of obese mice. In Raw264.7 cells, MKP-5 promoted the switching of M1 macrophages to an M2 phenotype. Notably, MKP-5 reduced inflammation during the interaction of macrophages and adipocytes. MKP-5 overexpression in primary SVCs attenuated the expression of inflammatory mediators and increased the number of obesity-induced adipose tissue macrophages. MKP-5 suppressed PA-induced inflammation through the inactivation of P38, JNK, and ERK MAPKs. CONCLUSIONS: MKP-5 promotes macrophages to switch from the M1 to the M2 phenotype and is an inflammatory inhibitor involved in obesity-induced adipose tissue inflammation and PA-triggered macrophage inflammation via the P38, JNK, and ERK MAPK pathways. MKP-5 may be developed into a potential therapeutic target for obesity-related diseases, including type 2 diabetes mellitus and insulin resistance.


Assuntos
Adipócitos/fisiologia , Comunicação Celular/genética , Fosfatases de Especificidade Dupla/fisiologia , Macrófagos/fisiologia , Obesidade/patologia , Células 3T3-L1 , Tecido Adiposo/patologia , Animais , Técnicas de Cocultura , Dieta Hiperlipídica , Fosfatases de Especificidade Dupla/genética , Células HEK293 , Humanos , Resistência à Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/genética , Células RAW 264.7
12.
Philos Trans R Soc Lond B Biol Sci ; 375(1793): 20190134, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-31928187

RESUMO

Endothermy changes the relationship between organisms and their environment fundamentally, and it is therefore of major ecological and evolutionary significance. Endothermy is characterized by non-shivering thermogenesis, that is metabolic heat production in the absence of muscular activity. In many eutherian mammals, brown adipose tissue (BAT) is an evolutionary innovation that facilitates non-shivering heat production in mitochondria by uncoupling food-derived substrate oxidation from chemical energy (ATP) production. Consequently, energy turnover is accelerated resulting in increased heat release. The defining characteristics of BAT are high contents of mitochondria and vascularization, and the presence of uncoupling protein 1. Recent insights, however, reveal that a range of stimuli such as exercise, diet and the immune system can cause the browning of white adipocytes, thereby increasing energy expenditure and heat production even in the absence of BAT. Here, we review the molecular mechanisms that cause browning of white adipose tissue, and their potential contribution to thermoregulation. The significance for palaeophysiology lies in the presence of adipose tissue and the mechanisms that cause its browning and uncoupling in all amniotes. Hence, adipocytes may have played a role in the evolution of endothermy beyond the more specific evolution of BAT in eutherians. This article is part of the theme issue 'Vertebrate palaeophysiology'.


Assuntos
Adipócitos/fisiologia , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/fisiologia , Evolução Biológica , Mamíferos/fisiologia , Termogênese , Animais , Aves/fisiologia
13.
J Cosmet Dermatol ; 19(3): 605-611, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31943721

RESUMO

BACKGROUND: Multiple studies have reported adipose tissue reduction after the application of the High-Intensity Focused Electromagnetic (HIFEM) field technology, yet cellular level evidence of the mechanisms has remained scarce. OBJECTIVES: This study aims to verify or refute previous single-study histological evidence and further investigates the proposed mechanism of apoptotic induction. METHODS: The thigh of two Large White pigs was treated with HIFEM for 30 minutes. Fat punch biopsies were collected from the application area before, immediately after, and 8 hours post-treatment. Control samples were taken from the abdomen immediately after and 8 hours post-treatment. Samples were analyzed for pro-apoptotic DNA markers (BAX, BCL-2, TXNIP, MMP9, TNF-α), the levels of free fatty acids (FFA), and the pH levels of the adipose tissue. RESULTS: The levels of FFA in the treated adipose tissue increased on average by 127.1% immediately post-treatment and by 134.1% 8 hours post-treatment, indicating a rapid breakdown of lipids. The average recorded adipose pH changed from 7.30 ± 0.12 at baseline to 6.60 ± 0.07 immediately post-treatment (P = .001) and to 7.19 ± 0.12 8 hours post-treatment. The levels of BAX, TXNIP, MMP9, and TNF-α increased post-treatment while BCL-2 decreased. Control samples showed constant levels of pH and pro-apoptotic markers. The FFAs in the control samples were increased by 41.6%-51.4%. CONCLUSION: The changes in the levels of the pro-apoptotic markers conformed to the previously reported elevated fat apoptosis post-HIFEM treatments. These effects were accompanied by an increase in FFA levels, and by reduced pH levels, due to the increased acidity in the adipose tissue. Further research is required to explore the potential of nonthermal induction of apoptosis.


Assuntos
Adipócitos/fisiologia , Apoptose/fisiologia , Contorno Corporal/métodos , Terapia de Campo Magnético/métodos , Gordura Subcutânea Abdominal/fisiologia , Animais , Ácidos Graxos não Esterificados/análise , Concentração de Íons de Hidrogênio , Modelos Animais , Gordura Subcutânea Abdominal/química , Gordura Subcutânea Abdominal/citologia , Sus scrofa
14.
Biochem Pharmacol ; 172: 113774, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31870769

RESUMO

Acetaminophen is both widely used to treat children with fever and is also responsible for thousands being hospitalised annually. Historically the antipyretic actions of acetaminophen were attributed to the inhibition of cyclooxygenase (COX-1/2) enzymes and more recently a novel COX-1 variant (COX-3) located in the brain. However, the evidence for acetaminophen-mediated COX inhibition remains contentious. This study assesses the impact of acetaminophen and other putative COX-3 inhibitors on the release of fatty acids during lipolysis as an alternative mechanism by which antipyretics can reduce body temperature during fever. 3T3-L1 adipocytes, primary brown adipocytes and isolated mitochondria were exposed to COX-3 inhibitors and lipolysis and mitochondrial electron transport chain function assessed. Acetaminophen, aminopyrine and antipyrine at 1-10 mM caused a significant decrease (up to 70%; P < 0.01, from control) in lipolysis within 1, 3 and 24 h without affecting cell viability. The inhibition was observed regardless of where along its signalling pathway lipolysis was stimulated. All three compounds were found to significantly attenuate mitochondrial function by up to 30% for complex I and 40% for complex II (P < 0.01, from control). These novel observations combined with the known limited inhibition of the COX enzymes by acetaminophen suggest both the antipyretic and hypothermia induced by acetaminophen and related compounds could be attributed to the direct inhibition of lipolysis and mitochondrial function, rather than cyclooxygenase inhibition centrally. Further these observations could provide new drug targets for reducing fever with the added bonus of fewer individuals being hospitalized by accidental acetaminophen overdose.


Assuntos
Acetaminofen/farmacologia , Adipócitos/efeitos dos fármacos , Antipiréticos/farmacologia , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Lipólise/efeitos dos fármacos , Células 3T3-L1 , 8-Bromo Monofosfato de Adenosina Cíclica/metabolismo , Adipócitos/fisiologia , Agonistas Adrenérgicos beta/farmacologia , Aminopirina/farmacologia , Animais , Antipirina/farmacologia , Diferenciação Celular , Colforsina/metabolismo , Isoproterenol/farmacologia , Camundongos , Ratos , Ratos Wistar
15.
Exp Cell Res ; 387(2): 111753, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837293

RESUMO

PURPOSE: The metabolic syndrome (MetS) is characterized of a cluster of medical disorders. Altered function of adipose tissue has a significant impact on whole-body metabolism and represents a key driver for MetS. In this study, we aim to explore the function of human circular RNA H19 (hsa_circH19) in human adipose-derived stem cells (hADSCs). METHODS: The blood samples from MetS patients and normal subjects were used to determine the expression level of the hsa_circH19. After knock-down of hsa_circH19 in hADSCs, we measured the expression of adipogenic genes. Oil red O, Nile red staining assay and triglyceride assessment were performed to examine the role of hsa_circH19 in hADSCs differentiation. Then, RNA Pull-down and RIP assays were conducted to explore the related RNA binding protein of hsa_circH19. IF was performed to determine the potential molecular regulatory mechanism. RESULTS: After accounting for confounding factors, high levels of hsa_circH19 remained an independent risk factor for MetS. Furthermore, the knockdown of hsa_circH19 significantly increased the expression of adipogenic genes and the formation of lipid droplets. Bioinformatics analyses revealed that has_circH19 shared multiple binding sites with polypyrimidine tract-binding protein 1 (PTBP1) and their interaction was validated by circRNA pull-down and RIP assays. Mechanistically, depletion of hsa_circH19 triggered translocation of sterol-regulatory element binding proteins (SREBP1) from cytoplasm to nucleus in the presence of PTBP1. CONCLUSION: Our experiments suggest that knockdown of hsa_circH19 promotes hADCSs adipogenic differentiation via targeting of PTBP1. In consequence, the expression of hsa_circH19 might correlated to lipid metabolism in adipose tissue from MetS.


Assuntos
Adipogenia/genética , Adipogenia/fisiologia , Tecido Adiposo/fisiologia , Diferenciação Celular/genética , RNA Circular/genética , RNA Longo não Codificante/genética , Adipócitos/fisiologia , Idoso , Feminino , Ribonucleoproteínas Nucleares Heterogêneas , Humanos , Masculino , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
16.
J Invest Dermatol ; 140(1): 75-84.e6, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31351086

RESUMO

Rac signaling affects numerous downstream targets in vitro; however, few studies have established in vivo levels. We generated mice with a single knockout (KO) of Rac1 (Keratin5(K5)-Cre;Rac1flox/flox, Rac1-KO) and double KO of Rac1 and Rac3 (K5-Cre;Rac1flox/flox;Rac3-/-, Rac1/Rac3-DKO) in keratinocytes. The hairless phenotype in Rac1-KO mice was markedly exacerbated in Rac1/Rac3-DKO mice. Strikingly, Rac1-KO mice exhibited thinner dermal white adipose tissue, which was considerably further reduced in Rac1/Rac3-DKO mice. DNA microarray using primary keratinocytes from Rac1/Rac3-DKO mice exhibited decreased mRNA levels of Bmp2, Bmp5, Fgf20, Fgf21, Fgfbp1, and Pdgfα. Combinational treatment with bone morphogenetic protein (BMP) 2 and fibroblast growth factor (FGF) 21 in culture medium, but not individual purified recombinant proteins, could differentiate 3T3-L1 fibroblasts into adipocytes, as could culture media from primary keratinocytes. Conversely, addition of anti-BMP2 or anti-FGF21 antibodies into the culture medium inhibited fibroblast differentiation. In addition, BMP2 and FGF21 treatment promoted adipocyte differentiation only of rat primary white adipocyte precursors but not rat primary brown adipocyte precursors. Furthermore, BMP2 and FGF21 treatment enhanced adipogenesis of normal human dermal fibroblasts. Notably, brown adipogenesis promoted by FGF21 was inhibited by BMP2. Thus, we propose a complex paracrine pathway from keratinocytes to intradermal pre-adipocytes, which functions as a Rac-dependent modulator of both white and brown adipogenesis.


Assuntos
Adipócitos/fisiologia , Tecido Adiposo Branco/fisiologia , Derme/patologia , Queratina-5/genética , Queratinócitos/fisiologia , Proteínas rac de Ligação ao GTP/genética , Animais , Proteína Morfogenética Óssea 2/genética , Diferenciação Celular , Regulação para Baixo , Fatores de Crescimento de Fibroblastos/genética , Camundongos , Camundongos Knockout , Células NIH 3T3 , Comunicação Parácrina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Análise Serial de Tecidos
17.
Anim Biotechnol ; 31(1): 17-24, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30570352

RESUMO

GTP binding protein overexpressed in skeletal muscle (GEM) is an important gene with many functions, such as regulating the rearrangement of cytoskeleton and the activity of voltage-dependent calcium channel, and GEM was regarded as a candidate gene for obesity. However, little investigation has been carried out to explore whether GEM affected the intramuscular fat (IMF) deposition of goat. To explore the role of GEM gene in goat, this gene was cloned and its tissue and temporal expression profile were detected. Effect of GEM on adipogenesis was examined by losing function of GEM in vitro. Thereafter, several lipid metabolism-related genes were examined, including CCAAT/enhancing-binding protein α (C/EBPα), CCAAT/enhancing-binding protein ß (C/EBPß), lipoprotein lipase (LPL), preadipocyte factor 1 (Pref-1), peroxisome proliferator activated receptor γ (PPARγ) and sterol regulatory element binding protein 1 (SREBP1). We found that the goat GEM gene consisted of 936 bp, which encoded a protein of 311 amino acids. The expression of GEM was higher in spleen, lung and large intestine and it appeared sharp in the interim stage of differentiation. Furthermore, GEM knockdown blocked adipogenesis and the expression of C/EBPα, C/EBPß, LPL, PPARγ and SREBP1. These results indicated that GEM might promote lipid accumulation and adipogenesis.


Assuntos
Adipogenia/genética , Proteínas de Ligação ao GTP/genética , Cabras/genética , Metabolismo dos Lipídeos/genética , Adipócitos/fisiologia , Sequência de Aminoácidos , Animais , Diferenciação Celular , Técnicas de Silenciamento de Genes/veterinária , Cabras/fisiologia , Intestino Grosso/fisiologia , Pulmão/fisiologia , Masculino , Músculo Esquelético/fisiologia , Alinhamento de Sequência/veterinária , Baço/fisiologia
18.
Cell Mol Life Sci ; 77(12): 2407-2421, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31515577

RESUMO

Epigenetic modifications play a central role in cell differentiation and development. In the current study, we have recognized lysine demethylase 4A (KDM4A) as a novel epigenetic regulator of osteoblast and adipocyte differentiation. Kdm4a expression was upregulated during osteogenesis and adipogenesis of primary marrow stromal cells and established stromal ST2 line. Overexpression of wild-type Kdm4a promoted adipogenic differentiation and blocked osteogenic differentiation of the progenitor cells. This effect was largely alleviated when the catalytically dead mutation was made. Conversely, depletion or inactivation of Kdm4a in undifferentiated progenitor cells inhibited the formation of adipocytes and promoted the differentiation of osteoblasts. Mechanism explorations showed that overexpression of Kdm4a upregulated the expression of secreted frizzled-related protein 4 (Sfrp4) and CCAAT/enhancer-binding protein α (C/ebpα). Chromatin immunoprecipitation assay demonstrated that KDM4A directly bound the promoters of Sfrp4 and C/ebpα, removed the histone methylation mark H3K9me3, and reduced DNA methylation levels of CpG in promoter regions of C/ebpα and Sfrp4. Furthermore, overexpression of Kdm4a inactivated canonical Wnt signaling. Moreover, activation of canonical Wnt signaling through silencing of Sfrp4 in ST2 attenuated the inhibition of osteogenic differentiation and the enhancement of adipogenic differentiation by KDM4A. These data have identified KDM4A as a novel regulator of osteoblast and adipocyte differentiation and suggest KDM4A inhibition as a potential therapeutic target for treating metabolic disorders such as osteoporosis.


Assuntos
Adipogenia/genética , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Diferenciação Celular/genética , Epigênese Genética/genética , Histona Desmetilases/genética , Osteogênese/genética , Via de Sinalização Wnt/genética , Adipócitos/fisiologia , Animais , Diferenciação Celular/fisiologia , Histonas/genética , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/fisiologia , Regiões Promotoras Genéticas/genética , Células-Tronco/fisiologia , Células Estromais/fisiologia , Ativação Transcricional/genética , beta Catenina/genética
19.
Curr Stem Cell Res Ther ; 15(1): 77-85, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31483236

RESUMO

Burns are a global public health issue of great concern. The formation of scars after burns and physical dysfunction of patients remain major challenges in the treatment of scars. Regenerative medicine based on cell therapy has become a hot topic in this century. Adipose-derived stem cells (ADSCs) play an important role in cellular therapy and have become a promising source of regenerative medicine and wound repair transplantation. However, the anti-scarring mechanism of ADSCs is still unclear yet. With the widespread application of ADSCs in medical, we firmly believe that it will bring great benefits to patients with hypertrophic scars.


Assuntos
Adipócitos/fisiologia , Cicatriz Hipertrófica/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Animais , Diferenciação Celular , Regeneração Tecidual Guiada , Humanos , Tecidos Suporte , Cicatrização
20.
J Plast Reconstr Aesthet Surg ; 73(1): 176-183, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31451405

RESUMO

INTRODUCTION: Face transplantation can offer patients with severe facial deformities a better quality of life, but questions of donor suitability remain unanswered. The aim of this study is to determine how an obesity mismatch between donor and recipient affects facial fat graft retention and cellular properties, potentially increasing the donor pool substantially. We hypothesized that facial fat would respond to the microenvironment of the recipient and developed an animal model to evaluate this hypothesis. METHODS: This study utilized 30 C57BL/6J wild-type (WT) and 30 diet-induced obese (DIO), immunologically identical mice. One hundred seventy-five micrograms of perigonadal fat was harvested from 10 mice from each group and transplanted to the subcutaneous scalp of the remaining mice. Ten DIO mice were implanted with DIO donor fat and 10 with WT donor fat. The 10 WT mice were implanted with DIO fat and 10 with WT fat. Recipients underwent micro-CT scans at 2 days and 2, 4, 6, 8, 10, and 12 weeks postoperation. Scans were 3D-reconstructed to assess transplanted fat volume. At 12 weeks, the transplanted fat was analyzed by hematoxylin-eosin staining. RESULTS: Volume retention of the transplanted fat depended on recipient phenotype, which was confirmed through ANOVA and Student-Newman-Keuls test. Graft volume with a DIO recipient increased with both a DIO (25.6%) and a WT (24.4%) donor from 2 days to 12 weeks postoperation. In a WT recipient, graft volume decreased when the donor was WT (54.0%) and DIO (53.0%). Average cellular volume was also dependent on the recipient phenotype. CONCLUSION: This study demonstrates that fat transplanted to the facial region responds to the surrounding microenvironment both macroscopically and microscopically. This study has large implications in donor suitability in face transplant, as it indicates that a donor-recipient obesity mismatch may be acceptable.


Assuntos
Tecido Adiposo/transplante , Transplante de Face , Sobrevivência de Enxerto/fisiologia , Adaptação Fisiológica/fisiologia , Adipócitos/fisiologia , Tecido Adiposo/citologia , Tecido Adiposo/fisiologia , Aloenxertos/fisiologia , Análise de Variância , Animais , Tamanho Celular , Modelos Animais de Doenças , Imageamento Tridimensional , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Transplante Homólogo , Ganho de Peso/fisiologia , Microtomografia por Raio-X
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