56 research outputs found

    Lack of Hypophagia in CB1 Null Mice is Associated to Decreased Hypothalamic POMC and CART Expression

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    Background: Cumulative data indicate that the endocannabinoid system plays a major role in feeding behavior and energy balance. Genetic silencing of cannabinoid receptor type 1 (CB1) reduces body weight gain, independently of food intake. Methods: In this work, we investigated whether the hypothalamic neuropeptide expression pattern supports the absence of the anorexigenic response observed under constitutive CB1 ablation, by using neuronal CB1 conditional null mice (CamK-CB1-KO) and whole body CB1 null mice (CB1-KO). Results: Our data showed that both CB1 null models display a marked decrease in proopiomelanocortin (POMC) and cocaine-amphetamine-regulated transcript (CART) expression in the arcuate nucleus of the hypothalamus (ARC). Conclusions: This evidence suggests that a lack of hypophagia is associated with the suppression of ARC anorexigenic neuropeptides and that behavioral changes in food intake (or lack thereof) after constitutive CB1 ablation are likely mediated by impaired melanocortin and CART signaling in the hypothalamus.The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement nº 281854 of the ObERStress European Research Council Project (Dr López) and 245009 of the Neurofast project (Drs Nogueiras, Diéguez, and López); Xunta de Galicia (Dr Nogueiras: EM 2012/039 and 2012-CP069; Dr López: 2012-CP070); the Frank Mohn Foundation, Bergen (Dr Fernø); Instituto de Salud Carlos III (ISCIII; Dr López: PI12/01814 and PIE13/00024); and MINECO, co-funded by the FEDER Program of EU (Dr Nogueiras: RyC-2008-02219 and BFU2012-35255; Dr Diéguez: BFU2011-29102). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIIIS

    Phonological fluency norms for Spanish middle-aged and older adults provided by the SCAND initiative (P, M, & R)

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    Objective: Verbal fluency tests are quick and easy to administer neuropsychological measures and are regularly used in neuropsychological assessment. Additionally, phonological fluency is a widely used paradigm that is sensitive to cognitive impairment. This paper offers normative data of phonological verbal fluency (letters P, M, R) for Spanish middle- and older-aged adults, considering sociodemographic factors, and different measures such as the total number of words, errors (perseveration and intrusions), and 15 sec-segmented scores. Method: A total of 1165 cognitively unimpaired participants aged between 50 and 89 years old, participated in the study. Data for P were obtained for all participants. Letters M and R were also administered to a subsample of participants (852) aged 60 to 89 years. In addition, errors and words produced every 15 seconds were collected in the subsample. To verify the effect of sociodemographic variables, linear regression was used. Adjustments were calculated for variables that explained at least 5% of the variance (R2 ≥ .05). Results: Means and standard deviations by age, scaled scores, and percentiles for all tests across different measures are shown. No determination coefficients equal to or greater than .05 were found for sex or age. The need to establish adjustments for the educational level was only found in some of the measures. Conclusions: The current norms provide clinically useful data to evaluate Spanish-speaking natives from Spain aged from 50 to 89 years. Specific patterns of cognitive impairment can be analyzed using these normative data and may be important in neuropsychological assessmentObjective: Verbal fluency tests are quick and easy to administer neuropsychological measures and are regularly used in neuropsychological assessment. Additionally, phonological fluency is a widely used paradigm that is sensitive to cognitive impairment. This paper offers normative data of phonological verbal fluency (letters P, M, R) for Spanish middle- and older-aged adults, considering sociodemographic factors, and different measures such as the total number of words, errors (perseveration and intrusions), and 15 sec-segmented scores. Method: A total of 1165 cognitively unimpaired participants aged between 50 and 89 years old, participated in the study. Data for P were obtained for all participants. Letters M and R were also administered to a subsample of participants (852) aged 60 to 89 years. In addition, errors and words produced every 15 seconds were collected in the subsample. To verify the effect of sociodemographic variables, linear regression was used. Adjustments were calculated for variables that explained at least 5% of the variance (R2 ≥ .05). Results: Means and standard deviations by age, scaled scores, and percentiles for all tests across different measures are shown. No determination coefficients equal to or greater than .05 were found for sex or age. The need to establish adjustments for the educational level was only found in some of the measures. Conclusions: The current norms provide clinically useful data to evaluate Spanish-speaking natives from Spain aged from 50 to 89 years. Specific patterns of cognitive impairment can be analyzed using these normative data and may be important in neuropsychological assessmentS

    Gut Microbiota Composition in Male Rat Models under Different Nutritional Status and Physical Activity and Its Association with Serum Leptin and Ghrelin Levels

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    Background: Several evidences indicate that gut microbiota is involved in the control of host energy metabolism. Objective: To evaluate the differences in the composition of gut microbiota in rat models under different nutritional status and physical activity and to identify their associations with serum leptin and ghrelin levels. Methods: In a case control study, forty male rats were randomly assigned to one of these four experimental groups: ABA group with food restriction and free access to exercise; control ABA group with food restriction and no access to exercise; exercise group with free access to exercise and feed ad libitum and ad libitum group without access to exercise and feed ad libitum. The fecal bacteria composition was investigated by PCR-denaturing gradient gel electrophoresis and real-time qPCR. Results: In restricted eaters, we have found a significant increase in the number of Proteobacteria, Bacteroides, Clostridium, Enterococcus, Prevotella and M. smithii and a significant decrease in the quantities of Actinobacteria, Firmicutes, Bacteroidetes, B. coccoides-E. rectale group, Lactobacillus and Bifidobacterium with respect to unrestricted eaters. Moreover, a significant increase in the number of Lactobacillus, Bifidobacterium and B. coccoides-E. rectale group was observed in exercise group with respect to the rest of groups. We also found a significant positive correlation between the quantity of Bifidobacterium and Lactobacillus and serum leptin levels, and a significant and negative correlation among the number of Clostridium, Bacteroides and Prevotella and serum leptin levels in all experimental groups. Furthermore, serum ghrelin levels were negatively correlated with the quantity of Bifidobacterium, Lactobacillus and B. coccoides-Eubacterium rectale group and positively correlated with the number of Bacteroides and Prevotella. Conclusions: Nutritional status and physical activity alter gut microbiota composition affecting the diversity and similarity. This study highlights the associations between gut microbiota and appetite-regulating hormones that may be important in terms of satiety and host metabolism

    Adiponectin accounts for gender differences in hepatocellular carcinoma incidence

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    Hepatocellular carcinoma (HCC) is the sixth most common cancer type and the fourth leading cause of cancer-related death. This cancer appears with higher incidence in men and during obesity; however, the specific mechanisms underlying this correlation are unknown. Adipose tissue, a key organ in metabolic syndrome, shows evident gender disparities in the production of adipokines. Levels of the important adipokine adiponectin decrease in men during puberty, as well as in the obese state. Here, we show that this decrease in adiponectin levels is responsible for the increased liver cancer risk in males. We found that testosterone activates the protein JNK in mouse and human adipocytes. JNK-mediated inhibition of adiponectin secretion increases liver cancer cell proliferation, since adiponectin protects against liver cancer development through the activation of AMP-activated protein kinase (AMPK) and p38α. This study provides insight into adipose tissue to liver crosstalk and its gender relation during cancer development, having the potential to guide strategies for new cancer therapeutics.G. Sabio is an investigator on the Ramón y Cajal Program. E. Manieri is a La Caixa Foundation fellow. L. Herrera-Melle is a fellow of the Ministerio de Educación, Cultura y Deporte (FPU15-05802). This study was funded by the following grants: G. Sabio was funded by the European Research Council (ERC 260464), European Foundation for the Study of Diabetes–Lilly, Ministerio de Ciencia, Innovación y Universidades (MICINN/SAF2016-79126-R), Comunidad de Madrid (B2017/BMD-3733), and BBVA Becas Leonardo a Investigadores y Creadores Culturales (Investigadores-BBVA-2017; IN[17]_BBM_BAS_0066); M. Marcos was funded by Instituto de Salud Carlos III and Federación Española de Enfermedades Raras (PI16/01548); and J.L. Torres was funded by Junta de Castilla y León GRS (1587/A/17). F.J. Cubero is a Ramón y Cajal Researcher (RYC-2014-15242) and a Gilead Liver Research Scholar 2018, and his work is supported by the Ministerio de Economia y Competitividad Retos (SAF2016-78711), Comunidad de Madrid (S2017/BMD-3727), The Alan Morement Memorial Fund Cholangiocarcinoma Charity (2018/117), the European Cooperation in Science and Technology Action (CA17112), and the European Foundation for Alcohol Research (EA14/18). L. Moran is a Comunidad de Madrid fellow (S2017/BMD-3727). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

    Nesfatin-1 in human and murine cardiomyocytes: synthesis, secretion, and mobilization of GLUT-4

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    Nesfatin-1, a satiety-inducing peptide identified in hypothalamic regions that regulate energy balance, is an integral regulator of energy homeostasis and a putative glucose-dependent insulin coadjuvant. We investigated its production by human cardiomyocytes and its effects on glucose uptake, in the main cardiac glucose transporter GLUT-4 and in intracellular signaling. Quantitative RT-PCR, Western blots, confocal immunofluorescence microscopy, and ELISA of human and murine cardiomyocytes and/or cardiac tissue showed that cardiomyocytes can synthesize and secrete nesfatin-1. Confocal microscopy of cultured cardiomyocytes after GLUT-4 labeling showed that nesfatin-1 mobilizes this glucose transporter to cell peripherals. The rate of 2-deoxy-D-[(3)H]glucose incorporation demonstrated that nesfatin-1 induces glucose uptake by HL-1 cells and cultured cardiomyocytes. Nesfatin-1 induced dose- and time-dependent increases in the phosphorylation of ERK1/2, AKT, and AS160. In murine and human cardiac tissue, nesfatin-1 levels varied with diet and coronary health. In conclusion, human and murine cardiomyocytes can synthesize and secrete nesfatin-1, which is able to induce glucose uptake and the mobilization of the glucose transporter GLUT-4 in these cells. Nesfatin-1 cardiac levels are regulated by diet and coronary health
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