Pituitary tumor centers of excellence for Cushing’s disease

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer NatureS

Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later?

Leptin, a hormone that is capable of effectively reducing food intake and body weight, was initially considered for use in the treatment of obesity. However, obese subjects have since been found to have high levels of circulating leptin and to be insensitive to the exogenous administration of leptin. The inability of leptin to exert its anorexigenic effects in obese individuals, and therefore, the lack of clinical utility of leptin in obesity, is defined as leptin resistance. This phenomenon has not yet been adequately characterized. Elucidation of the molecular mechanisms underlying leptin resistance is of vital importance for the application of leptin as an effective treatment for obesity. Leptin must cross the blood–brain barrier (BBB) to reach the hypothalamus and exert its anorexigenic functions. The mechanisms involved in leptin transportation across the blood–brain barrier continue to be unclear, thereby preventing the clinical application of leptin in the treatment of obesity. In recent years, new strategies have been developed to recover the response to leptin in obesity. We have summarized these strategies in this review.This work was supported by Centro de Investigacion Biomedicaen Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn) and grants from the Instituto de Salud Carlos III (PI17/01287) cofinanced by the European Regional Development Fund (FEDER). Andrea G. Izquierdo and Marcos C Carreira are funded by CIBERobn and Ana B. Crujeiras is funded by a research contract “Miguel Servet” (CP17/00088) from the Instituto de Salud Carlos III, cofinanced by the European Regional Development Fund (FEDER)S

Oxidative Stress Induced by Excess of Adiposity Is Related to a Downregulation of Hepatic SIRT6 Expression in Obese Individuals

Sirt6 is a member of the sirtuin family involved in physiological and pathological processes including aging, cancer, obesity, diabetes, and energy metabolism. This study is aimed at evaluating the relationship between liver SIRT6 gene expression and the oxidative stress network depending on adiposity levels in Zucker rats, an animal model of metabolic syndrome. We observed that liver-specific SIRT6 expression is reduced in an in vivo model of spontaneous obesity and metabolic syndrome. We also observed that SIRT6 expression in the liver is positively associated with SIRT1 and GST-M2 expressions, two proteins involved in antioxidant protection pathways and inversely related to body weight and plasmatic oxidative status. Interestingly, the SIRT6 expression is upregulated after energy restriction-induced weight loss concomitantly with an improvement in oxidative stress markers. These results suggest that SIRT6 may be a potential therapeutic target for the treatment of obesity and associated metabolic disorders, such as liver disease.Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Instituto de Salud Carlos IIIEuropean Regional Development Fund (FEDER

Temperature but not leptin prevents semi-starvation induced hyperactivity in rats: implications for anorexia nervosa treatment

The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats. Alternatively, ambient temperature is a key modulating factor of activity in semi-starved rats. The aim of the study is to compare the efficacy of leptin with increased ambient temperature in the prevention of hyperactivity in semi-starved rats. 74 Sprague-Dawley male rats were employed in two experiments with the difference residing in the length of baseline. After an extended (28 days), or shorter (14 days) baseline with free access to food and the running wheel, housed at 21 degrees C, animals were either ad-lib feed or food restricted (60% of food ingested during previous week) and infused with same amount of leptin at 21 degrees C, 25 degrees C, or vehicle at 21 degrees C, 25 degrees C and 32 degrees C for a week. Animals housed at 32 degrees C significantly reduced wheel running and weight loss during food restriction while animals given leptin did not yield no differences in activity or weight loss. Moreover, unlike animals housed at 32 degrees C, body temperature of leptin infused animals housed at 21 degrees C was significantly reduced during food restriction. Furthermore, leptin treated rats without a preceding stable pattern of activity displayed a severe dysregulation of circadian rhythm in activity and a collapse of body temperature. Housing temperature plays a more critical role than leptin in the regulation of semi-starvation induced hyperactivity in rats, which may be of relevance for the management of hyperactivity in anorexia nervosa

Temperature but not leptin prevents semi-starvation induced hyperactivity in rats: implications for anorexia nervosa treatment

The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats. Alternatively, ambient temperature is a key modulating factor of activity in semi-starved rats. The aim of the study is to compare the efficacy of leptin with increased ambient temperature in the prevention of hyperactivity in semi-starved rats. 74 Sprague-Dawley male rats were employed in two experiments with the difference residing in the length of baseline. After an extended (28 days), or shorter (14 days) baseline with free access to food and the running wheel, housed at 21 °C, animals were either ad-lib feed or food restricted (60% of food ingested during previous week) and infused with same amount of leptin at 21 °C, 25 °C, or vehicle at 21 °C, 25 °C and 32 °C for a week. Animals housed at 32 °C significantly reduced wheel running and weight loss during food restriction while animals given leptin did not yield no differences in activity or weight loss. Moreover, unlike animals housed at 32 °C, body temperature of leptin infused animals housed at 21 °C was significantly reduced during food restriction. Furthermore, leptin treated rats without a preceding stable pattern of activity displayed a severe dysregulation of circadian rhythm in activity and a collapse of body temperature. Housing temperature plays a more critical role than leptin in the regulation of semi-starvation induced hyperactivity in rats, which may be of relevance for the management of hyperactivity in anorexia nervosaResearch leading to these results has received funding from the research budget from the Unidade Venres Clinicos (E.G., A.F.) and the Xunta de Galicia (ML: 2015-CP079 and 2016-PG068); Ministerio de Economía y Competitividad (MINECO) co-funded by the FEDER Program of EU (ML: RTI2018-101840-B-I00 and BFU2015-70454-REDT/Adipoplast) and Atresmedia Corporación (ML); MC, AGI, (CIBERobn), Xunta de Galicia and Instituto de Salud Carlos III (PI 17/01287). A.F. received a fellowship from Xunta de Galicia (Plan I2C-2014). The CiMUS is supported by the Xunta de Galicia (2016–2019, ED431G/05). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIIIS

ZNF577 Methylation Levels in Leukocytes From Women With Breast Cancer Is Modulated by Adiposity, Menopausal State, and the Mediterranean Diet

The methylation levels of ZNF577 in breast tumors has been previously identified as a possible epigenetic mark of breast cancer associated with obesity. The aim of the current study was to investigate differences in methylation levels of ZNF577 depending on obesity, menopausal state and dietary pattern in blood leukocytes, a non-invasive sample. The methylation levels of ZNF577 of two CpG sites (CpGs) located in promoter and island previously identified as differentially methylated according to adiposity and menopausal state by 450 k array (cg10635122, cg03562414) were evaluated by pyrosequencing in DNA from the blood leukocytes of breast cancer patients [n = 90; n = 64 (71.1%) overweight/obesity and n = 26 (28.9%) normal-weight] and paired tumor tissue biopsies (n = 8 breast cancer patients with obesity; n = 3/5 premenopausal/postmenopausal women). Differences in methylation levels were evaluated at each CpGs individually and at the mean of the two evaluated CpGs. Adherence to the Mediterranean diet was evaluated using the MEDAS-validated questionnaire, and the consumption of food groups of interest was also evaluated using the recommended intakes of the Sociedad Espanola de Nutricion Comunitaria. The methylation levels of ZNF577 were correlated between paired leukocytes and breast tumor biopsies (r = 0.62; p = 0.001). Moreover, higher methylation was found in leukocytes from patients with obesity (p = 0.002) and postmenopausal patients (p = 0.022) than patients with normal-weight or premenopausal, respectively. After adjusting for the body mass index and age, higher levels of ZNF577 methylation were also found in women with greater adherence to the Mediterranean diet (p = 0.017) or specific foods. Relevantly, the methylation levels of ZNF577 showed a good ability for fish consumption detection [area under the ROC curve (AUC) = 0.72; p = 0.016]. In conclusion, the association between methylation of ZNF577 and adiposity, menopausal state, and adherence to the Mediterranean diet can be detected in the blood leukocytes. The results guarantee the need of performing further studies in longer longitudinal cohorts in order to elucidate the role of ZNF577 methylation in the association between breast cancer, adiposity and dietary patterns

Epigenetic effects of healthy foods and lifestyle habits from the southern european atlantic diet pattern: a narrative review

Recent scientific evidence has shown the importance of diet and lifestyle habits for the proper functioning of the human body. A balanced and healthy diet, physical activity, and psychological well-being have a direct beneficial effect on health and can have a crucial role in the development and prognosis of certain diseases. The Southern European Atlantic diet, also named the Atlantic diet, is a unique dietary pattern that occurs in regions that present higher life expectancy, suggesting that this specific dietary pattern is associated with positive health effects. In fact, it is enriched with nutrients of high biological value, which, together with its cooking methods, physical activity promotion, reduction in carbon footprint, and promoting of family meals, promote these positive effects on health. The latest scientific advances in the field of nutri-epigenetics have revealed that epigenetic markers associated with food or nutrients and environmental factors modulate gene expression and, therefore, are involved with both health and disease. Thus, in this review, we evaluated the main aspects that define the Southern European Atlantic diet and the potential epigenetic changes associated with them based on recent studies regarding the main components of these dietary patterns. In conclusion, based on the information existing in the literature, we postulate that the Southern European Atlantic diet could promote healthy aging by means of epigenetic mechanisms. This review highlights the necessity of performing longitudinal studies to demonstrate this proposalS