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Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue.

Our objectives were to study the association between epidural analgesia and risk of severe perineal laceration (SPL), and identify additional risk factors for SPL. This multicentre study consisted of an analysis of data from the MidconBirth Phase I Database, on the use of EA and perineal results during childbirth. (World Health Organization, International Clinical Trials Registry Platform, 2016: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN17833269). We conducted a prospective study of pregnant women at term between July 2016 and July 2017 in 30 public maternity hospitals in Catalonia, Spain. Inclusion criteria were an uncomplicated singleton pregnancy, in cephalic presentation and vaginal birth. Data was analysed separately for instrumental births and spontaneous vaginal births, as the former is more frequently associated with episiotomy and more perineal lacerations. Risk factors as well as protective factors in each cohort of women (instrumental and spontaneous vaginal birth), were identified. Multivariate logistic regression model was performed to study the association between epidural analgesia and SPL to identify potential confounders. Odds ratios (OR), using 95% confidence intervals (CI) were constructed. During the study period, 5497 eligible women gave birth, 77.46% of them received epidural analgesia. SPL occurred in 1.63% of births. The univariate analysis showed births with epidural analgesia had significantly higher rates of inductions, augmentation of labour, lithotomy position for birth and episiotomy. However, this association disappeared when the variable "type of vaginal birth" was introduced. In multivariate logistic regression, nulliparity was the major predictor for SPL (OR: 0.17; CI 95%: 0.08-0.34, p: 0.000). Epidural analgesia was not associated with SPL once confounding factors were included. Other interesting factors associated with SPL were identified. This paper identifies important practice areas which contribute to SPL and w

A functional population of adipocyte precursors, termed adipose-derived stromal/stem cells (ASCs), is crucial for proper adipose tissue (AT) expansion, lipid handling, and prevention of lipotoxicity in response to chronic positive energy balance. We previously showed that obese human subjects contain a dysfunctional pool of ASCs. Elucidation of the mechanisms underlying abnormal ASC function might lead to therapeutic interventions for prevention of lipotoxicity by improving the adipogenic capacity of ASCs.Using epigenome-wide association studies, we explored the impact of obesity on the methylation signature of human ASCs and their differentiated counterparts. Mitochondrial phenotyping of lean and obese ASCs was performed. TBX15 loss- and gain-of-function experiments were carried out and western blotting and electron microscopy studies of mitochondria were performed in white AT biopsies from lean and obese individuals.We found that DNA methylation in adipocyte precursors is significantly modified by the obese environment, and adipogenesis, inflammation, and immunosuppression were the most affected pathways. Also, we identified TBX15 as one of the most differentially hypomethylated genes in obese ASCs, and genetic experiments revealed that TBX15 is a regulator of mitochondrial mass in obese adipocytes. Accordingly, morphological analysis of AT from obese subjects showed an alteration of the mitochondrial network, with changes in mitochondrial shape and number.We identified a DNA methylation signature in adipocyte precursors associated with obesity, which has a significant impact on the metabolic phenotype of mature adipocytes.

Objective: Glycogen metabolism has emerged as a mediator in the control of energy homeostasis and studies in murine models reveal that adipose tissue might contain glycogen stores. Here we investigated the physio(patho)logical role of glycogen in human adipose tissue in the context of obesity and insulin resistance. Methods: We studied glucose metabolic flux of hypoxic human adipoctyes by nuclear magnetic resonance and mass spectrometry-based metabolic approaches. Glycogen synthesis and glycogen content in response to hypoxia was analyzed in human adipocytes and macrophages. To explore the metabolic effects of enforced glycogen deposition in adipocytes and macrophages, we overexpressed PTG, the only glycogen-associated regulatory subunit (PP1-GTS) reported in murine adipocytes. Adipose tissue gene expression analysis was performed on wild type and homozygous PTG KO male mice. Finally, glycogen metabolism gene expression and glycogen accumulation was analyzed in adipose tissue, mature adipocytes and resident macrophages from lean and obese subjects with different degrees of insulin resistance in 2 independent cohorts. Results: We show that hypoxia modulates glucose metabolic flux in human adipocytes and macrophages and promotes glycogenesis. Enforced glycogen deposition by overexpression of PTG re-orients adipocyte secretion to a pro-inflammatory response linked to insulin resistance and monocyte/lymphocyte migration. Furthermore, glycogen accumulation is associated with inhibition of mTORC1 signaling and increased basal autophagy flux, correlating with greater leptin release in glycogen-loaded adipocytes. PTG-KO mice have reduced expression of key inflammatory genes in adipose tissue and PTG overexpression in M0 macrophages induces a pro-inflammatory and glycolytic M1 p

© AlphaMed Press 2016. Adipose tissue is a major source ofmesenchymal stemcells (MSCs), which possess a variety of properties that make them ideal candidates for regenerative and immunomodulatory therapies. Here, we compared the immunophenotypic profile of human adipose-derived stem cells (hASCs) from lean and obese individuals, and explored its relationship with the apparent altered plasticity of hASCs.Wealso hypothesized that persistent hypoxia treatment of cultured hASCsmay be necessary but not sufficient to drive significant changes inmature adipocytes. hASCswere obtained fromsubcutaneous adipose tissue of healthy, adult, female donors undergoing abdominal plastic surgery: lean (n = 8; bodymass index [BMI]: 23 ± kg/m2) and obese (n = 8; BMI: 35 ± kg/m2). Cell surface marker expression, proliferation and migration capacity, and adipogenic differentiation potential of cultured hASCs at two different oxygen conditions were studied. Compared with lean-derived hASCs, obese-derived hASCs demonstrated increased proliferation and migration capacity but decreased lipid droplet accumulation, correlating with a higher expression of human leukocyte antigen (HLA)-II and cluster of differentiation (CD) 106 and lower expression of CD29. Of interest, adipogenic differentiation modified CD106, CD49b, HLA-ABC surface protein expression, which was dependent on the donor’s BMI. Additionally, low oxygen tension increased proliferation and migration of lean but not obese hASCs, which correlated with an altered CD36 and CD49b immunophenotypic profile. In summary, the differences observed in proliferation, migration, and differentiation capacity in obese hASCs occurred in parallel with changes in cell surfacemarkers, both under basal conditions and during differentiation. Therefore, obesit

Bariatric surgery is an operation on the stomach and/or intestines that helps patients with extreme obesity to lose weight. Even if bariatric surgery, compared with traditional obesity treatment, is more effective in reducing BMI, this approach does not achieve equal results in every patient. More, following bariatric surgery common problems are body image dissatisfaction and body disparagement: there is a significant difference between the weight loss clinicians consider successful (50% of excess weight) and the weight loss potential patients expect to achieve (at least 67% of the excess weight). The paper discusses the possible role of virtual reality (VR) in addressing this problem within an integrated treatment approach. More, the clinical case of a female bariatric patient who experienced body dissatisfaction even after a 30% body weight loss and a 62% excess body weight loss, is presented and discussed.