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1.
Eur J Endocrinol ; 182(1): 11-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31652416

RESUMO

Objective: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). Results: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. Conclusions: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.

2.
Eur J Endocrinol ; 182(1): G1-G32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855556

RESUMO

Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.


Assuntos
Índice de Massa Corporal , Hipotireoidismo/diagnóstico , Obesidade/diagnóstico , Comorbidade , Endocrinologia , Humanos , Hipotireoidismo/epidemiologia , Obesidade/epidemiologia , Prevalência , Testes de Função Tireóidea
3.
BMC Med Genomics ; 12(1): 72, 2019 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133015

RESUMO

BACKGROUND/OBJECTIVES: Obesity has been associated with gene methylation regulation. Recent studies have shown that epigenetic signature plays a role in metabolic homeostasis after Roux-en Y gastric bypass (RYGB). To conduct a genome-wide epigenetic analysis in peripheral blood to investigate whether epigenetic changes following RYGB stem from weight loss or the surgical procedure per se. SUBJECTS/METHODS: By means of the Infinium Human Methylation 450 BeadChip array, global methylation was analyzed in blood of 24 severely obese women before and 6 months after RYGB and in 24 normal-weight women (controls). RESULTS: In blood cells, nine DMCpG sites showed low methylation levels before surgery, methylation levels increased after RYGB and neared the levels measured in the controls. Additionally, 44 CpG sites associated with the Wnt and p53 signaling pathways were always differently methylated in the severely obese patients as compared to the controls and were not influenced by RYGB. Finally, 1638 CpG sites related to inflammation, angiogenesis, and apoptosis presented distinct methylation in the post-surgery patients as compared to the controls. CONCLUSION: Bariatric surgery per se acts on CpGs related to inflammation, angiogenesis, and endothelin-signaling. However, the gene cluster associated with obesity remains unchanged, suggesting that weight loss 6 months after RYGB surgery cannot promote this effect.


Assuntos
Metilação de DNA , Epigênese Genética , Derivação Gástrica , Adulto , Peso Corporal/genética , Ilhas de CpG/genética , Feminino , Humanos , Masculino , Obesidade/genética , Obesidade/cirurgia , Fenótipo , Fatores de Tempo
4.
J Mol Endocrinol ; 60(2): R31-R38, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29203517

RESUMO

Uroguanylin (UGN) is a potential target in the fight against obesity. The mature protein is released after enzymatic cleavage from its natural precursor, proUGN. UGN is mostly produced in the gut, and its production is regulated by nutritional status. However, UGN is also produced in other tissues such as the kidneys. In the past, UGN has been widely studied as a natriuretic peptide owing to its involvement in several different pathologies such as heart failure, cancer and gastrointestinal diseases. However, recent studies have suggested that UGN also acts as a regulator of body weight homeostasis because it modulates both food intake and energy expenditure. This ultimately results in a decrease in body weight. This action is mediated by the sympathetic nervous system. Future studies should be directed at the potential effects of UGN agonists in regulating body weight in human obesity.


Assuntos
Metabolismo Energético , Peptídeos Natriuréticos/metabolismo , Animais , Metabolismo Energético/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Humanos , Intestinos/efeitos dos fármacos , Modelos Biológicos , Peptídeos Natriuréticos/administração & dosagem , Peptídeos Natriuréticos/biossíntese , Peptídeos Natriuréticos/farmacologia
5.
Sci Rep ; 7(1): 16289, 2017 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-29176631

RESUMO

Irisin is a browning-stimulating molecule secreted from the fibronectin type III domain containing 5 precursor (FNDC5) by muscle tissue upon exercise stimulation. Despite its beneficial role, there is an unmet and clamorous need to discern many essential aspects of this protein and its mechanism of action not only as a myokine but also as an adipokine. Here we contribute to address this topic by revealing the nature and role of FNDC5/irisin in adipose tissue. First, we show that FNDC5/irisin expression and secretion are induced by adipocyte differentiation and confirm its over-secretion by human obese visceral (VAT) and subcutaneous (SAT) adipose tissues. Second, we show how secreted factors from human obese VAT and SAT decrease PGC1α, FNDC5 and UCP1 gene expression on differentiating adipocytes; this effect over UCP1 is blunted by blocking irisin in obese secretomes. Finally, by stable gene silencing FNDC5 we reveal that FNDC5-KO adipocytes show reduced UCP1 expression and enhanced adipogenesis.


Assuntos
Adipócitos/metabolismo , Adipogenia/fisiologia , Fibronectinas/metabolismo , Termogênese/fisiologia , Proteína Desacopladora 1/metabolismo , Adipogenia/genética , Animais , Fibronectinas/genética , Inativação Gênica/fisiologia , Humanos , Gordura Intra-Abdominal/metabolismo , Camundongos , Obesidade/genética , Obesidade/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Gordura Subcutânea/metabolismo , Termogênese/genética , Proteína Desacopladora 1/genética
6.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 44(3): 129-133, jul.-sept. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-164933

RESUMO

Los tumores de ovario de células esteroideas constituyen una entidad infrecuente de virilización. Pueden originarse del estoma o de los cordones sexuales; en ocasiones el linaje tumoral es desconocido, denominándose tumor esteroide no especificado. Presentamos el caso de una paciente con signos de virilización rápidamente progresiva, sugestivo de origen ovárico. Las pruebas de imágenes fueron negativas, y tras ser sometida a intervención quirúrgica se objetivó la presencia de un tumor microscópico con marcadores positivos para células esteroideas


Ovarian steroid cell tumours are an uncommon cause of virilisation. They may originate from the stroma or sex cords; sometimes the tumour lineage is unknown, in which case the tumour is described as ‘not otherwise specified’. We report the case of a patient with signs of rapidly progressive virilisation, suggestive of ovarian origin. Imaging tests were negative. After surgical intervention, the presence of microscopic tumour markers positive for steroid cells was observed


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Hormônios Esteroides Gonadais , Virilismo/fisiopatologia , Hiperandrogenismo/etiologia , Alopecia/etiologia , Histerectomia , Ovariectomia
7.
Int J Obes (Lond) ; 41(10): 1570-1578, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28588304

RESUMO

BACKGROUND: Fibroblast growth factor 21 (FGF21) has been suggested to be an endocrine signal of nutritional status and an active regulator of metabolism. However, there is no agreement on the effect of weight-loss therapies on circulating levels of FGF21 in humans. OBJECTIVE: To assess FGF21 circulating levels in adiposity excess and after different weight-loss strategies prescribed in five different groups from four independent centers. SUBJECTS AND METHODS: Body composition, ketosis, insulin sensitivity and FGF21 were evaluated in 181 excess body weight and 14 normal-weight subjects. From the excess body weight patients, two independent groups (discovery cohort; n=20 and validation cohort; n=28) undertook a very low-calorie ketogenic (VLCK) diet, a third group followed a low-calorie (LC) diet (n=84) and other two groups underwent bariatric surgery (discovery cohort; n=24 and validation cohort; n=25). The follow-up was 4 to 6 or 12 months, respectively. RESULTS: FGF21 levels were higher in excess body weight patients than in normal-weight subjects. The energy-restriction therapy to lose weight induced a significant decrease, with respect to baseline, in circulating levels of FGF21 (VLCK: -62.5 pg ml-1 or -14.8 pg ml-1 and LC diet: -67.9 pg ml-1). There were no differences in FGF21 levels between both energy-restriction treatments. On the contrary, after bariatric surgery morbidly obese patients showed a significant increase in FGF21, especially 1 month after surgery (148.8 pg ml-1 higher than baseline). The FGF21 differential changes occur concomitantly with a non-induced ketosis situation (0.66±0.56 mm) in bariatric surgery, and an improvement in adiposity and insulin sensitivity induced by the three therapies. CONCLUSIONS: FGF21 levels were reduced after energy-restricted treatments and severely increased after bariatric surgery, independently of the weight reduction magnitude, insulin sensitivity or ketosis. Therefore, FGF21 appears to be a marker of severe nutritional stress.


Assuntos
Cirurgia Bariátrica , Restrição Calórica , Fatores de Crescimento de Fibroblastos/sangue , Obesidade Mórbida/sangue , Obesidade Mórbida/terapia , Estresse Fisiológico , Adulto , Biomarcadores/sangue , Composição Corporal , Feminino , Seguimentos , Humanos , Resistência à Insulina , Cetose , Masculino , Estado Nutricional/fisiologia , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Espanha , Perda de Peso
8.
Sci Rep ; 7: 41903, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28211912

RESUMO

The characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip. Data were compared between samples from obese (n = 45) and non-obese (n = 8-10) patients by Wilcoxon-rank test, unadjusted for cell type distributions. A global hypomethylation of the differentially methylated CpG sites (DMCpGs) was observed in the obese subcutaneous adipose tissue and leukocytes. The overlap analysis yielded a number of genes mapped by the common DMCpGs that were identified to reflect the obesity state in the leukocytes. Specifically, the methylation levels of FGFRL1, NCAPH2, PNKD and SMAD3 exhibited excellent and statistically significant efficiencies in the discrimination of obesity from non-obesity status (AUC > 0.80; p < 0.05) and a great correlation between both tissues. Therefore, the current study provided new and valuable DNA methylation biomarkers of obesity-related adipose tissue pathogenesis through peripheral blood analysis, an easily accessible and minimally invasive biological material instead of adipose tissue.


Assuntos
Metilação de DNA , Leucócitos/metabolismo , Obesidade/genética , Gordura Subcutânea/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ilhas de CpG , Feminino , Genoma Humano , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/genética , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/genética , Serina Endopeptidases/genética , Proteína Smad3/genética
9.
Nutr Diabetes ; 6(9): e230, 2016 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-27643725

RESUMO

UNLABELLED: Brackground:The safety and tolerability of very low-calorie-ketogenic (VLCK) diets are a current concern in the treatment of obese type 2 diabetes mellitus (T2DM) patients. OBJECTIVE: Evaluating the short-term safety and tolerability of a VLCK diet (<50 g of carbohydrate daily) in an interventional weight loss program including lifestyle and behavioral modification support (Diaprokal Method) in subjects with T2DM. METHODS: Eighty-nine men and women, aged between 30 and 65 years, with T2DM and body mass index between 30 and 35 kg m(-)(2) participated in this prospective, open-label, multi-centric randomized clinical trial with a duration of 4 months. Forty-five subjects were randomly assigned to the interventional weight loss (VLCK diet), and 44 to the standard low-calorie diet. RESULTS: No significant differences in the laboratory safety parameters were found between the two study groups. Changes in the urine albumin-to-creatinine ratio in VLCK diet were not significant and were comparable to control group. Creatinine and blood urea nitrogen did not change significantly relative to baseline nor between groups. Weight loss and reduction in waist circumference in the VLCK diet group were significantly larger than in control subjects (both P<0.001). The decline in HbA1c and glycemic control was larger in the VLCK diet group (P<0.05). No serious adverse events were reported and mild AE in the VLCK diet group declined at last follow-up. CONCLUSIONS: The interventional weight loss program based on a VLCK diet is most effective in reducing body weight and improvement of glycemic control than a standard hypocaloric diet with safety and good tolerance for T2DM patients.


Assuntos
Restrição Calórica , Diabetes Mellitus Tipo 2/terapia , Dieta Cetogênica , Dieta Redutora , Programas de Redução de Peso/métodos , Adulto , Idoso , Terapia Comportamental , Glicemia/análise , Restrição Calórica/efeitos adversos , Dieta Cetogênica/efeitos adversos , Dieta Redutora/efeitos adversos , Feminino , Hemoglobina A Glicada/análise , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Circunferência da Cintura , Perda de Peso
10.
Sci Rep ; 6: 30820, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27476477

RESUMO

Whether the executive profile is different between obesity (OB) and morbid obesity (MO) remains unclear. Recent evidence suggests that physical activity (PA) can act as a cognitive enhancer. Irisin is a recently discovered hormone associated with some of the positive effects of PA. The objective of the study was to investigate the executive profile in OB and MO, and to explore the role of PA and irisin. 114 participants were included (21 OB, 44 MO and 49 healthy controls-HC) in the study and assessed with the Wisconsin Card Sorting Test, Stroop Color and Word Test, and Iowa Gambling Task. All participants were female, aged between 18 and 60 years. Results showed a similar dysfunctional profile on decision making in OB and MO compared with HC. Thus, no specific neuropsychological profiles between OB and MO can be clearly observed in our sample. However, a negative correlation was found between irisin and executive functioning. These results demonstrate a specific executive profile in OB and a relevant and negative modulation of irisin on executive functioning. Although irisin might be a promising target for the treatment of obesity, its effects on cognition might be considered when thinking about its therapeutic use.


Assuntos
Exercício , Fibronectinas/metabolismo , Obesidade Mórbida , Adolescente , Adulto , Tomada de Decisões , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/psicologia
11.
Transl Res ; 178: 13-24.e5, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27477082

RESUMO

Elucidating the potential mechanisms involved in the detrimental effect of excess body weight on insulin action is an important priority in counteracting obesity-associated diseases. The present study aimed to disentangle the epigenetic basis of insulin resistance by performing a genome-wide epigenetic analysis in visceral adipose tissue (VAT) from morbidly obese patients depending on the insulin sensitivity evaluated by the clamp technique. The global human methylome screening performed in VAT from 7 insulin-resistant (IR) and 5 insulin-sensitive (IS) morbidly obese patients (discovery cohort) analyzed using the Infinium HumanMethylation450 BeadChip array identified 982 CpG sites able to perfectly separate the IR and IS samples. The identified sites represented 538 unique genes, 10% of which were diabetes-associated genes. The current work identified novel IR-related genes epigenetically regulated in VAT, such as COL9A1, COL11A2, CD44, MUC4, ADAM2, IGF2BP1, GATA4, TET1, ZNF714, ADCY9, TBX5, and HDACM. The gene with the largest methylation fold-change and mapped by 5 differentially methylated CpG sites located in island/shore and promoter region was ZNF714. This gene presented lower methylation levels in IR than in IS patients in association with increased transcription levels, as further reflected in a validation cohort (n = 24; 11 IR and 13 IS). This study reveals, for the first time, a potential epigenetic regulation involved in the dysregulation of VAT that could predispose patients to insulin resistance and future type 2 diabetes in morbid obesity, providing a potential therapeutic target and biomarkers for counteracting this process.


Assuntos
Metilação de DNA/genética , Genoma Humano , Resistência à Insulina/genética , Insulina/farmacologia , Gordura Intra-Abdominal/metabolismo , Obesidade Mórbida/genética , Antropometria , Cromossomos Humanos/genética , Estudos de Coortes , Ilhas de CpG/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Gordura Intra-Abdominal/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
12.
Osteoporos Int ; 27(11): 3227-3237, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27273111

RESUMO

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits. INTRODUCTION: Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. METHODS: We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). RESULTS: MetS was present in 975 men (31.2 %). Men with MetS had lower ß C-terminal cross-linked telopeptide (ß-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine aBMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and ß-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip aBMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and ß-CTX, BUA, and radius CSA in BMI-adjusted models. CONCLUSIONS: Men with MetS have higher aBMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS.


Assuntos
Remodelação Óssea , Osso e Ossos/patologia , Hiperglicemia/complicações , Resistência à Insulina , Síndrome Metabólica/complicações , Adulto , Idoso , Envelhecimento , Densidade Óssea , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade
13.
Sci Rep ; 6: 23067, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26961074

RESUMO

The fibronectin type III domain-containing protein 5 (FNDC5) discovered in 2002 has recently gained attention due to its potential role in protecting against obesity. In rat, no data exist regarding FNDC5 production and regulation in the stomach. The aim of the present work was to determine the expression of FNDC5 in the rat stomach and its potential regulation by body composition. The present data shows FNDC5 gene expression in the gastric mucosa. Immunohistochemical studies found FNDC5 immunopositivity in chief cells of gastric tissue. By the use of three different antibodies FNDC5 was found expressed in gastric mucosa and secreted by the stomach. The rate of gastric FNDC5 secretion parallels the circulating levels of FNDC5. The body fat mass increase after intervention with high fat diet coincided with a decrease in the secretion of FNDC5 from the stomach and a diminution in the FNDC5 circulating levels. In summary, the present data shows, for the first time, the expression of FNDC5 in the stomach of rats and its regulation by body composition, suggesting a potential role of gastric FNDC5 in energy homeostasis.


Assuntos
Composição Corporal/genética , Metabolismo Energético/genética , Fibronectinas/biossíntese , Obesidade/genética , Tecido Adiposo/crescimento & desenvolvimento , Tecido Adiposo/metabolismo , Animais , Fibronectinas/genética , Mucosa Gástrica/crescimento & desenvolvimento , Mucosa Gástrica/metabolismo , Regulação da Expressão Gênica , Humanos , Obesidade/metabolismo , Obesidade/patologia , Ratos
14.
Obes Rev ; 17(4): 361-76, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26914773

RESUMO

Obesity, a pandemic disease, is caused by an excessive accumulation of fat that can have detrimental effects on health. Adipose tissue plays a very important endocrine role, secreting different molecules that affect body physiology. In obesity, this function is altered, leading to a dysfunctional production of several factors, known as adipocytokines. This process has been linked to various comorbidities associated with obesity, such as carcinogenesis. In fact, several classical adipocytokines with increased levels in obesity have been demonstrated to exert a pro-carcinogenic role, including leptin, TNF-α, IL-6 and resistin, whereas others like adiponectin, with decreased levels in obesity, might have an anti-carcinogenic function. In this expanding field, new proteomic techniques and approaches have allowed the identification of novel adipocytokines, a number of which exhibit an altered production in obesity and type 2 diabetes and thus are related to adiposity. Many of these novel adipocytokines have also been identified in various tumour types, such as that of the breast, liver or endometrium, thereby increasing the list of potential contributors to carcinogenesis. This review is focused on the regulation of these novel adipocytokines by obesity, including apelin, endotrophin, FABP4, lipocalin 2, omentin-1, visfatin, chemerin, ANGPTL2 or osteopontin, emphasizing its involvement in tumorigenesis.


Assuntos
Tecido Adiposo/metabolismo , Transformação Celular Neoplásica , Neoplasias/etiologia , Obesidade/complicações , Animais , Humanos
15.
Eur J Nutr ; 55(2): 529-536, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25743370

RESUMO

PURPOSE: Uroguanylin (UGN) is a 16 amino acid peptide produced mainly by intestinal epithelial cells. Nutrients intake increases circulating levels of prouroguanylin that is processed and converted to UGN to activate the guanylyl cyclase 2C receptor (GUCY2C). Given that the UGN-GUCY2C system has been proposed as a novel gut-brain endocrine axis regulating energy balance, the aim of the present study was to investigate the regulation of UGN protein levels in duodenum and circulating levels in lean and obese mice under different nutritional conditions and its potential interaction with leptin. METHODS: Swiss, C57BL/6 wild-type and ob/ob male adult mice under different nutritional conditions were used: fed ad libitum standard diet (control); 48 h fasting (fasted); 48 h fasting followed by 24 h of feeding (refed); and fed high-fat diet (45 %) during 10 weeks. In addition, peripheral leptin administration was performed. Intestinal uroguanylin expression was studied by Western blot analysis; plasma levels were measured by ELISA. RESULTS: Food deprivation significantly reduced plasma UGN levels, which were correlated with the lower protein levels of UGN in duodenum. These effects were reverted after refeeding and leptin challenge. Consistently, in ob/ob mice UGN expression was decreased, whereas leptin treatment up-regulated UGN levels in duodenum in these genetically modified mice compared to WT. Diet-induced obese mice displayed increased UGN levels in intestine and plasma in comparison with lean mice. CONCLUSIONS: Our findings suggest that UGN levels are correlated with energy balance status and that the regulation of UGN by nutritional status is leptin-dependent.


Assuntos
Mucosa Intestinal/metabolismo , Leptina/farmacologia , Peptídeos Natriuréticos/sangue , Estado Nutricional , Animais , Dieta Hiperlipídica , Metabolismo Energético , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Peptídeos Natriuréticos/genética , Regulação para Cima
16.
Int J Obes (Lond) ; 40(3): 403-10, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26443337

RESUMO

CONTEXT: The understanding of the potential role of betatrophin in human metabolic disorders is a current challenge. OBJECTIVE: The present research evaluated circulating betatrophin levels in obese patients with metabolic syndrome (MetSyn) features under energy-restricted weight-loss programs and in normal weight in order to establish the putative interplay between the levels of this hormone, diet and metabolic risk factors linked to obesity and associated comorbidities. SUBJECTS AND METHODS: One hundred forty-three participants were enrolled in the study (95 obese-MetSyn; age 49.5±9.4 years; body mass index (BMI) 35.7±4.5 kg m(-2) and 48 normal weight; age 35.71±8.8 years; BMI 22.9±2.2 kg m(-2)). A nutritional therapy consisting in two hypocaloric strategies (control diet based on the AHA recommendations and the RESMENA (MEtabolic Syndrome REduction in Navarra) diet, a novel dietary program with changes in the macronutrient distribution) was only prescribed to obese-MetSyn participants who were randomly allocated to the dietary strategies. Dietary records, anthropometrical and biochemical variables as well as betatrophin levels were analyzed before (pre-intervention, week 0), at 8 weeks (post-intervention, week 8) and after 4 additional months of self-control period (follow-up, week 24). RESULTS: Betatrophin levels were higher in obese-MetSyn patients than normal-weight subjects (1.24±0.43 vs 0.97±0.69 ng ml(-1), respectively, P=0.012), and levels were positively associated with body composition, metabolic parameters, leptin and irisin in all participants at baseline. Notably, low pre-intervention (week 0) betatrophin levels in obese patients were significantly associated with higher dietary-induced changes in atherogenic risk factors after 8 weeks. Moreover, protein intake, especially proteins from animal sources, was an independent determinant of betatrophin levels after dietary treatment (B=-0.27; P=0.012). CONCLUSIONS: Betatrophin is elevated in obese patients with MetSyn features and is associated with poorer nutritional outcomes of adiposity and dyslipidemia traits after a weight-loss program. Dietary protein intake could be a relevant modulator of betatrophin secretion and activity.


Assuntos
Restrição Calórica , Síndrome Metabólica/dietoterapia , Obesidade/dietoterapia , Hormônios Peptídicos/metabolismo , Proteínas Semelhantes a Angiopoietina , Aterosclerose , Biomarcadores/metabolismo , Glicemia/metabolismo , Dieta Redutora , Ingestão de Energia , Feminino , Guias como Assunto , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/prevenção & controle , Resultado do Tratamento , Perda de Peso
17.
Int J Obes (Lond) ; 40(3): 514-23, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26443342

RESUMO

BACKGROUND/OBJECTIVES: Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obese women and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obese women compared with normal weight women without evidence of breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.


Assuntos
Neoplasias da Mama/patologia , Transformação Celular Neoplásica/patologia , Proteínas de Neoplasias/metabolismo , Obesidade/patologia , Gordura Subcutânea/patologia , Animais , Apoptose , Western Blotting , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
18.
Eur Psychiatry ; 30(8): 924-31, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26647868

RESUMO

OBJECTIVE: Elevated physical activity has been observed in some patients with anorexia nervosa (AN) despite their emaciated condition. However, its effects on treatment outcome remain unclear. This study aimed to examine objectively measured physical activity in this clinical population and how it might be related to a partial hospitalization therapy response, after considering potential confounders. METHOD: The sample comprised 88 AN patients consecutively enrolled in a day hospital treatment program, and 116 healthy-weight controls. All participants were female and a baseline assessment took place using an accelerometer (Actiwatch AW7) to measure physical activity, the Eating Disorders Inventory-2 and the Depression subscale of the Symptom Checklist-Revised. Outcome was evaluated upon the termination of the treatment program by expert clinicians. RESULTS: Although AN patients and controls did not differ in the average time spent in moderate-to-vigorous physical activity (MVPA) (P=.21), nor daytime physical activity (P=.34), fewer AN patients presented a high physical activity profile compared to the controls (37% vs. 61%, respectively; P=.014). Both lower levels of MVPA and greater eating disorder severity had a direct effect on a poor treatment outcome. Depression symptoms in the patients were associated with lower MVPA, as well as with an older age, a shorter duration of the disorder and greater eating disorder psychopathology. CONCLUSIONS: There is a notable variation in the physical activity profile of AN patients, characterized by either low or very high patterns. Physical activity is a highly relevant issue in AN that must be taken into account during the treatment process.


Assuntos
Anorexia Nervosa/terapia , Depressão/terapia , Exercício , Satisfação do Paciente , Adolescente , Adulto , Anorexia Nervosa/complicações , Anorexia Nervosa/psicologia , Depressão/complicações , Depressão/psicologia , Feminino , Humanos , Pacientes Internados/psicologia , Masculino , Atividade Motora , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Rev Clin Esp ; 215(9): 505-14, 2015 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26363771

RESUMO

Obesity and excess weight are the main preventable causes of type 2 diabetes (DM2). When diagnosing type 2 diabetes, clinicians should establish the degree of obesity according to the body mass index (BMI) and, for patients with excess weight, measure the waist circumference. The proper treatment of DM2 requires a simultaneous approach to excess weight/obesity and the other cardiovascular risk factors, such as hypertension, dyslipidaemia and smoking. Nondrug interventions (e.g., diet and exercise) have proven benefits in preventing and treating patients with DM2 and excess weight/obesity and should follow an individual and multidisciplinary approach, with structured programs equipped with specific resources. Weight gain associated with antidiabetic treatment can hinder glycaemic control, compromise treatment adherence, worsen the vascular risk profile and limit the cardiovascular benefits of treatment. Therefore, it is significant to avoid weight gain, a measure that can be cost-effective. Antidiabetic drugs with benefits in body weight have also demonstrated their benefit in patients with BMIs <30. In general, the treatment of patients with DM2 and obesity will depend both on the degree of obesity and the associated comorbidity. Clinical trials on DM2 intervention should consider combined objectives that include not only glycaemic control but also other variables such as the risk of hypoglycaemia and the effect of treatment on body weight.

20.
Mol Metab ; 4(6): 437-60, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26042199

RESUMO

BACKGROUND: The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism. SCOPE OF REVIEW: In this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery. MAJOR CONCLUSIONS: In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism.

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