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1.
Int J Obes (Lond) ; 48(7): 964-972, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38459259

RESUMO

BACKGROUND/OBJECTIVES: Proinflammatory cytokines are increased in obese adipose tissue, including inflammasome key masters. Conversely, IL-18 protects against obesity and metabolic dysfunction. We focused on the IL-18 effect in controlling adipose tissue remodeling and metabolism. MATERIALS/SUBJECTS AND METHODS: We used C57BL/6 wild-type (WT) and interleukine-18 deficient (IL-18-/-) male mice fed a chow diet and samples from bariatric surgery patients. RESULTS: IL-18-/- mice showed increased adiposity and proinflammatory cytokine levels in adipose tissue, leading to glucose intolerance. IL-18 was widely secreted by stromal vascular fraction but not adipocytes from mice's fatty tissue. Chimeric model experiments indicated that IL-18 controls adipose tissue expansion through its presence in tissues other than bone marrow. However, IL-18 maintains glucose homeostasis when present in bone marrow cells. In humans with obesity, IL-18 expression in omental tissue was not correlated with BMI or body fat mass but negatively correlated with IRS1, GLUT-4, adiponectin, and PPARy expression. Also, the IL-18RAP receptor was negatively correlated with IL-18 expression. CONCLUSIONS: IL-18 signaling may control adipose tissue expansion and glucose metabolism, as its absence leads to spontaneous obesity and glucose intolerance in mice. We suggest that resistance to IL-18 signaling may be linked with worse glucose metabolism in humans with obesity.


Assuntos
Tecido Adiposo , Interleucina-18 , Camundongos Endogâmicos C57BL , Obesidade , Animais , Interleucina-18/metabolismo , Camundongos , Masculino , Tecido Adiposo/metabolismo , Humanos , Obesidade/metabolismo , Intolerância à Glucose/metabolismo , Modelos Animais de Doenças , Camundongos Knockout
2.
Curr Opin Clin Nutr Metab Care ; 27(4): 361-371, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38260940

RESUMO

PURPOSE OF REVIEW: Understanding the spectrum of drivers that influence the gut microbiome (GM) remains a crucial field of investigation. Among these factors, diet has received particular attention, as it could explain up to 20% of the variability in GM composition between individuals. This review focuses on the complex relationships between different dietary patterns and GM in humans, based on recent findings. RECENT FINDINGS: Current evidence underscores the multifaceted impact of diet on GM richness, diversity, and overall composition. Key contributing factors encompass dietary habits, nutritional interventions, food quality and variety, macronutrient distribution, timing of feeding, and selective exclusion of certain foods. SUMMARY: The intricate interplay between diet and GM is of fundamental importance in shaping the interaction between the host and the environment. Further understanding the causal impact of diet on GM has promising potential for the advancement of strategies to promote health and mitigate cardio-metabolic disease risks through dietary interventions. GRAPHICAL ABSTRACT: http://links.lww.com/COCN/A21.


Assuntos
Dieta , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Dieta/métodos , Comportamento Alimentar/fisiologia , Interações entre Hospedeiro e Microrganismos/fisiologia
3.
Ann Endocrinol (Paris) ; 85(3): 175-178, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38871506

RESUMO

This lecture delves into the pivotal role of adipose tissue in obesity and its response to weight loss, particularly via bariatric surgery. Adipose tissue, responsible for storing excess energy, undergoes significant changes during obesity, marked by inflammation and fibrosis. Bariatric surgery, serving as a model, allow the exploration of adipose tissue remodeling post-weight loss, inducing metabolic and fibro-inflammatory shifts. Despite successful weight loss, inflammation and fibrosis persist, as evidenced by changes in immune cells, altered cytokine profiles and the accumulation of extracellular matrix (ECM). Unfortunately, these lingering effects impair the normal adipose tissue function. In this context, adipose progenitors, an heterogenous resident population of mesenchymal stromal cells, display functions important to fibrosis development, capable of differentiating into myofibroblasts and contributing to ECM deposition. Particularly, a distinct subpopulation of adipose progenitors with high CD9 expression (CD9high) is associated with fibrosis and insulin resistance in human obesity. The persistence of fibrosis post-weight loss poses challenges, correlating with metabolic dysfunction despite improved glucose tolerance. A comprehensive understanding of the mechanisms driving adipose tissue remodeling and fibrosis post-weight loss is imperative for the development of effective treatments for obesity. The intricate interplay between adipose tissue, inflammation, and fibrosis underscores the necessity for further in-depth research to elucidate these mechanisms and formulate targeted therapies for obesity-related complications.


Assuntos
Tecido Adiposo , Cirurgia Bariátrica , Fibrose , Obesidade , Redução de Peso , Humanos , Cirurgia Bariátrica/métodos , Tecido Adiposo/metabolismo , Obesidade/cirurgia , Obesidade/metabolismo , Redução de Peso/fisiologia , Inflamação/patologia , Resistência à Insulina/fisiologia
4.
Orphanet J Rare Dis ; 19(1): 84, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395939

RESUMO

BACKGROUND: The determinants of early-onset obesity (< 6 years) are not completely elucidated, however eating behavior has a central role. To date no study has explored eating behavior in children with severe, early-onset obesity. Self-administered questionnaire data from these children were examined to evaluate eating behavior and the etiology of early-onset obesity. METHODS: Children with severe, early-onset obesity (body mass index [BMI] > International Obesity Task Force [IOTF] 30) of different etiologies (hypothalamic obesity [HO], intellectual disability with obesity [IDO], common polygenic obesity [CO]) were prospectively included. BMI history and responses from the Dykens' Hyperphagia Questionnaire and an in-house Impulsivity Questionnaire at first visit were compared between groups. RESULTS: This cohort of 75 children (39 girls; mean age ± standard deviation [SD] 10.8 ± 4.4 years) had severe, early-onset obesity at an age of 3.8 ± 2.7 years, with a BMI Z-score of 4.9 ± 1.5. BMI history varied between the 3 groups, with earlier severe obesity in the HO group versus 2 other groups (BMI > IOTF40 at 3.4 ± 1.6 vs. 4.6 ± 1.6 and 8.4 ± 4.1 years for the IDO and CO groups, respectively [P < 0.01]). Absence of adiposity rebound was more prevalent in the HO group (87% vs. 63% and 33% for the IDO and CO groups, respectively [P < 0.01]). The Dykens' mean total score for the cohort was 22.1 ± 7.2 with no significant between-group differences. Hyperphagia (Dykens' score > 19) and impulsivity (score > 7) were found in 50 (67%) and 11 children (15%), respectively, with no difference between the HO, IDO and CO groups regarding the number of patients with hyperphagia (10 [67%], 14 [74%], and 26 [63%] children, respectively) or impulsivity (2 [13%], 1 [7%], and 8 [19%] children, respectively). Children with food impulsivity had significantly higher total and severity scores on the Dykens' Questionnaire versus those without impulsivity. CONCLUSION: The Dykens' and Impulsivity questionnaires can help diagnose severe hyperphagia with/without food impulsivity in children with early-onset obesity, regardless of disease origin. Their systematic use can allow more targeted management of food access control in clinical practice and monitor the evolution of eating behavior in the case of innovative therapeutic targeting hyperphagia.


Assuntos
Hiperfagia , Obesidade , Criança , Feminino , Humanos , Lactente , Pré-Escolar , Hiperfagia/complicações , Obesidade/etiologia , Índice de Massa Corporal , Comportamento Alimentar , Comportamento Impulsivo , Inquéritos e Questionários
5.
Metabolism ; 150: 155712, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37884078

RESUMO

The study of the gut microbiome holds great promise for understanding and treating metabolic diseases, as its functions and derived metabolites can influence the metabolic status of the host. While research on the fecal microbiome has provided valuable insights, it tells us only part of the story. This limitation arises from the substantial variations in microorganism distribution throughout the gastrointestinal tract due to changes in physicochemical conditions. Thus, relying solely on the fecal microbiome may not be sufficient to draw comprehensive conclusions about metabolic diseases. The proximal part of the small intestine, particularly the jejunum, indeed, serves as the crucial site for digestion and absorption of nutrients, suggesting a potential role of its microbiome in metabolic regulation. Unfortunately, it remains relatively underexplored due to limited accessibility. This review presents current evidence regarding the relationships between the microbiome in the upper small intestine and various phenotypes, focusing on obesity and type 2 diabetes, in both humans and rodents. Research on humans is still limited with variability in the population and methods used. Accordingly, to better understand the role of the whole gut microbiome in metabolic diseases, studies exploring the human microbiome in different niches are needed.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Microbiota , Humanos , Doenças Metabólicas/metabolismo , Obesidade/terapia , Intestino Delgado/metabolismo
6.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1869(4): 159470, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38423452

RESUMO

Hyaluronan is an important extracellular matrix component, with poorly documented physiological role in the context of lipid-rich adipose tissue. We have investigated the global impact of hyaluronan removal from adipose tissue environment by in vitro exposure to exogenous hyaluronidase (or heat inactivated enzyme). Gene set expression analysis from RNA sequencing revealed downregulated adipogenesis as a main response to hyaluronan removal from human adipose tissue samples, which was confirmed by hyaluronidase-mediated inhibition of adipocyte differentiation in the 3T3L1 adipose cell line. Hyaluronidase exposure starting from the time of induction with the differentiation cocktail reduced lipid accumulation in mature adipocytes, limited the expression of terminal differentiation marker genes, and impaired the early induction of co-regulated Cebpa and Pparg mRNA. Reduction of Cebpa and Pparg expression by exogenous hyaluronidase was also observed in cultured primary preadipocytes from subcutaneous, visceral or brown adipose tissue of mice. Mechanistically, inhibition of adipogenesis by hyaluronan removal was not caused by changes in osmotic pressure or cell inflammatory status, could not be mimicked by exposure to threose, a metabolite generated by hyaluronan degradation, and was not linked to alteration in endogenous Wnt ligands expression. Rather, we observed that hyaluronan removal associated with disrupted primary cilia dynamics, with elongated cilium and higher proportions of preadipocytes that remained ciliated in hyaluronidase-treated conditions. Thus, our study points to a new link between ciliogenesis and hyaluronan impacting adipose tissue development.


Assuntos
Cílios , Ácido Hialurônico , Camundongos , Humanos , Animais , Ácido Hialurônico/metabolismo , Cílios/metabolismo , PPAR gama/metabolismo , Hialuronoglucosaminidase/genética , Hialuronoglucosaminidase/metabolismo , Diferenciação Celular/fisiologia , Tecido Adiposo Marrom/metabolismo , Lipídeos
7.
Nat Commun ; 15(1): 5413, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926424

RESUMO

Diet composition impacts metabolic health and is now recognized to shape the immune system, especially in the intestinal tract. Nutritional imbalance and increased caloric intake are induced by high-fat diet (HFD) in which lipids are enriched at the expense of dietary fibers. Such nutritional challenge alters glucose homeostasis as well as intestinal immunity. Here, we observed that short-term HFD induced dysbiosis, glucose intolerance and decreased intestinal RORγt+ CD4 T cells, including peripherally-induced Tregs and IL17-producing (Th17) T cells. However, supplementation of HFD-fed male mice with the fermentable dietary fiber fructooligosaccharides (FOS) was sufficient to maintain RORγt+ CD4 T cell subsets and microbial species known to induce them, alongside having a beneficial impact on glucose tolerance. FOS-mediated normalization of Th17 cells and amelioration of glucose handling required the cDC2 dendritic cell subset in HFD-fed animals, while IL-17 neutralization limited FOS impact on glucose tolerance. Overall, we uncover a pivotal role of cDC2 in the control of the immune and metabolic effects of FOS in the context of HFD feeding.


Assuntos
Células Dendríticas , Dieta Hiperlipídica , Homeostase , Camundongos Endogâmicos C57BL , Oligossacarídeos , Animais , Oligossacarídeos/farmacologia , Dieta Hiperlipídica/efeitos adversos , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Masculino , Camundongos , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/efeitos dos fármacos , Glucose/metabolismo , Interleucina-17/metabolismo , Fibras na Dieta/farmacologia , Intolerância à Glucose/imunologia , Intolerância à Glucose/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Disbiose/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos
8.
JCI Insight ; 9(9)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38716728

RESUMO

The importance of the proper localization of most receptors at the cell surface is often underestimated, although this feature is essential for optimal receptor response. Endospanin 1 (Endo1) (also known as OBRGRP or LEPROT) is a protein generated from the same gene as the human leptin receptor and regulates the trafficking of proteins to the surface, including the leptin receptor. The systemic role of Endo1 on whole-body metabolism has not been studied so far. Here, we report that general Endo1-KO mice fed a high-fat diet develop metabolically healthy obesity with lipid repartitioning in organs and preferential accumulation of fat in adipose tissue, limited systematic inflammation, and better controlled glucose homeostasis. Mechanistically, Endo1 interacts with the lipid translocase CD36, thus regulating its surface abundance and lipid uptake in adipocytes. In humans, the level of Endo1 transcripts is increased in the adipose tissue of patients with obesity, but low levels rather correlate with a profile of metabolically healthy obesity. We suggest here that Endo1, most likely by controlling CD36 cell surface abundance and lipid uptake in adipocytes, dissociates obesity from diabetes and that its absence participates in metabolically healthy obesity.


Assuntos
Tecido Adiposo , Antígenos CD36 , Dieta Hiperlipídica , Camundongos Knockout , Obesidade , Animais , Feminino , Humanos , Masculino , Camundongos , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Antígenos CD36/metabolismo , Antígenos CD36/genética , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Metabolismo dos Lipídeos/genética , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/genética
9.
Clin Obes ; 14(3): e12659, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602039

RESUMO

Nearly 90 clinicians and researchers from around the world attended the first IMPROVE 2022 International Meeting on Pathway-Related Obesity. Delegates attended in person or online from across Europe, Argentina and Israel to hear the latest scientific and clinical developments in hyperphagia and severe, early-onset obesity, and set out a vision of excellence for the future for improving the diagnosis, treatment, and care of patients with melanocortin-4 receptor (MC4R) pathway-related obesity. The meeting co-chair Peter Kühnen, Charité Universitätsmedizin Berlin, Germany, indicated that change was needed with the rapidly increasing prevalence of obesity and the associated complications to improve the understanding of the underlying mechanisms and acknowledge that monogenic forms of obesity can play an important role, providing insights that can be applied to a wider group of patients with obesity. World-leading experts presented the latest research and led discussions on the underlying science of obesity, diagnosis (including clinical and genetic approaches such as the role of defective MC4R signalling), and emerging clinical data and research with targeted pharmacological approaches. The aim of the meeting was to agree on the questions that needed to be addressed in future research and to ensure that optimised diagnostic work-up was used with new genetic testing tools becoming available. This should aid the planning of new evidence-based treatment strategies for the future, as explained by co-chair Martin Wabitsch, Ulm University Medical Center, Germany.


Assuntos
Obesidade , Receptor Tipo 4 de Melanocortina , Humanos , Hiperfagia , Obesidade/terapia , Receptor Tipo 4 de Melanocortina/genética , Receptor Tipo 4 de Melanocortina/metabolismo , Transdução de Sinais
10.
BMC Med Genomics ; 17(1): 209, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138568

RESUMO

BACKGROUND: Persons living with HIV (PWH) harbor an altered gut microbiome (higher abundance of Prevotella and lower abundance of Bacillota and Ruminococcus lineages) compared to non-infected individuals. Some of these alterations are linked to sexual preference and others to the HIV infection. The relationship between these lineages and metabolic alterations, often present in aging PWH, has been poorly investigated. METHODS: In this study, we compared fecal metagenomes of 25 antiretroviral-treatment (ART)-controlled PWH to three independent control groups of 25 non-infected matched individuals by means of univariate analyses and machine learning methods. Moreover, we used two external datasets to validate predictive models of PWH classification. Next, we searched for associations between clinical and biological metabolic parameters with taxonomic and functional microbiome profiles. Finally, we compare the gut microbiome in 7 PWH after a 17-week ART switch to raltegravir/maraviroc. RESULTS: Three major enterotypes (Prevotella, Bacteroides and Ruminococcaceae) were present in all groups. The first Prevotella enterotype was enriched in PWH, with several of characteristic lineages associated with poor metabolic profiles (low HDL and adiponectin, high insulin resistance (HOMA-IR)). Conversely butyrate-producing lineages were markedly depleted in PWH independently of sexual preference and were associated with a better metabolic profile (higher HDL and adiponectin and lower HOMA-IR). Accordingly with the worst metabolic status of PWH, butyrate production and amino-acid degradation modules were associated with high HDL and adiponectin and low HOMA-IR. Random Forest models trained to classify PWH vs. control on taxonomic abundances displayed high generalization performance on two external holdout datasets (ROC AUC of 80-82%). Finally, no significant alterations in microbiome composition were observed after switching to raltegravir/maraviroc. CONCLUSION: High resolution metagenomic analyses revealed major differences in the gut microbiome of ART-controlled PWH when compared with three independent matched cohorts of controls. The observed marked insulin resistance could result both from enrichment in Prevotella lineages, and from the depletion in species producing butyrate and involved into amino-acid degradation, which depletion is linked with the HIV infection.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV , Resistência à Insulina , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Fezes/microbiologia , Antirretrovirais/uso terapêutico , Metagenoma
11.
Cardiovasc Res ; 120(4): 372-384, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38289866

RESUMO

AIMS: Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVDs). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes. METHODS AND RESULTS: We included cross-sectional data from 3860 individuals without CVD history from 6 ethnicities living in the Amsterdam region participating in the prospective Healthy Life in Urban Setting (HELIUS) study. Genetic variants were genotyped, faecal gut microbiota were profiled, and blood and anthropometric parameters were measured. A machine learning approach was used to assess the relationship between CVD risk (Framingham score) and gut microbiota stratified by ethnicity. Potential causal relationships between gut microbiota composition and CVD were inferred by performing two-sample Mendelian randomization with hard CVD events from the Pan-UK Biobank and microbiome genome-wide association studies summary data from a subset of the HELIUS cohort (n = 4117). Microbial taxa identified to be associated with CVD by machine learning and Mendelian randomization were often ethnic-specific, but some concordance across ethnicities was found. The microbes Akkermansia muciniphila and Ruminococcaceae UCG-002 were protective against ischaemic heart disease in African-Surinamese and Moroccans, respectively. We identified a strong inverse association between blood lipids, CVD risk, and the combined abundance of the correlated microbes Christensenellaceae-Methanobrevibacter-Ruminococcaceae (CMR). The CMR cluster was also identified in two independent cohorts and the association with triglycerides was replicated. CONCLUSION: Certain gut microbes can have a potentially causal relationship with CVD events, with possible ethnic-specific effects. We identified a trophic network centred around Christensenellaceae, Methanobrevibacter, and various Ruminococcaceae, frequently lacking in South-Asian Surinamese, to be protective against CVD risk and associated with low triglyceride levels.


Assuntos
Doenças Cardiovasculares , Etnicidade , Microbioma Gastrointestinal , Humanos , Bactérias/genética , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/microbiologia , Estudos Transversais , Estudo de Associação Genômica Ampla , Lipídeos , Estudos Prospectivos , Fatores de Risco , Países Baixos
12.
Gut Microbes ; 16(1): 2370616, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38961712

RESUMO

Amino acids, metabolized by host cells as well as commensal gut bacteria, have signaling effects on host metabolism. Oral supplementation of the essential amino acid histidine has been shown to exert metabolic benefits. To investigate whether dietary histidine aids glycemic control, we performed a case-controlled parallel clinical intervention study in participants with type 2 diabetes (T2D) and healthy controls. Participants received oral histidine for seven weeks. After 2 weeks of histidine supplementation, the microbiome was depleted by antibiotics to determine the microbial contribution to histidine metabolism. We assessed glycemic control, immunophenotyping of peripheral blood mononucelar cells (PBMC), DNA methylation of PBMCs and fecal gut microbiota composition. Histidine improves several markers of glycemic control, including postprandial glucose levels with a concordant increase in the proportion of MAIT cells after two weeks of histidine supplementation. The increase in MAIT cells was associated with changes in gut microbial pathways such as riboflavin biosynthesis and epigenetic changes in the amino acid transporter SLC7A5. Associations between the microbiome and MAIT cells were replicated in the MetaCardis cohort. We propose a conceptual framework for how oral histidine may affect MAIT cells via altered gut microbiota composition and SLC7A5 expression in MAIT cells directly and thereby influencing glycemic control. Future studies should focus on the role of flavin biosynthesis intermediates and SLC7A5 modulation in MAIT cells to modulate glycemic control.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Histidina , Células T Invariantes Associadas à Mucosa , Humanos , Histidina/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Pessoa de Meia-Idade , Masculino , Feminino , Células T Invariantes Associadas à Mucosa/imunologia , Células T Invariantes Associadas à Mucosa/metabolismo , Controle Glicêmico , Suplementos Nutricionais , Estudos de Casos e Controles , Fezes/microbiologia , Glicemia/metabolismo , Idoso , Adulto , Bactérias/classificação , Bactérias/metabolismo , Bactérias/genética , Administração Oral , Metilação de DNA
13.
Nat Metab ; 6(7): 1329-1346, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39009762

RESUMO

Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis. In human white adipocytes, reductions in glutaminase activity promote aerobic glycolysis and mitochondrial oxidative capacity via increases in hypoxia-inducible factor 1α abundance, lactate levels and p38 mitogen-activated protein kinase signalling. Systemic glutaminase inhibition in male and female mice, or genetically in adipocytes of male mice, triggers the activation of thermogenic gene programs in inguinal adipocytes. Consequently, the knockout mice display higher energy expenditure and improved glucose tolerance compared to control littermates, even under high-fat diet conditions. Altogether, our findings highlight white adipocyte glutamine turnover as an important determinant of energy expenditure and metabolic health.


Assuntos
Adipócitos , Metabolismo Energético , Glutaminase , Camundongos Knockout , Animais , Glutaminase/metabolismo , Camundongos , Humanos , Masculino , Adipócitos/metabolismo , Feminino , Obesidade/metabolismo , Resistência à Insulina , Glutamina/metabolismo , Dieta Hiperlipídica , Glicólise
14.
Sci Rep ; 13(1): 22386, 2023 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-38104165

RESUMO

The gut microbiome plays a significant role in the development of Type 2 Diabetes Mellitus (T2DM), but the functional mechanisms behind this association merit deeper investigation. Here, we used the nanopore sequencing technology for metagenomic analyses to compare the gut microbiome of individuals with T2DM from the United Arab Emirates (n = 40) with that of control (n = 44). DMM enterotyping of the cohort resulted concordantly with previous results, in three dominant groups Bacteroides (K1), Firmicutes (K2), and Prevotella (K3) lineages. The diversity analysis revealed a high level of diversity in the Firmicutes group (K2) both in terms of species richness and evenness (Wilcoxon rank-sum test, p value < 0.05 vs. K1 and K3 groups), consistent with the Ruminococcus enterotype described in Western populations. Additionally, functional enrichment analyses of KEGG modules showed significant differences in abundance between individuals with T2DM and controls (FDR < 0.05). These differences include modules associated with the degradation of amino acids, such as arginine, the degradation of urea as well as those associated with homoacetogenesis. Prediction analysis with the Predomics approach suggested potential biomarkers for T2DM, including a balance between a depletion of Enterococcus faecium and Blautia lineages with an enrichment of Absiella spp or Eubacterium limosum in T2DM individuals, highlighting the potential of metagenomic analysis in predicting predisposition to diabetic cardiomyopathy in T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Microbioma Gastrointestinal , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal/genética , Firmicutes , Metagenoma
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