Weight loss-induced stress in subcutaneous adipose tissue is related to weight regain

Initial successful weight loss is often followed by weight regain after the dietary intervention. Compared with lean people, cellular stress in adipose tissue is increased in obese subjects. However, the relation between cellular stress and the risk for weight regain after weight loss is unclear. Therefore, we determined the expression levels of stress proteins during weight loss and weight maintenance in relation to weight regain. In vivo findings were compared with results from in vitro cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. In total, eighteen healthy subjects underwent an 8-week diet programme with a 10-month follow-up. Participants were categorised as weight maintainers or weight regainers (WR) depending on their weight changes during the intervention. Abdominal subcutaneous adipose tissue biopsies were obtained before and after the diet and after the follow-up. In vitro differentiated SGBS adipocytes were starved for 96 h with low (0.55 mm) glucose. Levels of stress proteins were determined by Western blotting. WR showed increased expressions of beta-actin, calnexin, heat shock protein (HSP) 27, HSP60 and HSP70. Changes of beta-actin, HSP27 and HSP70 are linked to HSP60, a proposed key factor in weight regain after weight loss. SGBS adipocytes showed increased levels of beta-actin and HSP60 after 96 h of glucose restriction. The increased level of cellular stress proteins in the adipose tissue of WR probably resides in the adipocytes as shown by in vitro experiments. Cellular stress accumulated in adipose tissue during weight loss may be a risk factor for weight regain

Validation, optimisation, and application data in support of the development of a targeted selected ion monitoring assay for degraded cardiac troponin T

AbstractCardiac troponin T (cTnT) fragmentation in human serum was investigated using a newly developed targeted selected ion monitoring assay, as described in the accompanying article: “Development of a targeted selected ion monitoring assay for the elucidation of protease induced structural changes in cardiac troponin T” [1]. This article presents data describing aspects of the validation and optimisation of this assay. The data consists of several figures, an excel file containing the results of a sequence identity search, and a description of the raw mass spectrometry (MS) data files, deposited in the ProteomeXchange repository with id PRIDE: PXD003187

A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data

Given the association of disturbances in non-esterified fatty acid (NEFA) metabolism with the development of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, computational models of glucose-insulin dynamics have been extended to account for the interplay with NEFA. In this study, we use arteriovenous measurement across the subcutaneous adipose tissue during a mixed meal challenge test to evaluate the performance and underlying assumptions of three existing models of adipose tissue metabolism and construct a new, refined model of adipose tissue metabolism. Our model introduces new terms, explicitly accounting for the conversion of glucose to glyceraldehye-3-phosphate, the postprandial influx of glycerol into the adipose tissue, and several physiologically relevant delays in insulin signalling in order to better describe the measured adipose tissues fluxes. We then applied our refined model to human adipose tissue flux data collected before and after a diet intervention as part of the Yoyo study, to quantify the effects of caloric restriction on postprandial adipose tissue metabolism. Significant increases were observed in the model parameters describing the rate of uptake and release of both glycerol and NEFA. Additionally, decreases in the model’s delay in insulin signalling parameters indicates there is an improvement in adipose tissue insulin sensitivity following caloric restriction.</p

Obesity-induced and weight-loss-induced physiological factors affecting weight regain

Weight regain after successful weight loss resulting from lifestyle interventions is a major challenge in the management of overweight and obesity. Knowledge of the causal mechanisms for weight regain can help researchers and clinicians to find effective strategies to tackle weight regain and reduce obesity-associated metabolic and cardiovascular complications. This Review summarizes the current understanding of a number of potential physiological mechanisms underlying weight regain after weight loss, including: the role of adipose tissue immune cells; hormonal and neuronal factors affecting hunger, satiety and reward; resting energy expenditure and adaptive thermogenesis; and lipid metabolism (lipolysis and lipid oxidation). We describe and discuss obesity-associated changes in these mechanisms, their persistence during weight loss and weight regain and their association with weight regain. Interventions to prevent or limit weight regain based on these factors, such as diet, exercise, pharmacotherapy and biomedical strategies, and current knowledge on the effectiveness of these interventions are also reviewed

A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss

Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietary intervention (DI). When people are following a diet, the volume of an adipocyte decreases by loss of triglycerides, which creates stress between the cell contents and the surrounding extracellular matrix (ECM). Previously, we observed that genetic variations in ECM genes are associated with an increased risk of weight regain. Objective: We investigated the relation between the expression of ECM genes during WL and a period of weight stabilization (WS) and the risk of weight regain. Design: In this randomized controlled trial, 61 healthy overweight or obese participants followed either a 5-wk very-low-calorie diet (VLCD; 500 kcal/d) or a 12-wk low-calorie diet (1250 kcal/d) (WL period) with a subsequent 4-wk WS period and a 9-mo follow-up. The WL and WS periods combined were considered the DI. Abdominal subcutaneous adipose tissue biopsy samples were collected for microarray analysis. Gene expression changes for a broad set of ECM-related genes were correlated with the weight-regain percentage (WR%). Results: A total of 26 of the 277 genes were significantly correlated with WR% during WL, WS, or the DI periods. Most correlations were observed in the VLCD group during the WS period. Four genes code for leukocyte-specific receptors. These and other genes belong to a group of 26 genes, among which the expression changes were highly correlated (r ≥ 0.7, P ≤ 0.001). This group could be divided into 3 subclusters linking to 2 biological processes-leukocyte integrin gene activity and ECM remodeling-and a link to insulin sensitivity was also apparent. Conclusions: Our present findings indicate the importance of adipose tissue leukocytes for the risk of weight regain. ECM modification also seems to be involved, and we observed a link to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT01559415.</p

A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss

Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietary intervention (DI). When people are following a diet, the volume of an adipocyte decreases by loss of triglycerides, which creates stress between the cell contents and the surrounding extracellular matrix (ECM). Previously, we observed that genetic variations in ECM genes are associated with an increased risk of weight regain. Objective: We investigated the relation between the expression of ECM genes during WL and a period of weight stabilization (WS) and the risk of weight regain. Design: In this randomized controlled trial, 61 healthy overweight or obese participants followed either a 5-wk very-low-calorie diet (VLCD; 500 kcal/d) or a 12-wk low-calorie diet (1250 kcal/d) (WL period) with a subsequent 4-wk WS period and a 9-mo follow-up. The WL and WS periods combined were considered the DI. Abdominal subcutaneous adipose tissue biopsy samples were collected for microarray analysis. Gene expression changes for a broad set of ECM-related genes were correlated with the weight-regain percentage (WR%). Results: A total of 26 of the 277 genes were significantly correlated with WR% during WL, WS, or the DI periods. Most correlations were observed in the VLCD group during the WS period. Four genes code for leukocyte-specific receptors. These and other genes belong to a group of 26 genes, among which the expression changes were highly correlated (r ≥ 0.7, P ≤ 0.001). This group could be divided into 3 subclusters linking to 2 biological processes-leukocyte integrin gene activity and ECM remodeling-and a link to insulin sensitivity was also apparent. Conclusions: Our present findings indicate the importance of adipose tissue leukocytes for the risk of weight regain. ECM modification also seems to be involved, and we observed a link to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT01559415.</p

Integrated visualization of a multi-omics study of starvation in mouse intestine

Our understanding of complex biological processes can be enhanced by combining different kinds of high-throughput experimental data, but the use of incompatible identifiers makes data integration a challenge. We aimed to improve methods for integrating and visualizing different types of omics data. To validate these methods, we applied them to two previous studies on starvation in mice, one using proteomics and the other using transcriptomics technology. We extended the PathVisio software with new plugins to link proteins, transcripts and pathways. A low overall correlation between proteome and transcriptome data was detected (Spearman rank correlation: 0.21). At the level of individual genes, correlation was highly variable. Many mRNA/protein pairs, such as fructose biphosphate aldolase B and ATP Synthase, show good correlation. For other pairs, such as ferritin and elongation factor 2, an interesting effect is observed, where mRNA and protein levels change in opposite directions, suggesting they are not primarily regulated at the transcriptional level. We used pathway diagrams to visualize the integrated datasets and found it encouraging that transcriptomics and proteomics data supported each other at the pathway level. Visualization of the integrated dataset on pathways led to new observations on gene-regulation in the response of the gut to starvation. Our methods are generic and can be applied to any multi-omics study. The PathVisio software can be obtained at http://www.pathvisio.org. Supplemental data are available at http://www.bigcat.unimaas.nl/data/jib-supplemental/, including instructions on reproducing the pathway visualizations of this manuscript

Adipose tissue meal-derived fatty acid uptake before and after diet-induced weight loss in adults with overweight and obesity

Objective: This study investigated whether diet-induced weight loss alters indices of in vivo postprandial fat uptake in adipose tissue (AT) and whether these changes are associated with weight regain in adults with overweight and obesity. Methods: In this randomized controlled trial, 16 (6 male) individuals (BMI: 28-35 kg/m2) were randomized to either a low-calorie diet (1,250 kcal/d) for 12 weeks or a very-low-calorie diet (500 kcal/d) for 5 weeks (weight loss [WL] period) followed by a 4-week weight-stable (WS) period (together, the dietary intervention [DI] period) and a 9-month follow-up period. Arteriovenous difference measurements combined with stable isotope labeling ([U-13C] palmitate) of a mixed meal were used to determine postprandial fatty acid uptake in AT. Results: Body weight was significantly reduced during the WL period (-8.2±0.6 kg, P<0.001), remained stable during the WS period (0.4±0.3 kg, P=0.150), and increased during follow-up (3.5±0.8 kg, P=0.001). Meal-derived in vivo fatty acid uptake dynamics across AT and expression of genes important for fatty acid uptake, storage, and release were not significantly changed during the DI period. Conclusions: Subcutaneous AT does not appear prone to enhanced meal-derived fatty acid uptake after weight loss, nor were fatty acid uptake dynamics detected as related to weight regain

Adipose tissue meal-derived fatty acid uptake before and after diet-induced weight loss in adults with overweight and obesity

Objective: This study investigated whether diet-induced weight loss alters indices of in vivo postprandial fat uptake in adipose tissue (AT) and whether these changes are associated with weight regain in adults with overweight and obesity. Methods: In this randomized controlled trial, 16 (6 male) individuals (BMI: 28-35 kg/m2) were randomized to either a low-calorie diet (1,250 kcal/d) for 12 weeks or a very-low-calorie diet (500 kcal/d) for 5 weeks (weight loss [WL] period) followed by a 4-week weight-stable (WS) period (together, the dietary intervention [DI] period) and a 9-month follow-up period. Arteriovenous difference measurements combined with stable isotope labeling ([U-13C] palmitate) of a mixed meal were used to determine postprandial fatty acid uptake in AT. Results: Body weight was significantly reduced during the WL period (-8.2±0.6 kg, P<0.001), remained stable during the WS period (0.4±0.3 kg, P=0.150), and increased during follow-up (3.5±0.8 kg, P=0.001). Meal-derived in vivo fatty acid uptake dynamics across AT and expression of genes important for fatty acid uptake, storage, and release were not significantly changed during the DI period. Conclusions: Subcutaneous AT does not appear prone to enhanced meal-derived fatty acid uptake after weight loss, nor were fatty acid uptake dynamics detected as related to weight regain