Nuria Vilarrasa

Evaluation of Bone Mineral Density Loss in Morbidly Obese Women After Gastric Bypass: 3-Year Follow-Up

Studies that evaluate the influence of gastric bypass (RYGP) on bone mass are limited to short-term follow-up. We analysed changes in bone mineral density (BMD) three years after surgery and evaluated the main determinants of the development of bone disease. Prospective study of 59 morbidly obese white women aged 46 ± 8 years. BMD scanning using DEXA and plasma determinations of calcium, parathyroid hormone, 25-hydroxyvitamin D and insulin-like growth factor-I were made prior, at 12 months and 3 years after surgery. In the first postoperative year BMD decreased at femoral neck (FN) 10.2 % and in the lumbar spine (LS) 3.2 %, in the third year it additionally decreased 2.7 % and 3.1 %, respectively. BMD at both sites remained above the values of women of the same age. In the follow-up, 1.7 % developed osteoporosis at FN and 6.8 % at LS. Patients with bone disease were older, the percentage of women with menopause was greater in this group and had lower initial and final values of lean mass. The percentage of BMD loss at FN remained positively associated with the percentage of lean mass loss [β 0.304, p = 0.045], and menopause [β 0.337, p = 0.025]. Major osteoporotic fracture and hip fracture risk was low even in menopausal patients (3.1 % and 0.40 %, respectively). After RYGP menopausal women and those with greater lean mass loss are at higher risk of BMD loss but progression to osteoporosis is uncommon and the risk of fracture is low.

Distribution and determinants of adiponectin, resistin and ghrelin in a randomly selected healthy population

Objective  Adiponectin, resistin, ghrelin and the IGF‐I system seem to play an important role in the regulation of body composition throughout life, but the mechanisms are not well understood. The aim of our study was to analyse the distribution among sexes and all decades of the adult life of adiponectin, resistin and ghrelin and their relationship with anthropometric, body composition parameters and the IGF‐I system.

Lifetime obesity in patients with eating disorders: increasing prevalence, clinical and personality correlates

Objectives : The aims of our study were to examine the lifetime prevalence of obesity rate in eating disorders (ED) subtypes and to examine whether there have been temporal changes among the last 10 years and to explore clinical differences between ED with and without lifetime obesity. Methods : Participants were 1383 ED female patients (DSM-IV criteria) consecutively admitted, between 2001 and 2010, to Bellvitge University Hospital. They were assessed by means of the Eating Disorders Inventory-2, the Symptom Checklist-90—Revised, the Bulimic Investigatory Test Edinburgh and the Temperament and Character Inventory—Revised. Results : The prevalence of lifetime obesity in ED cases was 28.8% (ranging from 5% in anorexia nervosa to 87% in binge-eating disorders). Over the last 10 years, there has been a threefold increase in lifetime obesity in ED patients (p < .001). People with an ED and obesity had higher levels of childhood and family obesity (p < .001), a later age of onset and longer ED duration; and had higher levels of eating, general and personality symptomatology. Conclusions : Over the last 10 years, the prevalence of obesity associated with disorders characterized by the presence of binge episodes, namely bulimic disorders, is increasing, and this is linked with greater clinical severity and a poorer prognosis. Copyright

Effect of weight loss induced by gastric bypass on proinflammatory interleukin‐18, soluble tumour necrosis factor‐α receptors, C‐reactive protein and adiponectin in morbidly obese patients

Objective  Interleukin‐18 (IL‐18) is a potent proinflammatory cytokine whose role in human obesity has recently been suggested. The aim of our study was to analyse in morbidly obese patients undergoing gastric bypass, the relationship of IL‐18 with insulin resistance and with proinflammatory cytokines (tumour necrosis factor‐α receptors, sTNFR), C‐reactive protein (CRP) and with adiponectin.

Lifetime obesity in patients with eating disorders

Objectives : The aims of our study were to examine the lifetime prevalence of obesity rate in eating disorders (ED) subtypes and to examine whether there have been temporal changes among the last 10 years and to explore clinical differences between ED with and without lifetime obesity. Methods : Participants were 1383 ED female patients (DSM-IV criteria) consecutively admitted, between 2001 and 2010, to Bellvitge University Hospital. They were assessed by means of the Eating Disorders Inventory-2, the Symptom Checklist-90—Revised, the Bulimic Investigatory Test Edinburgh and the Temperament and Character Inventory—Revised. Results : The prevalence of lifetime obesity in ED cases was 28.8% (ranging from 5% in anorexia nervosa to 87% in binge-eating disorders). Over the last 10 years, there has been a threefold increase in lifetime obesity in ED patients (p < .001). People with an ED and obesity had higher levels of childhood and family obesity (p < .001), a later age of onset and longer ED duration; and had higher levels of eating, general and personality symptomatology. Conclusions : Over the last 10 years, the prevalence of obesity associated with disorders characterized by the presence of binge episodes, namely bulimic disorders, is increasing, and this is linked with greater clinical severity and a poorer prognosis. Copyright

A nontargeted proteomic approach to the study of visceral and subcutaneous adipose tissue in human obesity

Subcutaneous (SAT) and visceral adipose tissue (VAT) differ in biochemical and metabolic properties, especially when obesity is present. We submitted paired SAT and VAT samples from six morbidly obese patients and six non-obese persons to two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight mass spectrometry. Compared with non-obese subjects, obese patients presented with increased carboxylesterase-1, zinc finger protein 324A, annexin A5, ubiquitin carboxyl-terminal hydrolase, α-crystallin B chain, osteoglycin, retinal dehydrogenase-1 and 14-3-3 protein γ, and decreased transferrin, complement C3, fibrinogen γ chain, albumin, α1-antitrypsin and peroxiredoxin-6, irrespective of the adipose tissue depot studied. SAT and VAT differed in protein species of fibrinogen and osteoglycin, whereas adipose tissue depot and obesity interacted on the protein abundance of actin, α-actinin 1, one protein species of carboxylesterase-1, retinal dehydrogenase-1 and 14-3-3 protein γ. Our nontargeted proteomic approach identified novel protein species that may be involved in the development of obesity in humans.

Monocyte chemoattractant protein-1 in obesity and type 2 diabetes. Insulin sensitivity study.

Objective: Our goal was to test any association between human plasma circulating levels of monocyte chemoattractant protein‐1 (cMCP‐1) and insulin resistance and to compare monocyte chemoattractant protein‐1 (MCP‐1) adipose tissue gene expression and cMCP‐1 in relation with inflammatory markers.

Disruption of GIP/GIPR Axis in Human Adipose Tissue Is Linked to Obesity and Insulin Resistance

CONTEXT Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. OBJECTIVE Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. DESIGN GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. RESULTS GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. CONCLUSIONS GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.

Paired Subcutaneous and Visceral Adipose Tissue Aquaporin-7 Expression in Human Obesity and Type 2 Diabetes: Differences and Similarities between Depots

CONTEXT AQP7 is considered to be the sole adipose glycerol channel, and its regulation is crucial for glycemia control. OBJECTIVES In this work, we aimed to further characterize AQP7 in human adipose tissue in obesity and type 2 diabetes (T2D): 1) to assess AQP7 expression levels in paired abdominal adipose tissue depots (sc and visceral); 2) to relate it with gene expression of genes involved in lipid metabolism; and 3) to confirm that AQP7 is mainly expressed in the adipocytes. DESIGN We conducted a transversal study of gene expression in paired samples of sc adipose tissue (SAT) and visceral adipose tissue (VAT). PATIENTS Caucasian lean and obese subjects (n = 62, matched for age and gender) and T2D subjects (n = 11, matched for age, gender, and BMI with their control group) participated in the study. MAIN OUTCOME MEASURE We measured AQP7 expression levels in paired SAT and VAT. RESULTS We have proved the presence of AQP7 mRNA and protein in the adipocyte rather than the stromovascular fraction of adipose tissue (P = 0.001) and in mature adipocytes when differentiated in vitro. Increased AQP7 mRNA expression levels in VAT from T2D obese subjects (P < 0.05) were found. AQP7 transcript levels ratio of SAT vs. VAT changed with the presence of obesity and T2D. Interestingly, there were positive associations between AQP7 and both lipogenic and lipolytic genes in a similar manner in both adipose depots. CONCLUSIONS Taken together, these data suggest a subtle regulation between adipose depots of the sole adipose aquaporin, AQP7, which is unbalanced in obesity and T2D.

Human serum levels of fetal antigen 1 (FA1/Dlk1) increase with obesity, are negatively associated with insulin sensitivity and modulate inflammation in vitro.

Objective:To investigate fetal antigen 1 (FA1) protein within the context of human obesity and its relation with insulin sensitivity.Subjects:Cross-sectional study that analyses circulating levels of FA1 in two selected human cohorts: n=127 men for the study of FA1 circulating levels in the context of obesity and insulin sensitivity (Si); and n=61 severely obese women before and after bariatric surgery. The response in vitro to FA1 protein on human cell lines of monocytes, preadipocytes and mature adipocytes was studied.Measurements:Anthropometrical parameters: body mass index, waist-to-hip ratio, waist circumference, fat-free mass and fat mass. Clinical parameters: lipid profile (high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides), glycemic profile (fasting glucose, insulin, Si, HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), cytokines (sIL-6), adipokines (adiponectin) and circulating soluble fractions of tumor necrosis factor-α receptors 1 and 2 (sTNFR1 and sTNFR2).Results:In the obesity study, levels of FA1 in serum were found to increase with obesity. The Si index was negatively dependent on FA1 levels. In severe obesity, serum levels of FA1 decreased 1.4-fold 6 months after bariatric surgery. In vitro assays with FA1 protein on human monocytes and adipocytes cell lines modified the expression of pro-inflammatory cytokines and adipokines (tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), IL-6 (interleukin-6) and adiponectin).Conclusion:FA1 serum levels were increased in obese subjects and might influence Si. The stimulatory effect of FA1 protein on pro-inflammatory cytokines on both immune and adipose cell types could contribute to worsening the inflammatory environment observed in obesity.