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& Aims: Weight loss is associated with an improvement of insulin sensitivity. Both, a negative energy balance and changes of body composition are integrative components of weight loss interventions. However, the individual impact of these two components on insulin sensitivity and energy metabolism is unclear. Methods: We performed a randomized controlled trial including 80 overweight or obese post-menopausal women. Participants randomly assigned to the intervention group underwent an 800 kcal/ddoi:10.1101/2021.03.25.21254300 fatcat:fgexyhfnangznbguc3pl73xv2e
more »... liquid diet for 2 months followed by four weeks in which the formula diet was substituted by a calorie reduced healthy diet to facilitate further weight loss. This weight loss phase was followed by a 4-week weight maintenance phase, where weight stability was achieved by individualized daily caloric intake without negative energy balance. Volunteers of the control group were instructed to keep their weight stable during the entire period of 4 months. Metabolic phenotyping was performed in both groups at baseline (M0), after weight loss (M3) and after the maintenance period (M4). Additional phenotyping was performed during follow-up at 12 (M12) and 24 months (M24). Primary outcomes were changes of lean body mass (LBM) and changes of insulin sensitivity (ISIClamp) between baseline and M3 and M4. Estimates of energy metabolism were secondary endpoints. Results: No significant changes of body weight or LBM were found in the control group between any time points. A significant reduction of body weight, fat mass (FM) and LBM was found in the intervention group between M0 and M3, while no further change was seen between M3 and M4. Only subjects of the intervention group were characterized by an improvement of the second primary outcome ISIClamp at M3, which was preserved until M4. Notably, a lower resting energy expenditure per LBM (REELBM) at M3 as well as the individual difference of REELBM between M3 and M4 significantly predicted a stronger regain of fat mass during follow-up. Conclusions: In summary, our data demonstrate that modulation of LBM and insulin sensitivity during weight loss is predominantly driven by changes in body weight and body composition, rather than an individual effect of negative energy balance. However, the variance in energy expenditure during negative and steady energy balance indicates a thrifty phenotype, which is highly susceptible to future regain of fat mass.
Obesity is a growing global health problem due to its association with chronic low-grade inflammation contributing to metabolic complications. Multiple studies indicate that white adipose tissue (WAT) inflammation can drive the pathogenesis of type 2 diabetes, including altered levels of cells of the innate and adaptive immune system. However, the function and regulation of both innate and adaptive immune cells in human WAT under conditions of obesity and calorie restriction (CR) is not fullydoi:10.1101/19005934 fatcat:mjddi2pqwnc2zgtgsimqudpdwm
more »... derstood yet. Using a randomized interventional design, we investigated postmenopausal obese women who either underwent CR for three months followed by a 4 weeks phase of weight maintenance or had to maintain a stable weight over the whole study period. A comprehensive immune phenotyping protocol was conducted using validated multiparameter flow cytometry analysis in blood and subcutaneous WAT (SAT) (n=21). The T cell receptor repertoire was analyzed by next generation sequencing (n=20) and cytokine levels were determined in SAT (n=22). Metabolic parameters were determined by hyperinsulinemic-euglycemic clamp and then correlated to immune cell subsets. We found that insulin resistance (IR) correlates significantly with a shift towards the memory T cell compartment in SAT. Among various T cell subsets, predominantly CD8+ effector memory T cells were associated with obesity-related IR. Interestingly, T cell receptor analysis revealed a diverse repertoire in SAT arguing against an antigen-driven intra-SAT expansion of effector memory T cells. Surprisingly, neither inflammatory cytokine levels nor leucocyte subpopulations were significantly altered upon CR. Our findings demonstrate the accumulation of effector memory T cells in obese SAT contributing to chronic inflammation. The long-standing effect of obesity-induced changes in SAT was demonstrated by preserved immune cell composition after short-term CR induced weight loss.
<b><i>Introduction:</i></b> Neuropilin 1 (NRP-1) is a novel co-receptor promoting SARS-CoV-2 infectivity. Animal data indicate a role in trans-endothelial lipid transport and storage. As human data are sparse, we aimed to assess the role of NRP-1 in 2 metabolic active tissues in human obesity and in the context of weight loss-induced short- and long-term metabolic changes. <b><i>Methods:</i></b> After a standardized 12-week weight reduction program, 143 subjects (age >18; body mass indexdoi:10.1159/000520419 pmid:34903696 pmcid:PMC8820135 fatcat:ihsrr3v575eg7ifanhtyvp2wae
more »... 7 kg/m<sup>2</sup>, 78% female) were randomized to a 12-month lifestyle intervention or a control group using a stratified randomization scheme. This was followed by 6-month follow-up without any intervention. Phenotyping was performed before and after weight loss, after 12-month intervention and after subsequent 6 months of follow-up. Tissue-specific insulin sensitivity was estimated by HOMA-IR (whole body and mostly driven by liver), insulin sensitivity index (ISI)<sub>Clamp</sub> (predominantly skeletal muscle), and free fatty acid (FFA) suppression during hyperinsulinemic-euglycemic clamp (FFA<sub>Supp</sub>) (predominantly adipose tissue). NRP-1 mRNA expression was measured in subcutaneous adipose tissue (NRP-1<sub>AT</sub>) and skeletal muscle (NRP-1<sub>SM</sub>) before and after weight loss. <b><i>Results:</i></b> NRP-1 was highly expressed in adipose tissue (7,893 [7,303–8,536] counts), but neither NRP-1<sub>AT</sub> nor NRP-1<sub>SM</sub> were related to estimates of obesity. Higher NRP-1<sub>AT</sub> was associated with stronger FFA<sub>Supp</sub> (<i>r</i> = −0.343, <i>p</i> = 0.003) and a tendency to higher ISI<sub>Clamp</sub> (<i>r</i> = 0.202, <i>p</i> = 0.085). Weight loss induced a decline of NRP-1<sub>AT</sub> but not NRP-1<sub>SM</sub>. This was more pronounced in subjects with stronger reduction of adipose ACE-2 mRNA expression (<i>r</i> = 0.250; <i>p</i> = 0.032) but was not associated with short- and long-term improvement of FFA<sub>Supp</sub> and ISI<sub>Clamp</sub>. <b><i>Conclusion:</i></b> NRP-1<sub>AT</sub> is related to adipose insulin sensitivity in obesity. Weight loss-induced decline of NRP-1<sub>AT</sub> seems not to be involved in metabolic short- and long-term improvements after weight loss. However, weight loss-induced reduction of both NRP-1<sub>AT</sub> and ACE-2<sub>AT</sub> indicates a lower susceptibility of adipose tissue for SARS-CoV-2 after body weight reduction.
High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called 'omics' approaches in the recent years promises to identify molecular markers and to further understand thedoi:10.1186/2043-9113-2-3 pmid:22300499 pmcid:PMC3298809 fatcat:x6qz27el7ja2tczos5mkxyujmq
more »... basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. Methods: We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. Results: We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. Conclusions: We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by highthroughput methods. Age [years] 55.7 ± 11.7 61.5 ± 11.5 Gender [% female] 62.2 Waist circumference [cm] 93.8 ± 13.8 94.6 ± 17.3 Body mass index [kg/m 2 ] 28.6 ± 5.2 29.1 ± 5.3 Fasting glucose [mg] 92.1 ± 11.6 100.5 ± 13.6 Δglucose [mg/(dl · a)] 1.0 ± 2.3 Time between baseline and follow-up [years] 5.6 ± 0.7 Characterisation of the investigated MESY-BEPO sub-cohort (n = 172) at baseline and follow-up. Data are presented as mean ± standard deviation.
The worldwide epidemic of overweight and obesity has led to an increase in associated metabolic comorbidities. Obesity induces chronic low-grade inflammation in white adipose tissue (WAT). However, the function and regulation of both innate and adaptive immune cells in human WAT under conditions of obesity and calorie restriction (CR) is not fully understood yet. Using a randomized interventional design, we investigated postmenopausal overweight or obese female subjects who either underwent CRdoi:10.4049/jimmunol.2000108 pmid:32482712 fatcat:axgkgxuo4ve73a7xtcbzz4dgp4
more »... or 3 mo followed by a 4-wk phase of weight maintenance or had to maintain a stable weight over the whole study period. A comprehensive immune phenotyping protocol was conducted using validated multiparameter flow cytometry analysis in blood and s.c. WAT (SAT). The TCR repertoire was analyzed by next-generation sequencing and cytokine levels were determined in SAT. Metabolic parameters were determined by hyperinsulinemic-euglycemic clamp. We found that insulin resistance correlates significantly with a shift toward the memory T cell compartment in SAT. TCR analysis revealed a diverse repertoire in SAT of overweight or obese individuals. Additionally, whereas weight loss improved systemic insulin sensitivity in the intervention group, SAT displayed no significant improvement of inflammatory parameters (cytokine levels and leukocyte subpopulations) compared with the control group. Our data demonstrate the accumulation of effector memory T cells in obese SAT and an association between systemic glucose homeostasis and inflammatory parameters in obese females. The long-standing effect of obesity-induced changes in SAT was demonstrated by preserved immune cell composition after short-term CR-induced weight loss.
Background While short-term effects of weight loss on quality of life and metabolic aspects appear to be different in metabolically healthy (MHO) and metabolically unhealthy obese (MUO), respective long-term data is still missing. Given the high relevance of long-term changes, we aimed to address these in this post-hoc analysis of the MAINTAIN trial. Methods We analyzed 143 overweight/obese subjects (BMI ≥ 27 kg/m2, age ≥ 18 years) before and after a 3-month weight loss program (≥ 8% weightdoi:10.1186/s12986-022-00660-w pmid:35346256 pmcid:PMC8962471 fatcat:4erclfgcpndhzhzwst4223ghnq
more »... ), after a 12-month period of a randomized weight maintenance intervention (n = 121), and after another 6 months without intervention (n = 112). Subjects were retrospectively grouped into MHO and MUO by the presence of metabolic syndrome and secondarily by estimates of insulin sensitivity (HOMA-IR and ISIClamp). Quality of life (QoL), blood pressure, lipids, HOMA-IR, and ISIClamp were assessed and evaluated using mixed model analyses. Results Despite similar short- and long-term weight loss, weight loss-induced improvement of HOMA-IR was more pronounced in MUO than MHO after 3 months (MHO: 2.4[95%-CI: 1.9–2.9] vs. 1.6[1.1–2.1], p = 0.004; MUO: 3.6[3.2–4.0] vs. 2.0[1.6–2.4], p < 0.001; p = 0.03 for inter-group comparison). After 21 months, the beneficial effect was no longer seen in MHO (2.0[1.5–2.6], p = 1.0), while it remained partially preserved in MUO (2.9[2.4–3.3], p = 0.002). QueryShort-term improvements of lipid parameters were similar in both groups. However, long-term improvements of HDL-cholesterol and triglycerides were only seen in MUO (44.4[41.5–47.4] vs. 49.3[46.2, 52.3] mg/dl, p < 0.001; 176.8[158.9–194.8] vs. 138.8[119.4–158.3] mg/dl, p < 0.001, respectively) but not in MHO. Weight loss-induced improvements in the QoL and particularly the physical health status were maintained in MUO until the end of the trial, while benefits disappeared over time in MHO. Group allocation by HOMA-IR and ISIClamp revealed higher benefits for MUO mainly in parameters of the glucose metabolism and QoL. Conclusions Our data demonstrates stronger and longer-lasting improvements of metabolism and QoL in MUO after weight loss. Trial registration (ClinicalTrials.gov): NCT00850629. Registered 25 February 2009, https://clinicaltrials.gov/ct2/show/NCT00850629.
Objective Betatrophin has been identified as a marker linking liver with beta cell function and lipid metabolism in murine models. Until now, the regulation of circulating betatrophin in humans is not entirely clear. We here analyzed the relation of betatrophin levels to phenotypes of the metabolic syndrome and speculated that renal function might influence circulating betatrophin levels and explain age-dependent changes of betatrophin. Subjects We analyzed blood samples from 535 individualsdoi:10.1371/journal.pone.0173197 pmid:28257453 pmcid:PMC5336269 fatcat:626t3676c5cbbnrtka44dsgr3a
more »... ticipating in the Metabolic Syndrome Berlin Potsdam study. OPEN ACCESS Citation: Maurer L, Schwarz F, Fischer-Rosinsky A, Schlueter N, Brachs S, Möhlig M, et al. (2017) Renal function is independently associated with circulating betatrophin. PLoS ONE 12(3): e0173197.
Chem., 277(10):77667775, 2002. 592  Kristien Van Belle, Jean Herman, Louis Boon, Mark Waer, Ben Sprangers, and Thierry Louat. ... International Journal of Experimental Pathology, 90(3):232-248, 2009. 544  Jörg C Heinrich, Sainitin Donakonda, V Joachim Haupt, Petra Lennig, Yixin Zhang, and Michael 545Schroeder. ...doi:10.1101/678896 fatcat:7mzns6hn65e4dpzgibv5cvxcyu
Deficits in impulse control are discussed as key mechanisms for major worldwide health problems such as drug addiction and obesity. For example, obese subjects have difficulty controlling their impulses to overeat when faced with food items. Here, we investigated the role of neural impulse control mechanisms for dietary success in middle-aged obese subjects. Specifically, we used a food-specific delayed gratification paradigm and functional magnetic resonance imaging to measure eating-relateddoi:10.1016/j.neuroimage.2013.07.028 pmid:23867558 fatcat:bcwuffnzoffdzbq3y6kz7lji5m
more »... pulse-control in middle-aged obese subjects just before they underwent a twelve-week low calorie diet. As expected, we found that subjects with higher behavioral impulse control subsequently lost more weight. Furthermore, brain activity before the diet in VMPFC and DLPFC correlates with subsequent weight loss. Additionally, a connectivity analysis revealed that stronger functional connectivity between these regions is associated with better dietary success and impulse control. Thus, the degree to which subjects can control their eating impulses might depend on the interplay between control regions (DLPFC) and regions signaling the reward of food (VMPFC). This could potentially constitute a general mechanism that also extends to other disorders such as drug addiction or alcohol abuse. (2013). The role of neural impulse control mechanisms for dietary success in obesity. NeuroImage, 83:669-678. Abstract Deficits in impulse control are discussed as key mechanisms for major worldwide health problems such as drug addiction and obesity. For example, obese subjects have difficulty controlling their impulses to overeat when faced with food items. Here, we investigated the role of neural impulse control mechanisms for dietary success in middle-aged obese subjects. Specifically, we used a food-specific delayed gratification paradigm and functional magnetic resonance imaging to measure eating-related impulse-control in middle-aged obese subjects just before they underwent a twelve-week low calorie diet. As expected, we found that subjects with higher behavioural impulse control subsequently lost more weight. Furthermore, brain activity before the diet in VMPFC and DLPFC correlates with subsequent weight loss. Additionally, a connectivity analysis revealed that stronger functional connectivity between these regions is associated with better dietary success and impulse control. Thus, the degree to which subjects can control their eating impulses might depend on the interplay between control regions (DLPFC) and regions signalling the reward of food (VMPFC). This could potentially constitute a general mechanism that also extends to other disorders such as drug addiction or alcohol abuse. 2
Acknowledgements Joachim Spranger was supported by a research group (Molecular Nutrition) ...doi:10.1186/1751-0759-6-3 pmid:22300715 pmcid:PMC3296567 fatcat:dn3g2q4acrbctb776dddbbt34a
Natriuretic peptides (NPs) are a group of peptide-hormones mainly secreted from the heart, signaling via c-GMP coupled receptors. NP are well known for their renal and cardiovascular actions, reducing arterial blood pressure as well as sodium reabsorption. Novel physiological functions have been discovered in recent years, including activation of lipolysis, lipid oxidation, and mitochondrial respiration. Together, these responses promote white adipose tissue browning, increase musculardoi:10.1016/j.pharmthera.2014.04.007 pmid:24780848 fatcat:ke2ze6i3srac7iwspihxi5n5ka
more »... capacity, particularly during physical exercise, and protect against diet-induced obesity and insulin resistance. Exaggerated NP release is a common finding in congestive heart failure. In contrast, NP deficiency is observed in obesity and in type-2 diabetes, pointing to an involvement of NP in the pathophysiology of metabolic disease. Based upon these findings, the NP system holds the potential to be amenable to therapeutical intervention against pandemic diseases such as obesity, insulin resistance, and arterial hypertension. Various therapeutic approaches are currently under development. This paper reviews the current knowledge on the metabolic effects of the NP system and discusses potential therapeutic applications.
Author contribution statement M Hische, P E Schwarz, J Selbig, and J Spranger contributed to design of the study, statistical analyses, and writing of the manuscript. ...doi:10.1530/eje-10-0649 pmid:20693184 fatcat:lrylrmb5s5d7dnciappjcdv6n4
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