scholarly journals Lipogenic Potency of Individual Perfluorinated Alkyl Acids (PFAAs) and Persistent Organic Pollutant (POP) Mixtures at Human Blood-Based Exposure Levels on Adipogenesis in 3T3-L1 Cells

2021 ◽  
Author(s):  
Y. Xie ◽  
H. F. Berntsen ◽  
K. E. Zimmer ◽  
E. Ropstad ◽  
S. Verhaegen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Human Blood ◽  
Lipid Accumulation ◽  
Human Exposure ◽  
Metabolic Disorders ◽  
Real Life ◽  
Metabolic Effects ◽  
Blood Levels ◽  
Total Mixture ◽  
Exposure Levels

AbstractIn recent decades, the incidence of metabolic disorders has increased internationally. This increase has been linked to exposure to persistent organic pollutants (POPs), but little is known about the metabolic effects of realistic human exposure mixtures at relevant concentrations. In this study we tested if POPs, representing real-life exposure profiles and concentrations, were able to disrupt development and functions of adipose tissue in a direct way. The lipogenic potency of a POP mixture modelled on levels found in human blood as detected in the Scandinavian population was assessed. The Total mixture comprises 29 compounds divided over three groups: chlorinated (Cl), brominated (Br) and perfluorinated compounds (PFAA). Individual PFAA chemicals, the Total mixture and sub-mixtures (Cl, Br, PFAA, Cl + Br, Cl + PFAA and Br + PFAA) at five (× 1/10, × 1, × 50, × 100 and × 500) human blood levels were tested in an optimized high content analysis (HCA) 3T3-L1 adipogenesis assay. All exposures promoted adipocyte formation in 3T3-L1 cells at concentrations equivalent to × 1/10 human blood levels. PFAAs promoted lipid accumulation in 3T3-L1 cells at 33.6 pM (PFUnDA) and 390,460 pM (PFHxS). The Total mixture, and the Cl, PFAA, Cl + Br and Cl + PFAA sub-mixtures, started to promote lipid accumulation at × 1/10 human blood levels. This in vitro bioassay study assessed the adipogenic effects of POP mixtures modelled on real-life human exposure levels. The findings highlight that such exposures may alter adipose tissue development and function, thus potentially playing a role in the globally increasing escalation of metabolic disorders.

scholarly journals Lipogenic Potency of Individual Perfluorinated Alkyl Acids (PFAAs) and Persistent Organic Pollutant (POP) Mixtures at Human Blood-Based Exposure Levels on Adipogenesis in 3T3-L1 Cells

2021 ◽  
Author(s):  
Yuling Xie ◽  
H.F. Berntsen ◽  
K.E. Zimmer ◽  
E. Ropstad ◽  
S. Verhaegen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Human Blood ◽  
Lipid Accumulation ◽  
Human Exposure ◽  
Metabolic Disorders ◽  
Real Life ◽  
Metabolic Effects ◽  
Total Mixture ◽  
Exposure Levels ◽  
Perfluorinated Alkyl Acids

Abstract Background In recent decades, the incidence of metabolic disorders has increased internationally. This increase has been linked to exposure to persistent organic pollutants (POPs) but little is known about the metabolic effects of realistic human exposure mixtures at relevant concentrations. Objectives In this study we tested if POPs, representing real life exposure profiles and concentrations, were able to disrupt development and functions of adipose tissue in a direct way. Methods The lipogenic potency of a POP mixture modelled on levels found in human blood as detected in the Scandinavian population was assessed. The Total mixture comprises 29 compounds divided over three groups: chlorinated (Cl), brominated (Br), and perfluorinated compounds (PFAA). Individual PFAA chemicals, the Total mixture, and sub-mixtures (Cl, Br, PFAA, Cl + Br, Cl + PFAA, and Br + PFAA) at five (× 1/10, × 1, × 50, × 100, and × 500) human blood levels were tested in an optimised high content analysis (HCA) 3T3-L1 adipogenesis assay. Results Individual PFAAs; perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) promoted lipid accumulation in 3T3-L1 cells. The Total mixture, and the Cl, PFAA, Cl + Br, and Cl + PFAA sub-mixtures, promoted adipogenic differentiation and lipid accumulation. Increased lipid accumulation promoted adipose tissue expansion. Conclusions To the authors knowledge, this is the first in vitro bioassay study assessing the adipogenic effects of POP mixtures modelled on real-life human exposure levels. The findings highlight that such exposures may alter adipose tissue development and function, thus potentially playing a role in the globally increasing escalation of metabolic disorders.

scholarly journals Mice lacking PLAP-1/asporin counteracts high fat diet-induced metabolic disorder and alveolar bone loss by controlling adipose tissue expansion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiromi Sakashita ◽  
Satoru Yamada ◽  
Masaki Kinoshita ◽  
Tetsuhiro Kajikawa ◽  
Tomoaki Iwayama ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Periodontal Disease ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Periodontal Ligament ◽  
Metabolic Disorders ◽  
Alveolar Bone ◽  
High Fat ◽  
Knock Out ◽  
Knock Out Mice

AbstractAdipose tissue fibrosis with chronic inflammation is a hallmark of obesity-related metabolic disorders, and the role of proteoglycans in developing adipose tissue fibrosis is of interest. Periodontal disease is associated with obesity; however, the underlying molecular mechanisms remain unclear. Here we investigated the roles of periodontal ligament associated protein-1 (PLAP-1)/asporin, a proteoglycan preferentially and highly expressed in the periodontal ligament, in obesity-related adipose tissue dysfunction and adipocyte differentiation. It was found that PLAP-1 is also highly expressed in white adipose tissues. Plap-1 knock-out mice counteracted obesity and alveolar bone resorption induced by a high-fat diet. Plap-1 knock-down in 3T3-L1 cells resulted in less lipid accumulation, and recombinant PLAP-1 enhanced lipid accumulation in 3T3-L1 cells. In addition, it was found that primary preadipocytes isolated from Plap-1 knock-out mice showed lesser lipid accumulation than the wild-type (WT) mice. Furthermore, the stromal vascular fraction of Plap-1 knock-out mice showed different extracellular matrix gene expression patterns compared to WT. These findings demonstrate that PLAP-1 enhances adipogenesis and could be a key molecule in understanding the association between periodontal disease and obesity-related metabolic disorders.

scholarly journals Beneficial Role of HO-1-SIRT1 Axis in Attenuating Angiotensin II-Induced Adipocyte Dysfunction

2019 ◽  
Vol 20 (13) ◽  
pp. 3205 ◽  
Author(s):  
Hari Vishal Lakhani ◽  
Mishghan Zehra ◽  
Sneha S. Pillai ◽  
Nitin Puri ◽  
Joseph I. Shapiro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Subsequent Treatment ◽  
Sirtuin 1 ◽  
Metabolic Effects ◽  
Heme Oxygenase 1

Background: Angiotensin II (Ang II), released by the renin–angiotensin–aldosterone system (RAAS), contributes to the modulatory role of the RAAS in adipose tissue dysfunction. Investigators have shown that inhibition of AngII improved adipose tissue function and insulin resistance in mice with metabolic syndrome. Heme Oxygenase-1 (HO-1), a potent antioxidant, has been demonstrated to improve oxidative stress and adipocyte phenotype. Molecular effects of high oxidative stress include suppression of sirtuin-1 (SIRT1), which is amenable to redox manipulations. The mechanisms involved, however, in these metabolic effects of the RAAS remain incompletely understood. Hypothesis: We hypothesize that AngII-induced oxidative stress has the potential to suppress adipocyte SIRT1 via down regulation of HO-1. This effect of AngII will, in turn, upregulate mineralocorticoid receptor (MR). The induction of HO-1 will rescue SIRT1, hence improving oxidative stress and adipocyte phenotype. Methods and Results: We examined the effect of AngII on lipid accumulation, oxidative stress, and inflammatory cytokines in mouse pre-adipocytes in the presence and absence of cobalt protoporphyrin (CoPP), HO-1 inducer, tin mesoporphyrin (SnMP), and HO-1 inhibitor. Our results show that treatment of mouse pre-adipocytes with AngII increased lipid accumulation, superoxide levels, inflammatory cytokine levels, interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), and adiponectin levels. This effect was attenuated by HO-1 induction, which was further reversed by SnMP, suggesting HO-1 mediated improvement in adipocyte phenotype. AngII-treated pre-adipocytes also showed upregulated levels of MR and suppressed SIRT1 that was rescued by HO-1. Subsequent treatment with CoPP and SIRT1 siRNA in mouse pre-adipocytes increased lipid accumulation and fatty acid synthase (FAS) levels, suggesting that beneficial effects of HO-1 are mediated via SIRT1. Conclusion: Our study demonstrates for the first time that HO-1 has the ability to restore cellular redox, rescue SIRT1, and prevent AngII-induced impaired effects on adipocytes and the systemic metabolic profile.

scholarly journals Justification of the need to create a new classification of obesity

2021 ◽  
Author(s):  
С.В. Миклишанская ◽  
Е.А. Золозова ◽  
А.А. Орловский ◽  
Г.В. Шлевкова ◽  
Н.А. Мазур
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Metabolic Disorders ◽  
Blood Levels ◽  
Bioimpedance Analysis ◽  
New Classification ◽  
Clinical Method ◽  
The Metabolic Syndrome ◽  
Visceral Adipose

Результаты многочисленных исследований, проведенных в последние десятилетия, показали, что наибольшее значение в определении риска развития заболеваний и смерти на индивидуальном уровне имеет накопление висцеральной жировой ткани, сопряженное с развитием метаболических нарушений и местным влиянием при ее накоплении во внутренних органах. Биоимпедансный анализ служит простым и доступным в широкой клинической практике способом определения избыточного содержания висцеральной жировой ткани, позволяя тем самым выявлять пациентов с ожирением и высоким риском развития сердечно-сосудистых осложнений даже в рамках первой встречи с врачом. Результаты определения висцеральной жировой ткани с помощью биоимпедансного анализа сопоставимы с данными, полученными при КТ и МРТ. По нашим наблюдениям, проведенным на 154 больных с различными сердечно-сосудистыми заболеваниями, содержание висцеральной жировой ткани, составляющее 14% и более по данным биоимпедансного анализа, сочеталось с нарушениями, характерными для метаболического синдрома. При этом нарастание индекса массы тела от 1-й до 3-й степени никак не отражало степень тяжести метаболических нарушений. Достоверных отличий по содержанию висцеральной жировой ткани и уровням содержания в крови триглицеридов, глюкозы и липопротеинов высокой плотности у больных с разными степенями ожирения также выявлено не было. На сегодняшний день очевидно, что ожирение, определяемое с помощью индекса массы тела, является очень гетерогенным и его отрицательная роль в развитии заболеваний выявляется только при наблюдении за очень большими группами населения. Данные исследований о значении висцеральной жировой ткани и ее связи с факторами риска развития сердечно-сосудистых заболеваний свидетельствуют о необходимости создания новой классификации ожирения. Проект для ее обсуждения приводится в нашей статье. The results of numerous studies conducted over the past decades have shown that the greatest importance in determining the risk of disease and death at the individual level is the accumulation of visceral adipose tissue, associated with the development of metabolic disorders and local influence when it accumulates in the internal organs. Bioimpedance analysis is a simple and widely available clinical method for determining the excess content of visceral adipose tissue, thereby allowing you to identify patients with obesity and a high risk of developing cardiovascular complications, even in the first meeting with a doctor. The results of the determination of visceral adipose tissue by bioimpedance analysis are comparable with the data obtained by CT and MRI. According to our observations conducted on 154 patients with various cardiovascular diseases, the content of visceral adipose tissue , which is 14% or more according to bioimpedance analysis, was combined with disorders characteristic of the metabolic syndrome. At the same time, the increase in BMI from the 1st to the 3rd degree did not reflect the severity of metabolic disorders. There were no significant differences in the content of visceral adipose tissue and blood levels of triglycerides, glucose, and HDL-C in patients with different degrees of obesity. To date, it is obvious that obesity, determined by BMI, is very heterogeneous and its negative role in the development of diseases is revealed only when observing very large groups of the population. Research data on the importance of visceral adipose tissue and its association with risk factors for cardiovascular disease suggest the need for a new classification of obesity. We present a draft for discussing the new classification of obesity in our article.

Neck adipose tissue – tying ties in metabolic disorders

2018 ◽  
Vol 33 (2) ◽  
Author(s):  
Vlatka Pandzic Jaksic ◽  
Danijela Grizelj ◽  
Ana Livun ◽  
Drago Boscic ◽  
Marko Ajduk ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Metabolic Effects ◽  
Upper Body ◽  
Perivascular Adipose Tissue ◽  
Vascular Regulation ◽  
Metabolic Role ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Human Adults

AbstractUpper body adipose tissue accumulation has been associated with clustering of metabolic disorders and increased cardiovascular risk. Neck circumference (NC) indicated that subcutaneous adipose tissue (SAT) in that region is an independent pathogenic depot that might account for the additional risk missed by visceral adipose tissue (VAT). Neck adipose tissue (NAT) is not only one more ectopic depot but has several particular features that might modulate its metabolic role. Besides a controversial impact on obstructive apnea syndrome, neck fat encompasses carotid arteries as an important perivascular adipose tissue (PVAT) depot. With dysfunctional changes in obesity, physiologic vascular regulation is lost and inflammatory signals accelerate atherogenesis. Unexpected was the discovery of brown and beige adipocytes in the neck of human adults. When stimulated, brown adipose tissue (BAT) dissipates energy through thermogenesis and it is associated with other favorable metabolic effects. Moreover, the neck is the region where the browning mechanism was disclosed. With this unique plastic nature, NAT revealed multiple ties, challenging dynamics and potential new therapeutic targets that might have significant implications on metabolic outcomes and vascular risk.

scholarly journals Human-Based Exposure Levels of Perfluoroalkyl Acids May Induce Harmful Effects to Health by Disrupting Major Components of Androgen Receptor Signalling In Vitro

2019 ◽  
Vol 12 (3) ◽  
pp. 527-538
Author(s):  
J. McComb ◽  
I. G. Mills ◽  
Hanne Friis Berntsen ◽  
E. Ropstad ◽  
S. Verhaegen ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Health Effects ◽  
Human Blood ◽  
Human Exposure ◽  
Perfluoroalkyl Acids ◽  
Disruptive Effect ◽  
Receptor Signalling ◽  
Gene Assay ◽  
Exposure Levels

AbstractPerfluoroalkyl acids (PFAAs) are detectable in human blood. PFAA exposure may contribute to androgen receptor (AR)-related health effects such as prostate cancer (PCa). In Norway and Sweden, exposures to PFAAs and PCa are very real concerns. In vitro studies conventionally do not investigate PFAA-induced AR disruption at human blood-based concentrations, thus limiting application to human health. We aim to determine the endocrine disrupting activity of PFAAs based upon human exposure levels, on AR transactivation and translocation. PFAAs (PFOS, PFOA, PFNA, PFDA, PFHxS, and PFUnDA) were tested at concentrations ranging from 1/10 × to 500 × relative to human blood based upon the exposure levels observed in a Scandinavian population. Translocation was measured by high content analysis (HCA) and transactivation was measured by reporter gene assay (RGA). No agonist activity (translocation or transactivation) was detected for any PFAAs. In the presence of testosterone, AR translocation increased following exposure to PFOS 1/10 × and 100 ×, PFOA 1/10 ×, and PFNA 1 × and 500 × (P < 0.05). In the presence of testosterone, PFOS 500 × antagonised AR transactivation, whereas PFDA 500 × increased AR transactivation (P < 0.05). PFAAs may contribute to AR-related adverse health effects such as PCa. PFAAs can disrupt AR signalling via two major components: translocation and transactivation. PFAAs which disrupt one signalling component do not necessarily disrupt both. Therefore, to fully investigate the disruptive effect of human exposure-based contaminants on AR signalling, it is imperative to analyse multiple molecular components as not all compounds induce a disruptive effect at the same level of receptor signalling.

scholarly journals Adipose Tissue Immunomodulation and Treg/Th17 Imbalance in the Impaired Glucose Metabolism of Children with Obesity

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 554
Author(s):  
Stefania Croce ◽  
Maria Antonietta Avanzini ◽  
Corrado Regalbuto ◽  
Erika Cordaro ◽  
Federica Vinci ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Th17 Cells ◽  
Metabolic Disorders ◽  
Potential Role ◽  
Immune Monitoring ◽  
Metabolic Dysfunction ◽  
Impaired Glucose Metabolism ◽  
T Cell Infiltration

In the last few decades, obesity has increased dramatically in pediatric patients. Obesity is a chronic disease correlated with systemic inflammation, characterized by the presence of CD4 and CD8 T cell infiltration and modified immune response, which contributes to the development of obesity related diseases and metabolic disorders, including impaired glucose metabolism. In particular, Treg and Th17 cells are dynamically balanced under healthy conditions, but imbalance occurs in inflammatory and pathological states, such as obesity. Some studies demonstrated that peripheral Treg and Th17 cells exhibit increased imbalance with worsening of glucose metabolic dysfunction, already in children with obesity. In this review, we considered the role of adipose tissue immunomodulation and the potential role played by Treg/T17 imbalance on the impaired glucose metabolism in pediatric obesity. In the patient care, immune monitoring could play an important role to define preventive strategies of pediatric metabolic disease treatments.

scholarly journals Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

2021 ◽  
Vol 10 (4) ◽  
pp. 835
Author(s):  
Manoja P. Herath ◽  
Jeffrey M. Beckett ◽  
Andrew P. Hills ◽  
Nuala M. Byrne ◽  
Kiran D. K. Ahuja
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fat Mass ◽  
Metabolic Disorders ◽  
Later Life ◽  
Therapeutic Interventions ◽  
Increased Risk ◽  
The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

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