Felipe F Casanueva

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Santiago, Galicia, Spain

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Publications (604)2119.57 Total impact

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    ABSTRACT: The restoration of body composition (BC) parameters is considered to be one of the most important goals in the treatment of patients with anorexia nervosa (AN). However, little is known about differences between AN diagnostic subtypes [restricting (AN-R) and binge/purging (AN-BP)] and weekly changes in BC during refeeding treatment. Therefore, the main objectives of our study were twofold: 1) to assess the changes in BC throughout nutritional treatment in an AN sample and 2) to analyze predictors of BC changes during treatment, as well as predictors of treatment outcome. The whole sample comprised 261 participants [118 adult females with AN (70 AN-R vs. 48 AN-BP), and 143 healthy controls]. BC was measured weekly during 15 weeks of day-hospital treatment using bioelectrical impedance analysis (BIA). Assessment measures also included the Eating Disorders Inventory-2, as well as a number of other clinical indices. Overall, the results showed that AN-R and AN-BP patients statistically differed in all BC measures at admission. However, no significant time×group interaction was found for almost all BC parameters. Significant time×group interactions were only found for basal metabolic rate (p = .041) and body mass index (BMI) (p = .035). Multiple regression models showed that the best predictors of pre-post changes in BC parameters (namely fat-free mass, muscular mass, total body water and BMI) were the baseline values of BC parameters. Stepwise predictive logistic regressions showed that only BMI and age were significantly associated with outcome, but not with the percentage of body fat. In conclusion, these data suggest that although AN patients tended to restore all BC parameters during nutritional treatment, only AN-BP patients obtained the same fat mass values as healthy controls. Put succinctly, the best predictors of changes in BC were baseline BC values, which did not, however, seem to influence treatment outcome.
    PLoS ONE 11/2015; 10(11):e0143012. DOI:10.1371/journal.pone.0143012 · 3.23 Impact Factor
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    ABSTRACT: The gut-brain axis is of great importance in the control of energy homeostasis. The identification of uroguanylin (UGN), an intestinal released peptide regulated by nutritional status and with anorectic actions, as the endogenous ligand for guanylyl cyclase 2C (GUCY2C) receptor, has revealed a new system in the regulation of energy balance. We show that chronic central infusion of uroguanylin (UGN) reduces weight gain and adiposity in diet-induced obese mice. These effects were independent of food intake and involved specific efferent autonomic pathways. On one hand, brain UGN induces brown adipose tissue thermogenesis as well as browning and lipid mobilization in white adipose tissue through stimulation of the sympathetic nervous system. On the other hand, brain UGN augments fecal output through the vagus nerve. These findings are of relevance as they suggest that the beneficial metabolic actions of UGN through the sympathetic nervous system do not involve non-desirable gastrointestinal adverse effects, such as diarrhea. The present work provides mechanistic insights on how UGN influences energy homeostasis and suggests that UGN action in the brain represents a feasible pharmacological target in the treatment of obesity.
    Diabetes 11/2015; DOI:10.2337/db15-0889 · 8.10 Impact Factor

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    ABSTRACT: BACKGROUND/OBJECTIVES Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could play 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. Additionally, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (RPAT) or subcutaneous (SAT) adipose tissue secretome and with rising concentrations of the lipid peroxidation by-product 4-HNE.RESULTSDIO 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.CONCLUSION 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.International Journal of Obesity accepted article preview online, 07 October 2015. doi:10.1038/ijo.2015.208.
    International journal of obesity (2005) 10/2015; DOI:10.1038/ijo.2015.208 · 5.00 Impact Factor
  • A B Crujeiras · M A Zulet · I Abete · M Amil · M C Carreira · J A Martínez · F F Casanueva ·
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    ABSTRACT: CONTEXTThe 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 features under energy-restricted weight-loss programs and in normal weight in order to stablish 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 and forty three participants were enrolled in the study (95 obese-metabolic syndrome; age 49.5±9.4 y.o; BMI 35.7±4.5 kg/m(2)/48 normal-weight; age 35.71±8.8 y.o; 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 diet, a novel dietary program with changes in the macronutrient distribution) was only prescribed to obese-metabolic syndrome participants who were randomly allocated to the dietary strategies. Dietary records, anthropometrical and biochemical variables as well as betatrophin levels were analysed before (pre-intervention, wk 0), at 8 weeks (post-intervention, wk 8) and after 4 additional months of self-control period (follow-up, wk 24).RESULTSBetatrophin levels were higher in obese-metabolic syndrome patients than normal-weight subjects (1.24±0.43 ng/ml vs. 0.97±0.69 ng/ml, 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 (wk0) 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 metabolic syndrome 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.International Journal of Obesity accepted article preview online, 07 October 2015. doi:10.1038/ijo.2015.206.
    International journal of obesity (2005) 10/2015; DOI:10.1038/ijo.2015.206 · 5.00 Impact Factor
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    ABSTRACT: The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.
    Frontiers in Psychology 09/2015; 6. DOI:10.3389/fpsyg.2015.01431 · 2.80 Impact Factor
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    ABSTRACT: Purpose: The SAGIT instrument is a comprehensive clinician-reported outcome instrument assessing key features of acromegaly: signs and symptoms, associated comorbidities; growth hormone levels; insulin-like growth factor-1 levels; and tumor profile. The SAGIT instrument has been designed to assist endocrinologists managing acromegaly in practice. Here, we report on pre-testing (to assess ease of understanding and acceptability) and a pilot study (to assess relevance, ease of use, and utility in real-life conditions) (NCT02231593). Methods: For pre-testing, 11 endocrinologists completed the SAGIT instrument using patient medical records and were also interviewed. They subsequently completed a PRAgmatic Content and face validity Test (PRAC-Test(©)) to report their experiences using SAGIT, and feedback was used to revise the instrument. In the pilot study, nine endocrinologists completed the SAGIT instrument in real-time with patients belonging to three different categories (stable/controlled, active/uncontrolled acromegaly, treatment-naïve), while four completed the instrument based on medical-record review. All participants then completed the PRAC-Test(©) and their feedback was used to update the instrument. Results: The SAGIT instrument was well accepted by endocrinologists, with most indicating that it was concise, practical, easy to understand, useful for assessing treatment response, and valuable as a component of the patient's medical record. The pilot study confirmed the instrument's acceptability, utility, and ease of use, and indicated its potential for distinguishing acromegaly clinical stages. Conclusions: The SAGIT instrument is promising as a tool for use by endocrinologists in everyday practice to assess the status and evolution of disease in patients with acromegaly and to guide treatment decision-making.
    Pituitary 09/2015; DOI:10.1007/s11102-015-0681-2 · 3.20 Impact Factor

  • Age and Ageing 09/2015; 44(suppl 2). DOI:10.1093/ageing/afv112.03 · 3.64 Impact Factor

  • Leuven Epidemiology Symposium; 09/2015
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    ABSTRACT: Hypoglycemia is a limiting factor in the achievement of strict glycemic control. The primary objective of this 9-week study was to determine the frequency of hypoglycemia in patients with stable insulin-treated type 2 diabetes mellitus by comparing self-monitored blood glucose (SMBG) measurement with continuous glucose monitoring (CGM). This was an observational prospective study. Included in the study were 63 stable, insulin-treated patients with type 2 diabetes. They were instructed to record 2 daily capillary blood glucose readings, pre- and/or postprandial, in a sequential way during 8 consecutive weeks. A CGM system was worn during an additional week. We evaluated the frequency of hypoglycemia using the 8-week SMBG profile and the 1 CGM week. SMBG revealed that 50% of the patients had experienced hypoglycemia. CGM found hypoglycemia in 59% of patients. Significantly higher percentages of hyperglycemic and hypoglycemic episodes were detected by CGM than by capillary blood glucose measurements (61.1% vs. 50.8%; p=0.047) and (3.8% vs. 1.7%; p=0.016); 33% of patients experienced nocturnal hypoglycemia, and 19% of patients who had no data concerning hypoglycemia recorded in the capillary blood glucose diary had experienced hypoglycemia as measured by CGM, and the hypoglycemia occurred mainly during the nocturnal period. In stable well-controlled, insulin-treated patients with type 2 diabetes, CGM showed higher numbers of hypoglycemic events than did SMBG, especially at night. CGM is a useful tool that provides clinically valuable information about glucose control in these patients. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.
    08/2015; 39(5). DOI:10.1016/j.jcjd.2015.05.007
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    ABSTRACT: Obestatin/GPR39 signaling stimulates skeletal muscle repair by inducing the expansion of satellite stem cells as well as myofiber hypertrophy. Here, we describe that the obestatin/GPR39 system acts as autocrine/paracrine factor on human myogenesis. Obestatin regulated multiple steps of myogenesis: myoblast proliferation, cell cycle exit, differentiation and recruitment to fuse and form multinucleated hypertrophic myotubes. Obestatin-induced mitogenic action was mediated by ERK1/2 and JunD activity, being orchestrated by a G-dependent mechanism. At a later stage of myogenesis, scaffolding proteins β-arrestin 1 and 2 were essential for the activation of cell cycle exit and differentiation through the transactivation of the epidermal growth factor receptor (EGFR). Upon obestatin stimulus, β-arrestins are recruited to the membrane, where they functionally interact with GPR39 leading to Src activation and signalplex formation to EGFR transactivation by matrix metalloproteinases. This signalplex regulated the mitotic arrest by p21 and p57 expression and the mid- to late stages of differentiation through JNK/c-Jun, CAMKII, Akt and p38 pathways. This finding not only provides the first functional activity for β-arrestins in myogenesis but also identify potential targets for therapeutic approaches by triggering specific signaling arms of the GPR39 signaling involved in myogenesis.
    Cellular and Molecular Life Sciences CMLS 07/2015; DOI:10.1007/s00018-015-1994-z · 5.81 Impact Factor
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    ABSTRACT: (1) The objective of this study is to analyze differences in smell-taste capacity between females in extreme weight/eating conditions (EWC) and (2) to explore the interaction between smell/taste capacity, gastric hormones, eating behavior and body mass index (BMI). The sample comprised 239 females in EWC [64 Anorexia nervosa (AN) and 80 age-matched healthy-weight controls, and 59 obese and 36 age-matched healthy-weight controls]. Smell and taste assessments were performed through "Sniffin' Sticks" and "Taste Strips," respectively. The assessment measures included the eating disorders inventory-2, the symptom check list 90-revised, and The Dutch Eating Behavior Questionnaire, as well as peptides from the gastrointestinal tract [Ghrelin, peptide YY, cholecystokinin]. Smell capacity was differentially associated across EWC groups. Smell was clearly impaired in obese participants and increased in AN (hyposmia in Obesity was 54.3 and 6.4 % in AN), but taste capacity did not vary across EWC. Ghrelin levels were significantly decreased in obese subjects and were related to smell impairment. EWC individuals showed a distinct smell profile and circulating ghrelin levels compared to controls. Smell capacity and ghrelin may act as moderators of emotional eating and BMI.
    Endocrine 07/2015; DOI:10.1007/s12020-015-0684-9 · 3.88 Impact Factor
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    ABSTRACT: Betatrophin is produced primarily by liver and adipose tissue, and has been recently reported as a novel hormone promoting β cell proliferation and β cell mass and improving glucose tolerance. Since it is markedly regulated by nutritional status, we hypothesized that circulating betatrophin levels might be affected by pathophysiological conditions altering body weight. We analyzed circulating betatrophin levels in 149 female patients, including 99 with extremeBMI(30 anorexia nervosa,24obese,45morbidobeseand50healthy eating/weight controls). Measurements. Serum betatrophin levels and its correlations with different anthropometric and biochemical parameters. Plasma betatrophin levels were significantly elevated in anorexic patients, whereas its levels were reduced in morbid obese women when compared to normal weight women. Plasma betatrophin correlated negatively with weight, BMI, fat percentage, glucose, insulin, HOMA and positively correlated with HDL. These results suggest that metabolic status is an important regulator of circulating betatrophin levels.
    The Journal of Clinical Endocrinology and Metabolism 07/2015; 100(9):JC20151595. DOI:10.1210/JC.2015-1595 · 6.21 Impact Factor
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    ABSTRACT: low bone mineral density measured by dual-energy x-ray absorptiometry is associated with increased mortality. The relationship between other skeletal phenotypes and mortality is unclear. The aim of this study was to determine the relationship between quantitative heel ultrasound parameters and mortality in a cohort of European men. men aged 40-79 years were recruited for participation in a prospective study of male ageing: the European Male Ageing Study (EMAS). At baseline, subjects attended for quantitative ultrasound (QUS) of the heel (Hologic-SAHARA) and completed questionnaires on lifestyle factors and co-morbidities. Height and weight were measured. After a median of 4.3 years, subjects were invited to attend a follow-up assessment, and reasons for non-participation, including death, were recorded. The relationship between QUS parameters (broadband ultrasound attenuation [BUA] and speed of sound [SOS]) and mortality was assessed using Cox proportional hazards model. from a total of 3,244 men (mean age 59.8, standard deviation [SD] 10.8 years), 185 (5.7%) died during the follow-up period. After adjusting for age, centre, body mass index, physical activity, current smoking, number of co-morbidities and general health, each SD decrease in BUA was associated with a 20% higher risk of mortality (hazard ratio [HR] per SD = 1.2; 95% confidence interval [CI] = 1.0-1.4). Compared with those in higher quintiles (2nd-5th), those in the lowest quintile of BUA and SOS had a greater mortality risk (BUA: HR = 1.6; 95% CI = 1.1-2.3 and SOS: HR = 1.6; 95% CI = 1.2-2.2). lower heel ultrasound parameters are associated with increased mortality in European men. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society.
    Age and Ageing 07/2015; 44(5). DOI:10.1093/ageing/afv073 · 3.64 Impact Factor
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    ABSTRACT: Background Diabetes has been defined on the basis of different bio-markers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA1c. We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the bio-markers used for defining diabetes. Diabetes was defined using HbA1c (HbA1c ≥6·5% or history of diabetes diagnosis or using insulin or oral hypoglycemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG ≥7·0 mmol/L or 2hOGTT ≥11·1 mmol/L or history of diabetes or using insulin or oral hypoglycemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (i.e., excluding those with history of diabetes or using insulin or oral hypoglycemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG-or-2hOGTT was correlated with prevalence based on FPG alone (r=0·98), but was higher by 2–6 percentage points at different prevalence levels. Prevalence based on HbA1c was lower than prevalence based on FPG in 42·8% of age–sex–survey groups and higher in another 41·6%; in the other 15·6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA1c-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, sub-national, or from specific communities. Diabetes defined as HbA1c 6·5% or more had a pooled sensitivity of 52·8% (95% CI 51·3–54·3%) and a pooled specificity of 99·74% (99·71–99·78%) compared with FPG 7·0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30·5% (28·7–32·3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA1c versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA1c-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
    The Lancet Diabetes & Endocrinology 06/2015; DOI:10.1016/S2213-8587(15)00129-1 · 9.19 Impact Factor
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    ABSTRACT: In the context of obesity, strong evidences support a distinctive pathological contribution of adipose tissue depending on its anatomical site of accumulation. Therefore, subcutaneous adipose tissue (SAT), has been lately considered metabolically benign compared to visceral fat (VAT) whose location is associated to the risk of developing cardiovascular disease, insulin resistance, and other associated comorbidities. Under the above situation, the chronic local inflammation that characterizes obese adipose tissue, has acquired a major role on the pathogenesis of obesity. In this work, we have analyzed for the first time human obese VAT and SAT secretomes using an improved quantitative proteomic approach for the study of tissue secretomes, comparison of isotope-labeled amino acid incorporation rates (CILAIR). The use of double isotope-labeling-CILAIR approach to analyze VAT and SAT secretomes allowed the identification of location-specific secreted proteins and its differential secretion. Additionally to the very high percentage of identified proteins previously implicated in obesity or in its comorbidities, this approach was revealed as an useful tool for the study of the obese adipose tissue microenvironment including extracellular matrix (ECM) remodeling and inflammatory status. The results herein presented reinforce the fact that VAT and SAT depots have distinct features and contribute differentially to metabolic disease.
    Scientific Reports 06/2015; 5. DOI:10.1038/srep12214 · 5.58 Impact Factor
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    ABSTRACT: The prefrontal (PFC) and orbitofrontal cortex (OFC) appear to be associated with both executive functions and olfaction. However, there is little data relating olfactory processing and executive functions in humans. The present study aimed at exploring the role of olfaction on executive functioning, making a distinction between primary and more cognitive aspects of olfaction. Three executive tasks of similar difficulty were used. One was used to assess hot executive functions (Iowa Gambling Task-IGT), and two as a measure of cold executive functioning (Stroop Colour and Word Test-SCWT and Wisconsin Card Sorting Test-WCST). Sixty two healthy participants were included: 31 with normosmia and 31 with hyposmia. Olfactory abilities were assessed using the ''Sniffin' Sticks'' test and the olfactory threshold, odour discrimination and odour identification measures were obtained. All participants were female, aged between 18 and 60. Results showed that participants with hyposmia displayed worse performance in decision making (IGT; Cohen's-d = 0.91) and cognitive flexibility (WCST; Cohen's-d between 0.54 and 0.68) compared to those with normosmia. Multiple regression adjusted by the covariates participants' age and education level showed a positive association between odour identification and the cognitive inhibition response (SCWT-interference; Beta = 0.29; p = .034). The odour discrimination capacity was not a predictor of the cognitive executive performance. Our results suggest that both hot and cold executive functions seem to be associated with higher-order olfactory functioning in humans. These results robustly support the hypothesis that olfaction and executive measures have a common neural substrate in PFC and OFC, and suggest that olfaction might be a reliable cognitive marker in psychiatric and neurologic disorders.
    PLoS ONE 06/2015; 10(6):e0130319. DOI:10.1371/journal.pone.0130319 · 3.23 Impact Factor
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    ABSTRACT: Secondary hypogonadism is common in ageing men; its natural history and predisposing factors are unclear. 1) To identify factors which predispose eugonadal men (T ≥10.5nmol/L) to develop biochemical secondary hypogonadism (T<10.5nmol/L, LH≤9.4U/L) and secondary hypogonadal men to recover to eugonadism. 2) To characterize clinical features associated with these transitions. Prospective observational general population cohort survey. Clinical research centres. 3369 community-dwelling men aged 40-79 yr in eight European centres. Observational follow-up of 4.3 years. Subjects were categorised according to change/no change in biochemical gonadal status during follow-up into persistent eugonadal (n=1909), incident secondary hypogonadal (n=140), persistent secondary hypogonadal (n=123) and recovered from secondary hypogonadism to eugonadism (n=96). Baseline predictors and changes in clinical features associated with incident secondary hypogonadism and recovery from secondary hypogonadism were analysed by regression models. The incidence of secondary hypogonadism was 155.9/10,000/year, while 42.9% of men with secondary hypogonadism recovered to eugonadism. Incident secondary hypogonadism was predicted by obesity [BMI≥30kg/m(2): odds ratio (OR)=2.86 (95% confidence interval 1.67;4.90); p<0.0001], weight gain [OR=1.79 (1.15;2.80);p=0.011] and increased waist circumference [OR=1.73 (1.07;2.81); p=0.026 and 2.64 (1.66;4.21);p<0.0001, for waist circumference 94-102 and ≥102 cm, respectively]. Incident secondary hypogonadal men experienced new/worsening sexual symptoms [low libido, erectile dysfunction and infrequent spontaneous erections]. Recovery from secondary hypogonadism was predicted by non-obesity [OR=2.28 (1.21;4.31); p=0.011], weight loss [OR=2.24 (1.04;4.85); p=0.042], normal waist circumference [OR=1.93 (1.01;3.70); p=0.048], younger age [<60yr OR=2.32 (1.12;4.82); p=0.024] and higher education [OR=2.11 (1.05;4.26); p=0.037], but symptoms did not show significant concurrent improvement. Obesity-related metabolic and lifestyle factors predispose older men to the development of secondary hypogonadism, which is frequently reversible with weight loss.
    The Journal of Clinical Endocrinology and Metabolism 05/2015; 100(8):jc20151571. DOI:10.1210/jc.2015-1571 · 6.21 Impact Factor
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    ABSTRACT: Leptin is an adipocyte-secreted hormone that inhibits food intake and stimulates energy expenditure through interactions with neuronal pathways in the brain, particularly pathways involving the hypothalamus. Intact functioning of the leptin route is required for body weight and energy homeostasis. Given its function, the discovery of leptin increased expectations for the treatment of obesity. However, most obese individuals and subjects with a predisposition to regain weight after losing it have leptin concentrations than lean individuals, but despite the anorexigenic function of this hormone, appetite is not effectively suppressed in these individuals. This phenomenon has been deemed leptin resistance and could be the result of impairments at a number of levels in the leptin signalling pathway, including reduced access of the hormone to its receptor due to changes in receptor expression or changes in post-receptor signal transduction. Epigenetic regulation of the leptin signalling circuit could be a potential mechanism of leptin function disturbance. This review discusses the molecular mechanisms, particularly the epigenetic regulation mechanisms, involved in leptin resistance associated with obesity and the therapeutic potential of these molecular mechanisms in the battle against the obesity pandemic. Copyright © 2015. Published by Elsevier Inc.
    Life sciences 05/2015; 140. DOI:10.1016/j.lfs.2015.05.003 · 2.70 Impact Factor

Publication Stats

21k Citations
2,119.57 Total Impact Points


  • 2014-2015
    • Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y la Nutrición (CIBERobn)
      Santiago, Galicia, Spain
  • 2009-2015
    • Instituto de Salud Carlos III
      • CIBER of Epidemiology and Public Health (CIBERESP)
      Madrid, Madrid, Spain
  • 1996-2015
    • Complejo Hospitalario Universitario de Santiago
      • Department of Medicine
      Santiago, Galicia, Spain
  • 1985-2015
    • University of Santiago de Compostela
      • • Department of Medicine
      • • Department of Physiology
      Santiago, Galicia, Spain
  • 2008-2012
    • Imperial College London
      • Department of Surgery and Cancer
      London, ENG, United Kingdom
    • University of Oxford
      • Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM)
      Oxford, ENG, United Kingdom
  • 2011
    • University of Florence
      • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      Florens, Tuscany, Italy
    • Instituto de Investigación Sanitaria de Santiago de Compostela
      Santiago, Galicia, Spain
  • 1990-2008
    • Hospital Universitario Virgen del Rocío
      • Division of Endocrinology
      Hispalis, Andalusia, Spain
    • Hospital Universitario Cruces
      Bilbo, Basque Country, Spain
  • 2007
    • Hospital General Universitario Gregorio Marañón
      Madrid, Madrid, Spain
    • Klinički centar Srbije
      • Institute of Endocrinology, Diabetes and Diseases of Metabolism
      Beograd, Central Serbia, Serbia
  • 1999-2006
    • Santiago University of Technology
      Santiago, Santiago, Dominican Republic
  • 1991-2004
    • University of Santiago, Chile
      • Departamento Clínico de Medicina Interna
      CiudadSantiago, Santiago Metropolitan, Chile
  • 2003
    • University of A Coruña
      • Department of Medicine
      La Corogne, Galicia, Spain
  • 1980-2002
    • University of Milan
      • Department of Pharmacology, Chemotherapy and Medical Toxicology
      Milano, Lombardy, Italy
  • 1993
    • University of Belgrade
      • Institute of Endocrinology
      Belgrade, SE, Serbia
  • 1981-1986
    • Complutense University of Madrid
      • Department of Medicine
      Madrid, Madrid, Spain