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Pleiotrophin (PTN) is crucial for embryonic development and pancreas organogenesis as it regulates metainflammation, metabolic homeostasis, thermogenesis, and glucose tolerance. Pleiotrophin deletion is associated with a lipodystrophic phenotype in which adipose tissue plasticity is altered in late life. This study explored the impact of pleiotrophin deletion on pancreatic morphology and function in later life. We analyzed glucose tolerance and circulating parameters on female wild-type (Ptn+/+) and knock-out (Ptn−/−) mice. At 9 and 15 months, we conducted morphometric analyses of pancreatic islets and evaluated the levels of insulin, glucagon, somatostatin, glucose transporter 2 (GLUT2), vesicle-associated membrane protein 2 (VAMP2), and synaptosome-associated protein 25 (SNAP25) via immunofluorescence. The effect of PTN on glucose-stimulated insulin secretion (GSIS) was evaluated in INS1E cells and isolated islets. Ptn−/− mice showed hyperinsulinemia, impaired glucose tolerance, and increased homeostatic model assessment for insulin resistance (HOMA-IR) with age. While Ptn+/+ islets enlarge with age, in Ptn−/− mice, the median size decreased, and insulin content increased. Vesicle transport and exocytosis proteins were significantly increased in 9-month-old Ptn−/− islets. Islets from Ptn−/− mice showed impaired GSIS and decreased cell membrane localization of GLUT2 whereas, PTN increased GSIS in INS1E cells. Ptn deletion accelerated age-related changes in the endocrine pancreas, affecting islet number and size, and altering VAMP2 and SNAP25 levels and GLUT2 localization leading to impaired GSIS and insulin accumulation in islets. [ABSTRACT FROM AUTHOR]

Pregnancy is a physiological stress that requires dynamic, regulated changes affecting maternal and fetal adiposity. Excessive accumulation of dysfunctional adipose tissue defined by metabolic and molecular alterations cause severe health consequences for mother and fetus. When subjected to sustained overnutrition, the cellular and lipid composition of the adipose tissue changes predisposing to insulin resistance, diabetes, and other metabolic disorders compromising the outcome of the pregnancy. Moreover, excessive maternal weight gain, usually in the context of obesity, predisposes to an increased flux of nutrients from mother to fetus throughout the placenta. The fetus of an obese mother will accumulate more adiposity and may increase the risk of future metabolic disorder later in life. Thus, further understanding of the interaction between maternal metabolism, epigenetic regulation of the adipose tissue, and their transgenerational transfer are required to mitigate the adverse health outcomes for the mother and the fetus associated with maternal obesity., Author(s): Patricia Corrales [sup.1] , Antonio Vidal-Puig [sup.2] [sup.3] [sup.4] , Gema Medina-Gómez [sup.1] Author Affiliations: (1) Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, [...]

The aim of this work was to investigate the effect of the whole-body deletion of p27 on the activity of brown adipose tissue and the susceptibility to develop obesity and glucose homeostasis disturbances in mice, especially when subjected to a high fat diet. p27 knockout (p27−/−) and wild type (WT) mice were fed a normal chow diet or a high fat diet (HFD) for 10-weeks. Body weight and composition were assessed. Insulin and glucose tolerance tests and indirect calorimetry assays were performed. Histological analysis of interscapular BAT (iBAT) was carried out, and expression of key genes/proteins involved in BAT function were characterized by qPCR and Western blot. iBAT activity was estimated by 18F-fluorodeoxyglucose (18FDG) uptake with microPET. p27−/− mice were more prone to develop obesity and insulin resistance, exhibiting increased size of all fat depots. p27−/− mice displayed a higher respiratory exchange ratio. iBAT presented larger adipocytes in p27−/− HFD mice, accompanied by downregulation of both Glut1 and uncoupling protein 1 (UCP1) in parallel with defective insulin signalling. Moreover, p27−/− HFD mice exhibited impaired response to cold exposure, characterized by a reduced iBAT 18FDG uptake and difficulty to maintain body temperature when exposed to cold compared to WT HFD mice, suggesting reduced thermogenic capacity. These data suggest that p27 could play a role in BAT activation and in the susceptibility to develop obesity and insulin resistance. [ABSTRACT FROM AUTHOR]

Background Bariatric surgery (BS) has been postulated as the most effective measure for weight reduction. Weight loss improves metabolic parameters and exerts changes in renal function that lead to the amelioration of absolute or relative glomerular hyperfiltration, a condition that may be renoprotective in the long term. However, few studies have demonstrated the influence of BS in patients with severe obesity and chronic kidney disease (CKD). Our objective was to analyse the evolution of renal function, adipose tissue–derived molecules and inflammatory parameters in patients with CKD after BS. Methods This is an observational and prospective study. Thirty patients were screened and 12 were included between January 2016 and January 2018 with a 24-month follow-up. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Adipokines, cytokines, circulating hormones and fibrotic parameters were evaluated before and 12 months after BS using the Bioplex system. Results The mean age was 50.6 years and 58.3% were males. Seven patients had a body mass index >40 kg/m2 and 66.7% were diabetic. Twenty-four months following BS there was a significant decrease in body weight (36.4%). Proteinuria decreased by 63.7 ± 28.2%. Measured GFR significantly diminished from before surgery to Month 24 after surgery (94 ± 44 to 79 ± 44 mL/min, P = 0.03). There was a significant decrease in adipocyte-derived molecules (leptin and vifastin) as well as in pro-inflammatory cytokines [interleukin (IL)-1β, tumour necrosis factor α, IL-6 and monocyte chemoattractant protein-1] and other circulating factors (vascular endothelial growth factor and transforming growth factor β isoforms). Conclusions BS is an effective option to prevent kidney damage in obese subjects with CKD due to the improvement of glomerular hyperfiltration, adipocyte cytokines metabolic and inflammatory parameters. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to go deeper in the self-perception of weight and health status among the Spanish population, together with the connections of familiar relationships, physical activity practice, nutritional habits, and sleep patterns with the presence of obesity. Methods: A total of 1,000 subjects were enrolled in April 2017 in a representative adult Spanish population sample. Computer-assisted telephone interviewing was used and self-reported anthropometric data was obtained. Results: The population was composed of 51.3% women, with a mean age of 48 (36–63) years and a BMI of 23.2 (20.3–26.6). Although only 17.7% of subjects with self-reported obesity exhibited the self-perception to suffer from obesity, they referred a bad (16%) or regular (47%) self-perceived health status. Subjects who considered themselves as people with overweight and obesity displayed a BMI of 30.5 (28.7–32.2) and 37.1 (34.8–41.5), respectively. The obesity group displayed the highest percentage (71.9%) of participants with some first-degree relative with overweight or obesity (p < 0.001) in comparison with the other groups. The main reason put forward of preventing healthy eating among subjects with obesity was that they dislike healthy food. The multivariable logistic regression model for presence of obesity showed that there was a significant association with older age, presence of a first-degree relative with weight excess, a positive snacking habit, and daily alcohol consumption (p ≤ 0.019). Conclusion: The Spanish population has a low self-perception of obesity. Our data also reinforces the strong association between obesity and age, family interactions, usual snacking, and daily consumption of wine or beer. [ABSTRACT FROM AUTHOR]