To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.
BACKGROUND AND AIM: The role of dietary protein and glycemic index on insulin resistance (based on TyG index) within a nutritional program for weight loss and weight maintenance was examined. METHODS: This study analyzed 744 adults with overweight/obesity within the DIOGenes project. Patients who lost at least 8% of their initial weight (0-8 weeks) after a low-calorie diet (LCD) were randomly assigned to one of five ad libitum diets designed for weight maintenance (8-34 weeks): high/low protein (HP/LP) and high/low glycemic index (HGI/LGI), plus a control. The complete nutritional program (0-34 weeks) included both LCD plus the randomized diets intervention. The TyG index was tested as marker of body mass composition and insulin resistance. RESULTS: In comparison with the LP/HGI diet, the HP/LGI diet induced a greater BMI loss (p < 0.05). ∆TyG was positively associated with resistance to BMI loss (β = 0.343, p = 0.042) during the weight maintenance stage. In patients who followed the HP/LGI diet, TyG (after LCD) correlated with greater BMI loss in the 8-34 weeks period (r = -0.256; p < 0.05) and during the 0-34 weeks intervention (r = -0.222, p < 0.05) periods. ΔTyG1 value was associated with ΔBMI2 (β = 0.932; p = 0.045) concerning the HP/LGI diet. CONCLUSIONS: A HP/LGI diet is beneficial not only for weight maintenance after a LCD, but is also related to IR amelioration as assessed by TyG index changes. Registration Clinical Trials NCT00390637.
- Publikační typ
- časopisecké články MeSH
CONTEXT: Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. OBJECTIVE: To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during 3 steps of a 2-phase dietary intervention (DI). METHODS: AT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day) followed with a 6-month ad libitum randomized DI. Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. Reverse transcription quantitative polymerase chain reaction was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line. RESULTS: During LCD, 5 modules were found, of which 3 included at least 1 bioclinical variable. Change in body mass index (BMI) connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated with changes in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes. CONCLUSION: Network analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.
- MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- genové regulační sítě * MeSH
- hmotnostní úbytek * MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- následné studie MeSH
- obezita metabolismus patologie MeSH
- prognóza MeSH
- redukční dieta * MeSH
- růstový diferenciační faktor 15 genetika metabolismus MeSH
- transkriptom * MeSH
- tuková tkáň metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity. METHODS: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥ 27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss. RESULTS: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks. CONCLUSIONS: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.
- MeSH
- aplikace orální MeSH
- dvojitá slepá metoda MeSH
- hmotnostní úbytek fyziologie MeSH
- hydrogely farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Single nucleotide polymorphisms (SNPs) in FADS1/FADS2 genes are associated with changes in serum and tissue polyunsaturated fatty acid (PUFA) content. PUFA regulate inflammatory signaling pathways in adipose tissue; however, the effect of SNPs in FADS1/FADS2 on adipose tissue inflammation is equivocal. The present study examined if SNPs in FADS1/FADS2 modify human subcutaneous adipose tissue (SAT) fatty acid profiles and the expression of genes associated with inflammation/immune function, lipid metabolism, and cellular differentiation. METHODS: SAT fatty acids and the expression of 117 genes were measured in 174 men and women from the DiOGenes Study using gas chromatography and qRT-PCR, respectively. Associations between fatty acids, gene expression, and SNPs in FADS1/FADS2 were investigated by linear regression and multivariate analysis. RESULTS: Four SNPs (rs174537, rs174546, rs174556, rs174601) in FADS1/FADS2 were significantly associated with SAT fatty acids. All SNPs were in high linkage disequilibrium with the commonly reported rs174537 SNP in FADS1. Minor allele carriers for rs174537 (GT+TT) had reduced 20:4n-6 (p = 1.74E-5), lower delta-5 desaturase enzyme activity (p = 2.09E-9), and lower FADS1 gene expression (p = 0.03) compared to major GG carriers. Multivariate analysis revealed that 20:4n-6 and 20:3n-6 explained ~19% of the variance between rs174537 genotypes, while gene expression explained <7%. Receiver operating characteristic (ROC) curves indicated that rs174537 genotype can be distinguished with SAT fatty acids (AUC = 0.842), but not gene expression (AUC = 0.627). No differences in SAT inflammatory gene expression were observed between rs174537 genotypes. SAT 20:3n-6 levels were positively correlated with the expression of several inflammatory genes, and inversely correlated with FADS1 expression. CONCLUSION: This study showed that FADS1 genotype is distinguished by SAT fatty acid profiles, but not inflammatory gene expression.
- MeSH
- buněčná diferenciace genetika MeSH
- desaturasy mastných kyselin genetika metabolismus MeSH
- dospělí MeSH
- exprese genu MeSH
- genotyp MeSH
- imunitní systém MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- mastné kyseliny genetika MeSH
- metabolismus lipidů genetika MeSH
- multigenová rodina genetika MeSH
- multivariační analýza MeSH
- obezita genetika MeSH
- podkožní tuk metabolismus MeSH
- zánět genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders. OBJECTIVES: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss. METHODS: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting. RESULTS: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor α, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion. CONCLUSIONS: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.
- MeSH
- adipokiny genetika metabolismus MeSH
- apolipoproteiny M genetika metabolismus MeSH
- kalorická restrikce MeSH
- klinické zkoušky jako téma MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- obezita dietoterapie genetika metabolismus MeSH
- průřezové studie MeSH
- tukové buňky metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
People with obesity often struggle to maintain their weight loss after a weight loss period. Furthermore, the effect of weight loss on appetite and food preferences remains unclear. Hence this study investigated the effect of weight loss on subjective appetite and food preferences in healthy, overweight and obese volunteers. A subgroup of adult participants (n = 123) from the Diet Obesity and Genes (DiOGenes) study (subgroup A) was recruited from across six European countries. Participants lost ≥8% of initial body weight during an 8-week low calorie diet (LCD). Subjective appetite and food preferences were measured before and after the LCD, in response to a standardized meal test, using visual analogue rating scales (VAS) and the Leeds Food Choice Questionnaire (FCQ). After the LCD, participants reported increased fullness (p < 0.05), decreased desire to eat (p < 0.05) and decreased prospective consumption (p < 0.05) after consuming the test meal. An interaction effect (visit x time) was found for hunger ratings (p < 0.05). Area under the curve (AUC) for hunger, desire to eat and prospective consumption was decreased by 18.1%, 20.2% and 21.1% respectively whereas AUC for fullness increased by 13.9%. Preference for low-energy products measured by the Food Preference Checklist (FPC) decreased by 1.9% before the test meal and by 13.5% after the test meal (p < 0.05). High-carbohydrate and high-fat preference decreased by 11.4% and 16.2% before the test meal and by 17.4% and 22.7% after the meal (p < 0.05). No other effects were observed. These results suggest that LCD induced weight loss decreases the appetite perceptions of overweight volunteers whilst decreasing their preference for high-fat-, high-carbohydrate-, and low-energy products.
- MeSH
- chuť k jídlu * MeSH
- dietní sacharidy aplikace a dávkování MeSH
- dietní tuky aplikace a dávkování MeSH
- dospělí MeSH
- energetický příjem MeSH
- hlad MeSH
- hmotnostní úbytek fyziologie MeSH
- index tělesné hmotnosti MeSH
- jídla MeSH
- kalorická restrikce * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nadváha MeSH
- obezita * dietoterapie psychologie MeSH
- plocha pod křivkou MeSH
- preference v jídle * MeSH
- přijímání potravy MeSH
- prospektivní studie MeSH
- redukční dieta * MeSH
- udržení hmotnosti MeSH
- zpráva o sobě MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Evropa MeSH
An increase in dietary protein intake has been shown to improve weight loss maintenance in the DIOGenes trial. Here, we analysed whether the source of the dietary proteins influenced changes in body weight, body composition, and cardiometabolic risk factors during the weight maintenance period while following an energy-restricted diet. 489 overweight or obese participants of the DIOGenes trial from eight European countries were included. They successfully lost >8% of body weight and subsequently completed a six month weight maintenance period, in which they consumed an ad libitum diet varying in protein content and glycemic index. Dietary intake was estimated from three-day food diaries. A higher plant protein intake with a proportional decrease in animal protein intake did not affect body weight maintenance or cardiometabolic risk factors. A higher plant protein intake from non-cereal products instead of cereal products was associated with benefits for body weight maintenance and blood pressure. Substituting meat protein for protein from other animal sources increased insulin and HOMA-IR (homeostasis model assessment of insulin resistance). This analysis suggests that not only the amount of dietary proteins, but also the source may be important for weight and cardiometabolic risk management. However, randomized trials are needed to test the causality of these associations.
- MeSH
- analýza potravin * MeSH
- dietní proteiny aplikace a dávkování analýza MeSH
- dospělí MeSH
- energetický příjem MeSH
- hmotnostní přírůstek MeSH
- hmotnostní úbytek MeSH
- lidé MeSH
- redukční dieta MeSH
- rizikové faktory MeSH
- složení těla * MeSH
- tělesná hmotnost * MeSH
- udržení hmotnosti MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Maintenance of weight loss and associated cardiovascular benefits after following energy-restricted diets is still a challenging field, and thorough investigation is needed. The present research aimed to determine the role of protein and gender in relation to two different intervention models related to food supply, in a weight maintenance trial. SUBJECTS AND METHODS: The DiOGenes trial was a long-term, multicenter, randomized, dietary intervention study, conducted in eight European countries (Clinical Trials.gov, NCT00390637), focusing on assessing the effectiveness of weight maintenance over 6 months. This secondary analysis intended to evaluate the different benefits for weight maintenance and cardiometabolic markers of two dietary advice delivery models: "shop + instruction intervention" vs "instruction-alone intervention," which were further categorized for gender and macronutrient intake. RESULTS: The weight maintenance intervention based on different macronutrient intake showed, independently of the advice delivery model, in both sexes that higher protein consumption was more effective for weight stability, showing better results in obese women (low protein: 1.65 kg in males and 0.73 Kg in females vs high protein: 1.45 kg in males and -0.93 Kg in females) . Measurements concerning cardiovascular risk markers from subjects on both structured models produced similar trends in the subsequent follow-up period, with a lower rebound in women for most of the markers analyzed. CONCLUSION: The reported dietary benefits for weight sustainability should be ascribed to the macronutrient distribution (higher protein diets) rather than to the structured mode of delivery. Higher weight regain in males was noted, as well as a metabolic divergence attributable to the sex, with a better biochemical outcome in women.
- MeSH
- dieta * MeSH
- dietní proteiny aplikace a dávkování farmakologie MeSH
- dietoterapie metody MeSH
- dospělí MeSH
- genderová identita MeSH
- hmotnostní přírůstek účinky léků MeSH
- hmotnostní úbytek MeSH
- kardiovaskulární nemoci etiologie prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- obchod MeSH
- rizikové faktory MeSH
- sexuální faktory MeSH
- stravovací zvyklosti * MeSH
- udržení hmotnosti účinky léků MeSH
- výsledek terapie MeSH
- výživové doporučené dávky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Dairy products have previously been reported to be associated with beneficial effects on body weight and metabolic risk markers. Moreover, primary data from the Diet, Obesity and Genes (DiOGenes) study indicate a weight-maintaining effect of a high-protein-low-glycaemic index diet. The objective of the present study was to examine putative associations between consumption of dairy proteins and changes in body weight and metabolic risk markers after weight loss in obese and overweight adults. Results were based on secondary analyses of data obtained from overweight and obese adults who completed the DiOGenes study. The study consisted of an 8-week weight-loss phase and a 6-month weight-maintenance (WM) phase, where the subjects were given five different diets varying in protein content and glycaemic index. In the present study, data obtained from all the subjects were pooled. Dairy protein intake was estimated from 3 d dietary records at two time points (week 4 and week 26) during the WM phase. Body weight and metabolic risk markers were determined at baseline (week -9 to -11) and before and at the end of the WM phase (week 0 and week 26). Overall, no significant associations were found between consumption of dairy proteins and changes in body weight and metabolic risk markers. However, dairy protein intake tended to be negatively associated with body weight gain (P=0·08; β=-0·17), but this was not persistent when controlled for total protein intake, which indicates that dairy protein adds no additional effect to the effect of total protein. Therefore, the present study does not report that dairy proteins are more favourable than other proteins for body weight regulation.
- MeSH
- biologické markery MeSH
- diabetes mellitus 1. typu epidemiologie etiologie prevence a kontrola MeSH
- dietní proteiny aplikace a dávkování škodlivé účinky MeSH
- glykemický index MeSH
- hmotnostní úbytek MeSH
- index tělesné hmotnosti MeSH
- kardiovaskulární nemoci epidemiologie etiologie prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- mléčné bílkoviny aplikace a dávkování škodlivé účinky MeSH
- nadváha dietoterapie patofyziologie prevence a kontrola MeSH
- nízkoproteinová dieta MeSH
- obezita dietoterapie patofyziologie prevence a kontrola MeSH
- podpora zdraví * MeSH
- recidiva MeSH
- redukční dieta MeSH
- riziko MeSH
- sekundární prevence MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Geografické názvy
- Evropa MeSH
