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1.
Exp Suppl ; 111: 419-441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588542

RESUMO

Obesity is caused by an imbalance between energy intake and output, influenced by numerous environmental, biological, and genetic factors. Only a minority of people with obesity have a genetic defect that is the main cause of their obesity. A key symptom for most of these disorders is early-onset obesity and hyperphagia. For some genetic obesity disorders, the hyperphagia is the main characteristic, often caused by disruptions of the leptin-melanocortin pathway, the central pathway that regulates the body's satiety and energy balance. For other disorders, obesity is part of a distinct combination of other clinical features such as intellectual disability, dysmorphic facial features, or organ abnormalities. This chapter focuses on genetic obesity disorders and also summarizes the present knowledge on the genetics of the more common polygenic/multifactorial obesity.


Assuntos
Hiperfagia/genética , Obesidade/genética , Ingestão de Energia , Metabolismo Energético , Humanos , Leptina , Melanocortinas , Saciação
2.
J Agric Food Chem ; 67(38): 10595-10603, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31475817

RESUMO

While ß-cryptoxanthin is hypothesized to have a preventive effect on lifestyle-related diseases, its underlying mechanisms are unknown. We investigated the effect of ß-cryptoxanthin on energy metabolism in adipose tissues and its underlying mechanism. C57BL/6J mice were fed a high-fat diet (60% kcal fat) containing 0 or 0.05% ß-cryptoxanthin for 12 weeks. ß-cryptoxanthin treatment was found to reduce body fat gain and plasma glucose level, while increasing energy expenditure. The expression of uncoupling protein (UCP) 1 was elevated in adipose tissues in the treatment group. Furthermore, the in vivo assays showed that the Ucp1 mRNA expression was higher in the ß-cryptoxanthin treatment group, an effect that disappeared upon cotreatment with a retinoic acid receptor (RAR) antagonist. In conclusion, we report that ß-cryptoxanthin reduces body fat and body weight gain and that ß-cryptoxanthin increases the expression of UCP1 via the RAR pathway.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , beta-Criptoxantina/administração & dosagem , Obesidade/tratamento farmacológico , Receptores do Ácido Retinoico/metabolismo , Proteína Desacopladora 1/genética , Animais , Metabolismo Energético/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Receptores do Ácido Retinoico/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo
3.
J Agric Food Chem ; 67(37): 10352-10360, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31503479

RESUMO

The potential for apple peels to mitigate the deleterious effects of a high-fat diet in mice was investigated here. Mice were fed a high-fat diet supplemented with apple powders from three apple varieties or a commercial apple polyphenol. Polyphenols were characterized using colorimetric assays and high-performance liquid chromatography. Mice were tested for standard metabolic parameters. There was a dose response to dietary apple peels, with the higher intake leading to reduced weight gain and adipose tissue mass relative to the lower intake, but none of the treatments were statistically different from the control. The gene expression of liver enzyme stearoyl-CoA desaturase (Scd-1) was correlated with adipose weight, and liver enzyme cytochrome P51 (Cyp51) was downregulated by the apple diets. The feces from a subset of mice were analyzed for polyphenols and for bacteria taxa by next-generation sequencing. The results revealed that the makeup of the fecal microbiota was related to the metabolism of dietary polyphenols.


Assuntos
Biflavonoides/análise , Catequina/análise , Fezes/química , Frutas/metabolismo , Microbioma Gastrointestinal , Malus/metabolismo , Obesidade/dietoterapia , Proantocianidinas/análise , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biflavonoides/metabolismo , Catequina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Frutas/química , Humanos , Masculino , Malus/química , Camundongos , Obesidade/genética , Obesidade/metabolismo , Obesidade/microbiologia , Polifenóis/análise , Polifenóis/metabolismo , Proantocianidinas/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Esterol 14-Desmetilase/genética , Esterol 14-Desmetilase/metabolismo
4.
Arch Endocrinol Metab ; 63(4): 402-410, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365628

RESUMO

OBJECTIVE: The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. SUBJECTS AND METHODS: The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. RESULTS: The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). CONCLUSIONS: We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.


Assuntos
Obesidade/genética , Sobrepeso/genética , Polimorfismo Genético/genética , Sistema Renina-Angiotensina/genética , Adulto , Distribuição por Idade , Angiotensinogênio/genética , Pressão Sanguínea , Índice de Massa Corporal , Brasil , Estudos Transversais , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , Distribuição por Sexo , Circunferência da Cintura
5.
Adv Exp Med Biol ; 1193: 135-154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368102

RESUMO

Obesity is multifactorial and complex. Remarkable progress has been made recently in search for polygenic obesity through genome-wide association study (GWAS), but biology of polygenic effects on obesity is largely poor. This review summarizes the available evidence and provides an overview of the links between ALDH2 variants and adiposity, which were firstly and mainly derived from studies of polygenic obesity and also indirectly investigated by using cell lines and mice. The genetic association studies have observed consistent associations of ALDH2 variants with obesity-related traits including BMI, waist circumference (WC), waist-to-hip ratio (WHR), and visceral fat accumulation. In consideration of ALDH2 variants with enzyme activity and alcohol consumption behavior in physiological mechanism studies, we proposed a model by which the physiological and behavioral consequences of alcohol consumption serve as an intermediary process between polymorphisms in ALDH2 and obesity.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Obesidade/genética , Adiposidade/genética , Animais , Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Polimorfismo de Nucleotídeo Único , Circunferência da Cintura , Relação Cintura-Quadril
6.
Anticancer Res ; 39(8): 4475-4478, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366547

RESUMO

Chronic inflammation is involved in the development of cancer, lifestyle-related diseases, and autoimmune diseases. It also influences the severity of these diseases. Macrophages that accumulate in tumor tissues and adipose tissues of obesity have been shown to increase expression of inflammatory cytokines, thereby inducing inflammatory changes in these tissues. The macrophage phenotype is believed to be important in mediating inflammatory changes in tissues. Recently, monocytes/macrophages activated with low-dose lipopolysaccharide (LPS) were demonstrated to suppress increased expression of monocyte chemotactic protein (MCP)-1 and inflammatory cytokines (interleukin (IL)-1 ß, IL-8, and tumor necrosis factor (TNF)-α). By suppressing the increased expression of chemotaxis-related and inflammation-related factors, monocytes/macrophages activated with low-dose LPS are considered to suppress the migration of macrophages into tissues and to regulate inflammatory changes in these tissues, respectively. The effects of macrophages activated with low-dose LPS were different from those of macrophages activated with high-dose LPS. In this review, we discuss the usefulness of monocytes/macrophages activation by low-dose LPS.


Assuntos
Inflamação/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Neoplasias/tratamento farmacológico , Obesidade/genética , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Quimiocina CCL2/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Interleucina-1beta/genética , Interleucina-8/genética , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Neoplasias/genética , Obesidade/patologia , Fator de Necrose Tumoral alfa/genética
7.
J Agric Food Chem ; 67(36): 10107-10115, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31434473

RESUMO

We examined the antiobesity effect of a limonoid 7-deacetoxy-7-oxogedunin, named CG-1, purified from the seeds of Carapa guianensis, Meliaceae, known as andiroba in high-fat-diet (HFD)-fed mice. C57BL/6 mice were fed a low-fat diet or an HFD and orally administered CG-1 (20 mg/kg) for 7 weeks. CG-1 lowered the body weight gain and improved the serum triglyceride level and insulin sensitivity in HFD-fed mice. The expression level of the adipogenesis-related genes was lowered by CG-1 in the visceral white adipose tissue (vWAT). The mRNA expression level of the macrophage-related genes decreased in vWAT following the administration of CG-1 to HFD-fed mice. It is noteworthy that CG-1 activated the brown adipose tissue (BAT) with enhanced expression of uncoupling protein 1 and increased the rectal temperature in HFD-fed mice. These results indicate that the limonoid CG-1 decreased body weight gain and ameliorated hypertriglyceridemia and insulin resistance with the activation of BAT in HFD-fed mice.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/administração & dosagem , Resistência à Insulina , Limoninas/administração & dosagem , Meliaceae/química , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Sementes/química , Triglicerídeos/sangue , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Ganho de Peso/efeitos dos fármacos
8.
BMJ ; 366: l4067, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270083

RESUMO

OBJECTIVES: To study the trajectories of body mass index (BMI) in Norway over five decades and to assess the differential influence of the obesogenic environment on BMI according to genetic predisposition. DESIGN: Longitudinal study. SETTING: General population of Nord-Trøndelag County, Norway. PARTICIPANTS: 118 959 people aged 13-80 years who participated in a longitudinal population based health study (Nord-Trøndelag Health Study, HUNT), of whom 67 305 were included in analyses of association between genetic predisposition and BMI. MAIN OUTCOME MEASURE: BMI. RESULTS: Obesity increased in Norway starting between the mid-1980s and mid-1990s and, compared with older birth cohorts, those born after 1970 had a substantially higher BMI already in young adulthood. BMI differed substantially between the highest and lowest fifths of genetic susceptibility for all ages at each decade, and the difference increased gradually from the 1960s to the 2000s. For 35 year old men, the most genetically predisposed had 1.20 kg/m2 (95% confidence interval 1.03 to 1.37 kg/m2) higher BMI than those who were least genetically predisposed in the 1960s compared with 2.09 kg/m2 (1.90 to 2.27 kg/m2) in the 2000s. For women of the same age, the corresponding differences in BMI were 1.77 kg/m2 (1.56 to 1.97 kg/m2) and 2.58 kg/m2 (2.36 to 2.80 kg/m2). CONCLUSIONS: This study provides evidence that genetically predisposed people are at greater risk for higher BMI and that genetic predisposition interacts with the obesogenic environment resulting in higher BMI, as observed between the mid-1980s and mid-2000s. Regardless, BMI has increased for both genetically predisposed and non-predisposed people, implying that the environment remains the main contributor.


Assuntos
Índice de Massa Corporal , Predisposição Genética para Doença , Obesidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Obesidade/epidemiologia , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto Jovem
10.
DNA Cell Biol ; 38(8): 754-762, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31305133

RESUMO

Polycystic ovary syndrome (PCOS) is the most typical metabolic syndrome in women of reproductive age, with a high prevalence and an increased risk of long-term complications. PCOS mainly manifests as hyperandrogenism (HA), ovulatory dysfunction, and polycystic ovaries, in addition to being relevant to infertility, insulin resistance (IR), obesity, lipid abnormalities, and chronic low-grade inflammation. The etiology of this syndrome remains largely unknown. microRNAs (miRNAs), small, noncoding RNAs (nearly 22 nucleotides long), regulate gene expression at the posttranscriptional level. Abnormal miRNA levels are closely associated with the occurrence of diseases, such as diabetes, cancers, and atherosclerosis, and miRNAs can be used as predictors and diagnostic biomarkers for cancer. Interestingly, the roles of miRNAs in PCOS pathology have attracted considerable attention in recent years. Research has established that alterations in miRNA expression in women with PCOS compared with healthy women may act as noninvasive biomarkers and new therapeutic targets in PCOS. This article aims to summarize the latest research on the relationship between miRNAs and the clinical manifestations of PCOS while also providing a few mechanisms based on previous studies. Understanding the relationship between miRNAs and PCOS will provide guidance for researchers to further explore the complexity and heterogeneity of PCOS.


Assuntos
Androgênios/metabolismo , Biomarcadores/sangue , MicroRNAs , Síndrome do Ovário Policístico/genética , Androgênios/genética , Dislipidemias/genética , Feminino , Regulação da Expressão Gênica , Humanos , Resistência à Insulina/genética , MicroRNAs/sangue , Obesidade/genética , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/patologia , Ovário/fisiologia , Síndrome do Ovário Policístico/etiologia
11.
Cell Mol Life Sci ; 76(20): 4009-4021, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31270580

RESUMO

Imprinted genes display parent-of-origin-specific expression with this epigenetic system of regulation found exclusively in therian mammals. Historically, defined imprinted gene functions were almost solely focused on pregnancy and the influence on the growth parameters of the developing embryo and placenta. More recently, a number of postnatal functions have been identified which converge on resource allocation, both for animals in the nest and in adults. While many of the prenatal functions of imprinted genes that have so far been described adhere to the "parental conflict" hypothesis, no clear picture has yet emerged on the functional role of imprints on postnatal metabolism. As these roles are uncovered, interest in the potential for these genes to influence postnatal metabolism and associated adult-onset disease outcomes when dysregulated has gathered pace. Here, we review the published data on imprinted genes and their influence on postnatal metabolism, starting in the nest, and then progressing through to adulthood. When observing the functional effects of these genes on adult metabolism, we must always be careful to acknowledge the influence both of direct expression in the relevant metabolic tissue, but also indirect metabolic programming effects caused by their modulation of both in utero and postnatal growth trajectories.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação da Expressão Gênica no Desenvolvimento , Impressão Genômica , Herança Materna , Herança Paterna , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Animais , Comportamento Animal , Regulação da Temperatura Corporal/genética , Embrião de Mamíferos , Desenvolvimento Embrionário , Feminino , Humanos , Masculino , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Placenta/metabolismo , Gravidez
13.
Nat Commun ; 10(1): 2581, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197173

RESUMO

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.


Assuntos
Metilação de DNA/fisiologia , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Insulina/metabolismo , Obesidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Ilhas de CpG/genética , Diabetes Mellitus Tipo 2/metabolismo , Epigênese Genética/fisiologia , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Estudo de Associação Genômica Ampla/métodos , Homeostase/genética , Humanos , Masculino , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Obesidade/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto Jovem
14.
Gene ; 711: 143938, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31220580

RESUMO

BACKGROUND AND PURPOSE: The pathogenesis of endometrial cancer (EC) involves many regulatory pathways including transcriptional regulatory networks supported by transcription factors and microRNAs only in part known. The aim of this retrospective study was to explore the possible correlation in the EC microenvironment between master regulators of complex phenomena such as steroid responsiveness through estrogen receptor alpha (ERα) and progesterone receptor (PR), epithelial-to-mesenchymal transition (supported by SLUG transcription factor), hypoxia (with hypoxia inducible factor-1 alpha, HIF-1α), and obesity that has been recognized as a EC risk factor. METHODS: Formalin-Fixed Paraffin-Embedded (FFPE) blocks from University of Ferrara Pathology Archive were used and allocated into 2 groups according to their immunohistochemical positivity to ERα and PR, distinguishing the samples with a more benign prognosis (ERα+/PR+) from those with a poorer prognosis (ERα-/PR-). Immunohistochemistry for HIF1-α and SLUG was also performed. Body mass index (BMI) was registered at the time of diagnosis: patients with BMI ≥ 30 kg/m2 were defined obese (OB). Total RNA was isolated for miR-221 analysis. RESULTS: We showed a comparable percentage of HIF1-α and SLUG positive samples in the ERα+/PR+ and ERα-/PR- groups. However, the obesity factor impacted more in the ERα+/PR+ group since the ratio between OB and non-obese (NOB) patients with high expression of HIF1-α and SLUG was higher in ERα+/PR+ than in the ERα-/PR- group. miR-221 levels were significantly higher in the OB than NOB patients, and, also in this case, obesity impacted more in the ERα+/PR+ group. CONCLUSIONS: A molecular circuit of mutual regulation between ERα, PR, HIF1-α, SLUG and miR-221 is feasible in the EC and was firstly suggested by our research. In this interplay miR-221 seems to be in a nodal point of the regulatory system that is particularly strengthened by the metabolic changes in obesity.


Assuntos
Neoplasias do Endométrio/genética , Receptor alfa de Estrogênio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , MicroRNAs/genética , Obesidade/genética , Receptores de Progesterona/metabolismo , Fatores de Transcrição da Família Snail/genética , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pessoa de Meia-Idade , Obesidade/metabolismo , Estudos Retrospectivos , Fatores de Risco , Fatores de Transcrição da Família Snail/metabolismo , Microambiente Tumoral
15.
Nat Commun ; 10(1): 2375, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147543

RESUMO

Human antigen R (HuR) is a member of the Hu family of RNA-binding proteins and is involved in many physiological processes. Obesity, as a worldwide healthcare problem, has attracted more and more attention. To investigate the role of adipose HuR, we generate adipose-specific HuR knockout (HuRAKO) mice. As compared with control mice, HuRAKO mice show obesity when induced with a high-fat diet, along with insulin resistance, glucose intolerance, hypercholesterolemia and increased inflammation in adipose tissue. The obesity of HuRAKO mice is attributed to adipocyte hypertrophy in white adipose tissue due to decreased expression of adipose triglyceride lipase (ATGL). HuR positively regulates ATGL expression by promoting the mRNA stability and translation of ATGL. Consistently, the expression of HuR in adipose tissue is reduced in obese humans. This study suggests that adipose HuR may be a critical regulator of ATGL expression and lipolysis and thereby controls obesity and metabolic syndrome.


Assuntos
Tecido Adiposo Branco/metabolismo , Proteína Semelhante a ELAV 1/genética , Intolerância à Glucose/genética , Hipercolesterolemia/genética , Resistência à Insulina/genética , Lipase/genética , Obesidade/genética , Adipócitos/patologia , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/imunologia , Animais , Crescimento Celular , Dieta Hiperlipídica , Proteína Semelhante a ELAV 1/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Intolerância à Glucose/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Hipertrofia , Inflamação/imunologia , Lipase/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Biossíntese de Proteínas , Estabilidade de RNA/genética , Gordura Subcutânea/metabolismo
16.
Lipids Health Dis ; 18(1): 111, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077211

RESUMO

BACKGROUND: Hepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses. METHODS: A total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies. RESULTS: SNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01). CONCLUSION: Our data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.


Assuntos
Desoxiguanosina/análogos & derivados , Estudos de Associação Genética , Pleiotropia Genética , Lipase/genética , Lipídeos/sangue , Polimorfismo de Nucleotídeo Único/genética , Biomarcadores/sangue , HDL-Colesterol/sangue , Desoxiguanosina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Obesidade/sangue , Obesidade/genética , Caracteres Sexuais , Triglicerídeos/sangue
17.
Phytother Res ; 33(7): 1851-1864, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31119811

RESUMO

We investigated the effects of the prenylated flavonoid-standardized extract (PFE) from the seeds of Psoralea corylifolia L. on countering obesity, which increases energy expenditure and stimulates thermogenesis in subcutaneous white adipose tissue (sWAT) and brown adipose tissue (BAT). For 12 weeks, C57BL/6 mice were fed a controlled high-fat diet (HFD) or HFDs with 0.2% or 0.5% w/w PFE. In vitro, the differentiation of 3 T3-L1 cells was used to elicit thermogenesis in the presence of PFE. PFE obviously reduced body weight and fat mass in a dose-dependent manner, increased energy expenditure, improved insulin sensitivity, and prevented hepatic steatosis by increasing lipid oxidation and secretion in HFD-fed mice. Moreover, PFE induced clear browning in sWAT, significantly increased phosphorylation of AMPKα1/2 and p38, increased BAT activity and the differentiation of 3 T3-L1 by increasing the expression of uncoupling protein 1 and other thermogenic genes. Our study showed that PFE prevented obesity by increasing browning and activating thermogenic genes in sWAT and BAT, improving glucose homeostasis, and protecting hepatic steatosis.


Assuntos
Fármacos Antiobesidade/farmacologia , Flavonoides/farmacologia , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Psoralea , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Prenilação , Sementes , Termogênese/efeitos dos fármacos
18.
Int J Mol Sci ; 20(8)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991630

RESUMO

Studies indicate the heritable nature of affective temperament, which shows personality traits predisposing to the development of mental disorders. Dopaminergic gene polymorphisms such as DRD4, COMTVal158Met, and DAT1 have been linked to affective disorders in obesity. Due to possible correlation between the aforementioned polymorphisms and the affective temperament, the aim of our research was to investigate this connection in an obese population. The study enrolled 245 obese patients (178 females; 67 males). The affective temperament was assessed using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego autoquestionnaire (TEMPS-A). Genetic polymorphisms of DAT1, COMTVal158Met and DRD4 were collected from peripheral blood sample and determined using a polymerase chain reaction (PCR). Only in COMT polymorphisms, the cyclothymic and irritable dimensions were significantly associated with Met/Val carriers (p = 0.04; p = 0.01). Another interesting finding was the correlation between the affective temperament and age in men and women. We assume that dopamine transmission in heterozygotes of COMT may determine the role of the affective temperament in obese persons. Dopaminergic transmission modulated by COMT may be responsible for a greater temperament expression in obese individuals. To our knowledge, this is the first study describing the role of affective temperament in the obese population, but more research is needed in this regard.


Assuntos
Catecol O-Metiltransferase/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Transtornos do Humor/genética , Obesidade/genética , Polimorfismo Genético , Receptores de Dopamina D4/genética , Adulto , Dopamina/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Obesidade/complicações , Temperamento
19.
Lipids Health Dis ; 18(1): 97, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975133

RESUMO

BACKGROUND: Evidence shows that low serum vitamin D concentrations account for an increased risk of obesity by inducing vitamin D receptor (VDR) hypofunction. Although the correlation between single nucleotide polymorphisms (SNPs) of VDR gene and obesity-related anthropometric measures (such as body mass index [BMI] and waist circumference[WC]) has already been tested, there are only few studies on the association between direct measures of body fat percentage (BFP) and triceps skinfold thickness and the SNPs of VDR. The aim of the present study was to evaluate the effect of VDR gene polymorphism on multiple obesity indexes in Han Chinese, including BMI, WC, BFP and triceps skinfold thickness. METHODS: In this cross-sectional study, five hundred and seventeen healthy Chinese adults were enrolled in the trial. Four loci in VDR gene (rs2228570 [FokI], rs2189480, rs2239179 and rs7975232[ApaI]) were genotyped by TaqMan probe assays. Obesity indexes including BMI, WC, BFP and triceps skinfold thickness were used to evaluate the relationship to the VDR SNPs. Multiple logistic regression, linear regression and general multifactor dimensionality reduction (GMDR) were performed to analyze the correlation of VDR gene and obesity indexes. RESULTS: None of the VDR SNPs were associated with BMI and WC, the C allele of FokI and the T allele of ApaI were associated with an increase in BFP (ß = 0.069,P = 0.007; ß = 0.087, P = 0.022 respectively); the G allele of rs2239179 and the T allele of ApaI were associated with an increase in triceps skin fold thickness (ß = 0.074, P = 0.001; ß = 0.122, P < 0.001 respectively). In regards to adiposity-related metabolic parameters, we found that the GT genotype of ApaI was associated with higher level of total cholesterol (TC) (P = 0.013) and Low-density lipoprotein cholesterol (LDL-C) (P = 0.001). CONCLUSIONS: Though we failed to prove that VDR SNPs were in correlation with BMI and WC, we did establish the association between VDR variants and BFP, as well as triceps skinfold thickness. Data obtained suggested that the VDR variants play an important role in regulating adipose tissue activity and adiposity among Han Chinese.


Assuntos
Tecido Adiposo/metabolismo , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Pregas Cutâneas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Índice de Massa Corporal , China/epidemiologia , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Expressão Gênica , Loci Gênicos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redução Dimensional com Múltiplos Fatores , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/epidemiologia , Receptores de Calcitriol/sangue , Circunferência da Cintura
20.
J Biol Regul Homeost Agents ; 33(2): 517-523, 2019 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30972993

RESUMO

This study aimed to investigate the effect of different exercise loads on sex hormones and expressions of relevant genes in hypothalamus in obese mice. Sixty weaning male C57BL/6 mice were used as subjects. Among them, 15 mice were randomly classified into the normal diet group (CON group), and the remaining 45 mice into high-fat diet group (MOB group). The obesity was successfully achieved by high-fat diet 10 weeks later. Then the rats were randomly divided into three groups based on weight, namely, obesity control group (OBC group), obesity with moderate-intensity exercise group (MOBC group), and obesity with high-intensity exercise group (HOBC group), with 15 mice in each group. Mice in the MOBC group and HOBC group were offered 8 weeks of swimming training, and the exercise time increased incrementally until 2 h and 4 h per day. After the training was over, ELISA method was used to determine the serum levels of Adiponectin (Adipo), luteotropic hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T). Real-time PCR was implemented to detect the transcriptional levels of genes of Adipo and other relevant proteins in the hypothalamus. The result showed that compared with the CON group, there was a significant reduction in the serum levels of Adipo, LH, FSH and T in the OBC group (P<0.05). As compared with the OBC group, the serum levels of Adipo, LH, FSH and T increased significantly in the OBC group (P<0.05). There was a significant increase in the transcriptional levels of Adipo, Adipo receptor 1 (Adipo R1), and AMP-activated protein kinase (AMPK) in the OBC group (P<0.05) compared to in the CON group; meanwhile, the transcriptional levels of kisspeptin (Kiss) and gonadotropin-releasing hormone (GnRH) decreased significantly (P<0.05). In conclusion, long-term moderate-intensity exercise could improve the negative effect of obesity on sex development. Long-term high-intensity exercises could not improve the inhibitory effect of obesity on sex development.


Assuntos
Hormônios Esteroides Gonadais/sangue , Hipotálamo/metabolismo , Obesidade/genética , Condicionamento Físico Animal , Adenilato Quinase/metabolismo , Adiponectina/sangue , Animais , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Hormônio Luteinizante/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Distribuição Aleatória , Testosterona/sangue
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