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1.
Front Immunol ; 15: 1360065, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558823

RESUMO

Mounting evidence progressively appreciates the vital interplay between immunity and metabolism in a wide array of immunometabolic chronic disorders, both autoimmune and non-autoimmune mediated. The immune system regulates the functioning of cellular metabolism within organs like the brain, pancreas and/or adipose tissue by sensing and adapting to fluctuations in the microenvironment's nutrients, thereby reshaping metabolic pathways that greatly impact a pro- or anti-inflammatory immunophenotype. While it is agreed that the immune system relies on an adequate nutritional status to function properly, we are only just starting to understand how the supply of single or combined nutrients, all of them termed immunonutrients, can steer immune cells towards a less inflamed, tolerogenic immunophenotype. Polyphenols, a class of secondary metabolites abundant in Mediterranean foods, are pharmacologically active natural products with outstanding immunomodulatory actions. Upon binding to a range of receptors highly expressed in immune cells (e.g. AhR, RAR, RLR), they act in immunometabolic pathways through a mitochondria-centered multi-modal approach. First, polyphenols activate nutrient sensing via stress-response pathways, essential for immune responses. Second, they regulate mammalian target of rapamycin (mTOR)/AMP-activated protein kinase (AMPK) balance in immune cells and are well-tolerated caloric restriction mimetics. Third, polyphenols interfere with the assembly of NLR family pyrin domain containing 3 (NLRP3) in endoplasmic reticulum-mitochondria contact sites, inhibiting its activation while improving mitochondrial biogenesis and autophagosome-lysosome fusion. Finally, polyphenols impact chromatin remodeling and coordinates both epigenetic and metabolic reprogramming. This work moves beyond the well-documented antioxidant properties of polyphenols, offering new insights into the multifaceted nature of these compounds. It proposes a mechanistical appraisal on the regulatory pathways through which polyphenols modulate the immune response, thereby alleviating chronic low-grade inflammation. Furthermore, it draws parallels between pharmacological interventions and polyphenol-based immunonutrition in their modes of immunomodulation across a wide spectrum of socioeconomically impactful immunometabolic diseases such as Multiple Sclerosis, Diabetes (type 1 and 2) or even Alzheimer's disease. Lastly, it discusses the existing challenges that thwart the translation of polyphenols-based immunonutritional interventions into long-term clinical studies. Overcoming these limitations will undoubtedly pave the way for improving precision nutrition protocols and provide personalized guidance on tailored polyphenol-based immunonutrition plans.


Assuntos
Mitocôndrias , Polifenóis , Humanos , Polifenóis/farmacologia , Mitocôndrias/metabolismo , Sistema Imunitário/metabolismo , Inflamação/metabolismo , Tecido Adiposo/metabolismo
2.
Physiol Rep ; 12(7): e15995, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38561245

RESUMO

Exercise has different effects on different tissues in the body, the sum of which may determine the response to exercise and the health benefits. In the present study, we aimed to investigate whether physical training regulates transcriptional network communites common to both skeletal muscle (SM) and subcutaneous adipose tissue (SAT). Eight such shared transcriptional communities were found in both tissues. Eighteen young overweight adults voluntarily participated in 7 weeks of combined strength and endurance training (five training sessions per week). Biopsies were taken from SM and SAT before and after training. Five of the network communities were regulated by training in SM but showed no change in SAT. One community involved in insulin- AMPK signaling and glucose utilization was upregulated in SM but downregulated in SAT. This diverging exercise regulation was confirmed in two independent studies and was also associated with BMI and diabetes in an independent cohort. Thus, the current finding is consistent with the differential responses of different tissues and suggests that body composition may influence the observed individual whole-body metabolic response to exercise training and help explain the observed attenuated whole-body insulin sensitivity after exercise training, even if it has significant effects on the exercising muscle.


Assuntos
Resistência à Insulina , Obesidade , Adulto , Humanos , Obesidade/metabolismo , Músculo Esquelético/metabolismo , Exercício Físico/fisiologia , Gordura Subcutânea/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Expressão Gênica , Tecido Adiposo/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-38581357

RESUMO

Fat is the main component of an adult bone marrow and constitutes the so-called bone marrow adipose tissue (BMAT). Marrow adipocytes, which are the fat cells in the bone marrow, become more abundant with age, and may influence the whole-body metabolism. In osteoporotic patients, the amount of BMAT has an inverse correlation with the amount of bone mass. In people with anorexia nervosa that lose weight after the reduction of peripheral adipose tissues, BMAT expands. Although bone marrow adipocytes are increasingly recognized as a target for therapy, there is still much to learn about their role in skeletal homeostasis, metabolism, cancer, and regenerative treatments. The Bone Marrow Adiposity Society (BMAS), established in 2017, aims to enhance the understanding of how BMAT relates to bone health, cancer, and systemic metabolism. BMAS is committed to training young scientists and organized the second edition of the BMAS Summer School, held on September 4-6, 2023, as a virtual event.


Assuntos
Medula Óssea , Neoplasias , Humanos , Medula Óssea/metabolismo , Adiposidade , Tecido Adiposo/metabolismo , Instituições Acadêmicas , Neoplasias/metabolismo
4.
Am J Physiol Cell Physiol ; 326(4): C1248-C1261, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38581663

RESUMO

Adipose-derived stem cells (ADSCs) play an important role in the differential capacity for excess energy storage between upper body abdominal (ABD) adipose tissue (AT) and lower body gluteofemoral (GF) AT. We cultured ADSCs from subcutaneous ABD AT and GF AT isolated from eight women with differential body fat distribution and performed single-cell RNA sequencing. Six populations of ADSCs were identified and segregated according to their anatomical origin. The three ADSC subpopulations in GF AT were characterized by strong cholesterol/fatty acid (FA) storage and proliferation signatures. The two ABD subpopulations, differentiated by higher expression of committed preadipocyte marker genes, were set apart by differential expression of extracellular matrix and ribosomal genes. The last population, identified in both depots, was similar to smooth muscle cells and when individually isolated and cultured in vitro they differentiated less than the other subpopulations. This work provides important insight into the use of ADSC as an in vitro model of adipogenesis and suggests that specific subpopulations of GF-ADSCs contribute to the more robust capacity for GF-AT to expand and grow compared with ABD-AT in women.NEW & NOTEWORTHY Identification of distinct subpopulations of adipose-derived stem cells (ADSCs) in upper body abdominal subcutaneous (ABD) and lower body gluteofemoral subcutaneous (GF) adipose tissue depots. In ABD-ADSCs, subpopulations are more committed to adipocyte lineage. GF-ADSC subpopulations are enriched for genes involved in lipids and cholesterol metabolism. Similar depot differences were found in stem cell population identified in freshly isolated stoma vascular fraction. The repertoire of ADSCs subpopulations was different in apple-shaped versus pear-shaped women.


Assuntos
Tecido Adiposo , Gordura Subcutânea , Humanos , Feminino , Tecido Adiposo/metabolismo , Adipócitos/metabolismo , Análise de Sequência de RNA , Colesterol/metabolismo
5.
Zhongguo Zhen Jiu ; 44(3): 333-337, 2024 Mar 12.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38467510

RESUMO

Pancreatic adipose tissue serves as a crucial structural basis for the development of glycolipid metabolic disorders. Understanding the mechanisms underlying pancreatic adipose tissue infiltration and regulatory strategies is essential for early intervention in glycolipid metabolic disorders. Pancreatic adipose tissue functions as a significant medium linking systemic immune metabolism, while the pancreatic vascular system emerges as a novel target for sensing pancreatic immune responses and maintaining the body's energy homeostasis, collectively participating in the development of glycolipid metabolic disorders. Acupuncture possesses potential effects in modulating the interaction between resident macrophages and adipocytes in the pancreas, leading to the reversible reduction of excessive pancreatic adipose accumulation, with its action being vascular-dependent.


Assuntos
Terapia por Acupuntura , Doenças Metabólicas , Humanos , Tecido Adiposo/metabolismo , Adipócitos/metabolismo , Pâncreas , Doenças Metabólicas/terapia , Doenças Metabólicas/metabolismo
6.
Physiol Res ; 73(1): 1-8, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466000

RESUMO

Periovarian adipose tissue (POAT) is a type of gonadal white adipose tissue that surrounds the ovary. POAT is a source of various bioactive molecules, such as adipokines, cytokines, chemokines, growth factors and hormones. Thereby it could influence crucial ovarian functions. Recent findings showed that removal of POAT affects folliculogenesis and steroidogenesis in the ovary. Furthermore, changes in the morphology and function of POAT were observed in women during menopause or polycystic ovary syndrome. Although the relationship between the body's energy status and fertility in females is generally well known, the contribution of POAT remains still elusive. Therefore, the objective of this review is summarizing the actual state of knowledge about POAT function in physiological and pathological processes within the ovary.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/metabolismo , Tecido Adiposo/metabolismo , Fertilidade , Adipocinas
7.
Nutrients ; 16(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474830

RESUMO

Obesity is defined as excess adipose tissue; however, commonly used methods may under-detect adiposity in adolescents. This study compared the performance of body mass index percentile (BMI%) and relative body mass index (RBMI) in identifying excess body fat percentage (BF%) and estimated RBMI cut points to better stratify severity of adiposity. In 567 adolescents ages 11-19 year, BF% measured by DXA was used to compare BMI% and RBMI performance at different degrees of adiposity. RBMI cut points for adiposity detection were derived via ROC curve analysis. BF% was strongly correlated with BMI% (r = 0.889, p < 0.001) and RBMI (r = 0.901, p < 0.001). However, RBMI exhibited less dispersion and better discriminated the relationship with BF% independent of age, race, and gender. Both BMI% and RBMI performed similarly for detecting high BF% (≥25 BF% in males; ≥30 BF% in females). Nonetheless, the relationship of BMI% with BF% was diminished among leaner adolescents. RBMI detected overweight in 21.3% more females and 14.2% more males. RBMI improved the detection of excess adiposity in individuals otherwise classified as having normal weight or overweight by BMI%. RBMI is a valuable and accessible tool for earlier detection, intervention, and effective follow-up of excess adiposity in youth at higher risk for complications.


Assuntos
Adiposidade , Sobrepeso , Masculino , Feminino , Adolescente , Humanos , Índice de Massa Corporal , Sobrepeso/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Absorciometria de Fóton , Composição Corporal
8.
Methods Mol Biol ; 2783: 235-262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478237

RESUMO

Advances in technology and automation over the past several decades have made it feasible to perform high-throughput compound screening with cell spheroids, a valuable approach for drug discovery. It is entirely feasible to generate multiple 384-well plates containing adipose spheroids from cryopreserved, single-donor, adipose stem cells, thus incorporating genetic diversity into the discovery stages of research. In this protocol, we describe our method for isolating primary human adipose stem cells and synthesizing cell spheroids comprised of mature adipocytes and stromal cells. Also included are representative outcome measurements useful for characterizing adipocyte metabolism and health. Wherever possible, we describe technologies that can be used to automate characterization and increase throughput.


Assuntos
Adipócitos , Tecido Adiposo , Humanos , Tecido Adiposo/metabolismo , Adipócitos/metabolismo , Esferoides Celulares , Células Estromais , Obesidade/metabolismo , Células-Tronco/metabolismo , Diferenciação Celular
9.
Methods Mol Biol ; 2783: 279-285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478240

RESUMO

White adipose tissue (WAT) plays a crucial endocrine organ that regulates blood glucose and lipid levels, satiety, and inflammation. Before the described technique, primary white adipocytes could not be stably cultured in vitro. The lack of a reliable primary culture model impeded research in WAT metabolism and drug development. We have developed a novel technique for WAT primary culture called "sandwiched white adipose tissue" (SWAT). SWAT overcomes the natural buoyancy of adipocytes by sandwiching minced WAT between sheets of adipose-derived stromal cells. The resulting constructs are viable for at least 8 weeks in culture. SWAT maintains the intact extracellular matrix, cell-to-cell contacts, and physical pressures of in vivo WAT conditions; additionally, SWAT maintains a robust transcriptional profile, sensitivity to exogenous chemical signaling, and whole tissue function. SWAT represents a simple, reproducible, and effective method of primary adipose culture. Potentially, it is a broadly applicable platform for research in WAT physiology, pathophysiology, metabolism, and pharmaceutical development.


Assuntos
Tecido Adiposo Branco , Obesidade , Humanos , Obesidade/metabolismo , Adipócitos , Transdução de Sinais , Tecido Adiposo/metabolismo
10.
Methods Mol Biol ; 2783: 335-347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478245

RESUMO

Bioenergetic and biosynthetic processes are key indicators regulating adipose-derived stromal/stem cell (ADSC) function, health, and differentiation. A common method used to metabolically profile cells is the Seahorse XF Analyzer. This live-cell assay can be used to define key metabolic pathways, including glycolysis and oxidative phosphorylation. Here, we share optimized protocols to characterize metabolism of ADSCs under basal conditions and provide insight into further assays defining metabolic changes and/or dependency during ADSC differentiation.


Assuntos
Smegmamorpha , Animais , Smegmamorpha/metabolismo , Adipócitos , Metabolismo Energético , Fosforilação Oxidativa , Glicólise , Tecido Adiposo/metabolismo
11.
Clin Sci (Lond) ; 138(6): 371-385, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38469619

RESUMO

Browning of white adipose tissue is hallmarked by increased mitochondrial density and metabolic improvements. However, it remains largely unknown how mitochondrial turnover and quality control are regulated during adipose browning. In the present study, we found that mice lacking adipocyte FoxO1, a transcription factor that regulates autophagy, adopted an alternate mechanism of mitophagy to maintain mitochondrial turnover and quality control during adipose browning. Post-developmental deletion of adipocyte FoxO1 (adO1KO) suppressed Bnip3 but activated Fundc1/Drp1/OPA1 cascade, concurrent with up-regulation of Atg7 and CTSL. In addition, mitochondrial biogenesis was stimulated via the Pgc1α/Tfam pathway in adO1KO mice. These changes were associated with enhanced mitochondrial homeostasis and metabolic health (e.g., improved glucose tolerance and insulin sensitivity). By contrast, silencing Fundc1 or Pgc1α reversed the changes induced by silencing FoxO1, which impaired mitochondrial quality control and function. Ablation of Atg7 suppressed mitochondrial turnover and function, causing metabolic disorder (e.g., impaired glucose tolerance and insulin sensitivity), regardless of elevated markers of adipose browning. Consistently, suppression of autophagy via CTSL by high-fat diet was associated with a reversal of adO1KO-induced benefits. Our data reveal a unique role of FoxO1 in coordinating mitophagy receptors (Bnip3 and Fundc1) for a fine-tuned mitochondrial turnover and quality control, underscoring autophagic clearance of mitochondria as a prerequisite for healthy browning of adipose tissue.


Assuntos
Resistência à Insulina , Animais , Camundongos , Tecido Adiposo/metabolismo , Tecido Adiposo Marrom/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Obesidade/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
12.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473844

RESUMO

Nicotinamide mononucleotide (NMN) has emerged as a promising therapeutic intervention for age-related disorders, including type 2 diabetes. In this study, we confirmed the previously observed effects of NMN treatment on glucose uptake and investigated its underlying mechanisms in various tissues and cell lines. Through the most comprehensive proteomic analysis to date, we discovered a series of novel organ-specific effects responsible for glucose uptake as measured by the IPGTT: adipose tissue growing (suggested by increased protein synthesis and degradation and mTOR proliferation signaling upregulation). Notably, we observed the upregulation of thermogenic UCP1, promoting enhanced glucose conversion to heat in intermuscular adipose tissue while showing a surprising repressive effect on mitochondrial biogenesis in muscle and the brain. Additionally, liver and muscle cells displayed a unique response, characterized by spliceosome downregulation and concurrent upregulation of chaperones, proteasomes, and ribosomes, leading to mildly impaired and energy-inefficient protein synthesis machinery. Furthermore, our findings revealed remarkable metabolic rewiring in the brain. This involved increased production of ketone bodies, downregulation of mitochondrial OXPHOS and TCA cycle components, as well as the induction of well-known fasting-associated effects. Collectively, our data elucidate the multifaceted nature of NMN action, highlighting its organ-specific effects and their role in improving glucose uptake. These findings deepen our understanding of NMN's therapeutic potential and pave the way for novel strategies in managing metabolic disorders.


Assuntos
Diabetes Mellitus Tipo 2 , Mononucleotídeo de Nicotinamida , Humanos , Mononucleotídeo de Nicotinamida/metabolismo , Biogênese de Organelas , Proteômica , Tecido Adiposo/metabolismo , Glucose , NAD/metabolismo
13.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473961

RESUMO

Obesity, a complex disorder with rising global prevalence, is a chronic, inflammatory, and multifactorial disease and it is characterized by excessive adipose tissue accumulation and associated comorbidities. Adipose tissue (AT) is an extremely diverse organ. The composition, structure, and functionality of AT are significantly influenced by characteristics specific to everyone, in addition to the variability connected to various tissue types and its location-related heterogeneity. Recent investigation has shed light on the intricate relationship between bone marrow stem cells and obesity, revealing potential mechanisms that contribute to the development and consequences of this condition. Mesenchymal stem cells within the bone marrow, known for their multipotent differentiation capabilities, play a pivotal role in adipogenesis, the process of fat cell formation. In the context of obesity, alterations in the bone marrow microenvironment may influence the differentiation of mesenchymal stem cells towards adipocytes, impacting overall fat storage and metabolic balance. Moreover, bone marrow's role as a crucial component of the immune system adds another layer of complexity to the obesity-bone marrow interplay. This narrative review summarizes the current research findings on the connection between bone marrow stem cells and obesity, highlighting the multifaceted roles of bone marrow in adipogenesis and inflammation.


Assuntos
Adipócitos , Tecido Adiposo , Humanos , Tecido Adiposo/metabolismo , Diferenciação Celular , Adipócitos/metabolismo , Adipogenia , Obesidade/metabolismo , Inflamação/metabolismo , Células da Medula Óssea
14.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474155

RESUMO

Since the emergence of coronavirus disease-19 (COVID-19) in 2019, it has been crucial to investigate the causes of severe cases, particularly the higher rates of hospitalization and mortality in individuals with obesity. Previous findings suggest that adipocytes may play a role in adverse COVID-19 outcomes in people with obesity. The impact of COVID-19 vaccination and infection on adipose tissue (AT) is currently unclear. We therefore analyzed 27 paired biopsies of visceral and subcutaneous AT from donors of the Leipzig Obesity BioBank that have been categorized into three groups (1: no infection/no vaccination; 2: no infection but vaccinated; 3: infected and vaccinated) based on COVID-19 antibodies to spike (indicating vaccination) and/or nucleocapsid proteins. We provide additional insights into the impact of COVID-19 on AT biology through a comprehensive histological transcriptome and serum proteome analysis. This study demonstrates that COVID-19 infection is associated with smaller average adipocyte size. The impact of infection on gene expression was significantly more pronounced in subcutaneous than in visceral AT and mainly due to immune system-related processes. Serum proteome analysis revealed the effects of the infection on circulating adiponectin, interleukin 6 (IL-6), and carbonic anhydrase 5A (CA5A), which are all related to obesity and blood glucose abnormalities.


Assuntos
COVID-19 , Humanos , COVID-19/patologia , Vacinas contra COVID-19 , Proteoma , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Vacinação , Anticorpos Antivirais
15.
Int J Mol Sci ; 25(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38474229

RESUMO

The prevalence of metabolic syndrome is increasing globally due to behavioral and environmental changes. There are many therapeutic agents available for the treatment of chronic metabolic diseases, such as obesity and diabetes, but the data on their efficacy and safety are lacking. Through a pilot study by our group, Zingiber officinale rhizomes used as a spice and functional food were selected as an anti-obesity candidate. In this study, steam-processed ginger extract (GGE) was used and we compared its efficacy at alleviating metabolic syndrome-related symptoms with that of conventional ginger extract (GE). Compared with GE, GGE (25-100 µg/mL) had an increased antioxidant capacity and α-glucosidase inhibitory activity in vitro. GGE was better at suppressing the differentiation of 3T3-L1 adipocytes and lipid accumulation in HepG2 cells and promoting glucose utilization in C2C12 cells than GE. In 16-week high-fat-diet (HFD)-fed mice, GGE (100 and 200 mg/kg) improved biochemical profiles, including lipid status and liver function, to a greater extent than GE (200 mg/kg). The supplementation of HFD-fed mice with GGE (200 mg/kg) resulted in the downregulation of SREBP-1c and FAS gene expression in the liver. Collectively, our results indicate that GGE is a promising therapeutic for the treatment of obesity and metabolic syndrome.


Assuntos
Fármacos Antiobesidade , Síndrome Metabólica , Camundongos , Animais , Vapor , Síndrome Metabólica/tratamento farmacológico , Projetos Piloto , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Dieta Hiperlipídica , Fármacos Antiobesidade/farmacologia , Lipídeos/farmacologia , Camundongos Endogâmicos C57BL , Células 3T3-L1 , Adipogenia
16.
Elife ; 132024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470102

RESUMO

Perirenal adipose tissue (PRAT) is a unique visceral depot that contains a mixture of brown and white adipocytes. The origin and plasticity of such cellular heterogeneity remains unknown. Here, we combine single-nucleus RNA sequencing with genetic lineage tracing to reveal the existence of a distinct subpopulation of Ucp1-&Cidea+ adipocytes that arises from brown-to-white conversion during postnatal life in the periureter region of mouse PRAT. Cold exposure restores Ucp1 expression and a thermogenic phenotype in this subpopulation. These cells have a transcriptome that is distinct from subcutaneous beige adipocytes and may represent a unique type of cold-recruitable adipocytes. These results pave the way for studies of PRAT physiology and mechanisms controlling the plasticity of brown/white adipocyte phenotypes.


Assuntos
Adipócitos Bege , Tecido Adiposo , Camundongos , Animais , Tecido Adiposo/metabolismo , Adipócitos Brancos , Adipócitos Marrons/metabolismo , Termogênese/genética , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/fisiologia
17.
Sci Signal ; 17(827): eadp0688, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470956

RESUMO

IgG accumulation in white adipose tissue contributes to aging-associated metabolic dysfunction.


Assuntos
Tecido Adiposo Branco , Envelhecimento , Humanos , Tecido Adiposo Branco/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo
18.
BMC Endocr Disord ; 24(1): 39, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38481206

RESUMO

BACKGROUND: A better understanding of adipose tissue (AT) dysfunction, which includes morphological and functional changes such as adipocyte hypertrophy as well as impaired adipogenesis, lipid storage/mobilization, endocrine and inflammatory responses, is needed in the context of obesity. One dimension of AT dysfunction, secretory adiposopathy, often assessed as a low plasma adiponectin (A)/leptin (L) ratio, is commonly observed in obesity. The aim of this study was to examine markers of AT development and metabolism in 67 women of varying age and adiposity (age: 40-62 years; body mass index, BMI: 17-41 kg/m2) according to levels of adiponectinemia, leptinemia or the plasma A/L ratio. METHODS: Body composition, regional AT distribution and circulating adipokines were determined. Lipolysis was measured from glycerol release in subcutaneous abdominal (SCABD) and omental (OME) adipocytes under basal, isoproterenol-, forskolin (FSK)- and dibutyryl-cyclic AMP (DcAMP)-stimulated conditions. Adipogenesis (C/EBP-α/ß/δ, PPAR-γ2 and SREBP-1c) and lipid metabolism (ß2-ARs, HSL, FABP4, LPL and GLUT4) gene expression (RT-qPCR) was assessed in both fat depots. Participants in the upper versus lower tertile of adiponectin, leptin or the A/L ratio were compared. RESULTS: Basal lipolysis was similar between groups. Women with a low plasma A/L ratio were characterized by higher adiposity and larger SCABD and OME adipocytes (p<0.01) compared to those with a high ratio. In OME adipocytes, women in the low adiponectinemia tertile showed higher isoproterenol-stimulated lipolysis (0.01

Assuntos
Adiponectina , Leptina , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Adiponectina/metabolismo , Leptina/metabolismo , Isoproterenol/metabolismo , Tecido Adiposo/metabolismo , Obesidade/metabolismo
19.
Front Immunol ; 15: 1201439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482013

RESUMO

Introduction: Obesity is associated with chronic low-grade inflammation of adipose tissue (AT) and an increase of AT macrophages (ATMs) that is linked to the onset of type 2 diabetes. We have recently shown that neutralization of interleukin (IL)-6 in obese AT organ cultures inhibits proliferation of ATMs, which occurs preferentially in alternatively activated macrophage phenotype. Methods: In this study, we investigated AT biology and the metabolic phenotype of mice with myeloid cell-specific IL-6Rα deficiency (Il6ra Δmyel) after normal chow and 20 weeks of high-fat diet focusing on AT inflammation, ATM polarization and proliferation. Using organotypical AT culture and bone marrow derived macrophages (BMDMs) of IL-4Rα knockout mice (Il4ra -/-) we studied IL-6 signaling. Results: Obese Il6ra Δmyel mice exhibited no differences in insulin sensitivity or histological markers of AT inflammation. Notably, we found a reduction of ATMs expressing the mannose receptor 1 (CD206), as well as a decrease of the proliferation marker Ki67 in ATMs of Il6ra Δmyel mice. Importantly, organotypical AT culture and BMDM data of Il4ra -/- mice revealed that IL-6 mediates a shift towards the M2 phenotype independent from the IL-6/IL-4Rα axis. Discussion: Our results demonstrate IL-4Rα-independent anti-inflammatory effects of IL-6 on macrophages and the ability of IL-6 to maintain proliferation rates in obese AT.


Assuntos
Diabetes Mellitus Tipo 2 , Interleucina-6 , Camundongos , Animais , Interleucina-6/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Tecido Adiposo/metabolismo , Macrófagos/metabolismo , Inflamação/metabolismo , Camundongos Knockout , Obesidade/metabolismo
20.
Biochem Pharmacol ; 222: 116104, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428826

RESUMO

Adipose tissues (AT) are an important endocrine organ that secretes various functional adipokines, peptides, non-coding RNAs, and acts on AT themselves or other distant tissues or organs through autocrine, paracrine, or endocrine manners. An accumulating body of evidence has suggested that many adipokines play an important role in liver metabolism. Besides the traditional adipokines such as adiponectin and leptin, many novel adipokines have recently been identified to have regulatory effects on the liver. Additionally, AT can produce extracellular vesicles (EVs) that act on peripheral tissues. However, under pathological conditions, such as obesity and diabetes, dysregulation of adipokines is associated with functional changes in AT, which may cause liver diseases. In this review, we focus on the newly discovered adipokines and EVs secreted by AT and highlight their actions on the liver under the context of obesity, nonalcoholic fatty liver diseases (NAFLD), and some other liver diseases. Clarifying the action of adipokines and adipose tissue-derived EVs on the liver would help to identify novel therapeutic targets or biomarkers for metabolic diseases.


Assuntos
Adipocinas , Hepatopatia Gordurosa não Alcoólica , Humanos , Adipocinas/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Adiponectina , Hepatopatia Gordurosa não Alcoólica/metabolismo
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