Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancy

Obesity increases preeclampsia risk. Adipose tissue inflammation may contribute to the clinical syndrome of pre-eclampsia. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in pre-eclampsia and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and preeclampsia (n=13) mothers. Basal and lipopolysaccharide stimulated adipocyte TNFα, IL-6, CCL-2 and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined. In pre-eclampsia only, visceral adipose tissue TNFα release was increased after lipopolysaccharide stimulation (57 [76] vs 81 [97] pg/mL/ug DNA, p=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r=-0.61, p=0.030) in pre-eclampsia. Visceral adipocyte IL-6 release was increased after lipopolysaccharide stimulation in pre-eclampsia only (566 [696] vs 852 [914] pg/mL/ugDNA, p=0.019). Visceral adipocyte CCL-2 basal (67 [61] vs 187 [219] pg/mL/ugDNA, p=0.049) and stimulated (46 [46] vs 224 [271] pg/mL/ugDNA, p=0.003) release was greater than in subcutaneous adipocytes in pre-eclampsia only. In pre-eclampsia, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13-4.14] vs 0.8 [0.00-1.27] TNF / PPIA ratio, p=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] vs 51.0[29.9] CSF1R/PPIA ratio, p=0.011) and activated (cfms+) macrophage count (6.7[2.6] vs 15.2[8.8] % cfms+/adipocyte, p=0.031) were higher in pre-eclampsia than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in pre-eclampsia. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with pre-eclampsia

Cross talk between adipose tissue and placenta in obese and gestational diabetes mellitus pregnancies via exosomes

Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR). Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM). Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body’s major energy reservoir. The role of adipose tissue, however, is not restricted to a “bag of fat.” The adipose tissue is an endocrine organ, secreting various adipokines, enzymes, growth factors, and hormones that take part in glucose and lipid metabolism. In obesity, the greater portion of the adipose tissue comprises fat, and there is increased pro-inflammatory cytokine secretion, macrophage infiltration, and reduced insulin sensitivity. Obesity contributes to systemic IR and its associated metabolic complications. Similar to adipose tissue, the placenta is also an endocrine organ. During pregnancy, the placenta secretes various molecules to maintain pregnancy physiology. In addition, the placenta plays an important role in metabolism and exchange of nutrients between mother and fetus. Inflammation at the placenta may contribute to the severity of maternal IR and her likelihood of developing GDM and may also mediate the adverse consequences of obesity and GDM on the fetus. Interestingly, studies on maternal insulin sensitivity and secretion of placental hormones have not shown a positive correlation between these phenomena. Recently, a great interest in the field of extracellular vesicles (EVs) has been observed in the literature. EVs are produced by a wide range of cells and are present in all biological fluids. EVs are involved in cell-to-cell communication. Recent evidence points to an association between adipose tissue-derived EVs and metabolic syndrome in obesity. In this review, we will discuss the changes in human placenta and adipose tissue in GDM and obesity and summarize the findings regarding the role of adipose tissue and placenta-derived EVs, with an emphasis on exosomes in obesity, and the contribution of obesity to the development of GDM

Gene Expression Signature in Adipose Tissue of Acromegaly Patients.

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly

Omental adipose tissue is a more suitable source of canine Mesenchymal stem cells

Background: Mesenchymal Stem Cells (MSCs) are a promising therapeutic tool in veterinary medicine. Currently the subcutaneous adipose tissue is the leading source of MSCs in dogs. MSCs derived from distinct fat depots have shown dissimilarities in their accessibility and therapeutic potential. The aims of our work were to determine the suitability of omental adipose tissue as a source of MSCs, according to sampling success, cell yield and paracrine properties of isolated cells, and compared to subcutaneous adipose tissue. Results: While sampling success of omental adipose tissue was 100% (14 collections from14 donors) for subcutaneous adipose tissue it was 71% (10 collections from 14 donors). MSCs could be isolated from both sources. Cell yield was significantly higher for omental than for subcutaneous adipose tissue (38 ± 1 vs. 30 ± 1 CFU-F/g tissue, p < 0.0001). No differences were observed between sources regarding cell proliferation potential (73 ± 1 vs. 74 ± 1 CDPL) and cell senescence (at passage 10, both cultures presented enlarged cells with cytoplasmic vacuoles and cellular debris). Omental- and subcutaneous-derived MSCs expressed at the same level bFGF, PDGF, HGF, VEGF, ANG1 and IL-10. Irrespective of the source, isolated MSCs induced proliferation, migration and vascularization of target cells, and inhibited the activation of T lymphocytes. Conclusion: Compared to subcutaneous adipose tissue, omental adipose tissue is a more suitable source of MSCs in dogs. Since it can be procured from donors with any body condition, its collection procedure is always feasible, its cell yield is high and the MSCs isolated from it have desirable differentiation and paracrine potentials.Fil: Bahamondes, Francisca. Universidad de Chile; Chile. Universidad del Desarrollo; ChileFil: Flores, Estefania. Universidad de Chile; ChileFil: Cattaneo, Gino. Universidad de Chile; ChileFil: Bruna, Flavia Alejandra. Universidad del Desarrollo; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Conget, Paulette. Universidad del Desarrollo; Chil

Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity.

Decreased adipose tissue oxygen tension and increased HIF-1α expression can trigger adipose tissue inflammation and dysfunction in obesity. Our current understanding of obesity-associated decreased adipose tissue oxygen tension is mainly focused on changes in oxygen supply and angiogenesis. Here, we demonstrate that increased adipocyte O2 demand, mediated by ANT2 activity, is the dominant cause of adipocyte hypoxia. Deletion of adipocyte Ant2 improves obesity-induced intracellular adipocyte hypoxia by decreasing obesity-induced adipocyte oxygen demand, without effects on mitochondrial number or mass, or oligomycin-sensitive respiration. This led to decreased adipose tissue HIF-1α expression and inflammation with improved glucose tolerance and insulin resistance in both a preventative or therapeutic setting. Our results suggest that ANT2 may be a target for the development of insulin sensitizing drugs and that ANT2 inhibition might have clinical utility

Protective Role of S-Adenosylmethionine Against Fructose-Induced Oxidative Damage in Obesity

Introduction. It has been shown that S-adenosylmethionine (S-AMe) stimulates glutathione synthesis and increases cell resistance to the cytotoxic action of free radicals and pro-inflammatory cytokines. The aim of this study was to determine the effect of S-adenosylmethionine on the oxidative stress in adipose tissue in a model of fructose-induced obesity. Methods. The study was performed on male Wistar rats divided into 3 groups: control, fructose fed (HFD) (35%, 16 weeks), and HFD + S-AMe (20 mg/kg). We examined the changes in the ratio of retroperitoneal adipose tissue weight / body weight; levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the retroperitoneal adipose tissue, and serum levels of GSH and TNF-α. Results. Significant increases in the retroperitoneal adipose tissue, MDA, and serum TNF-α were identified, as well as decreased tissue and serum levels of GSH in rats fed with a high-fructose diet as compared with the control group. In the group fed with HFD and S-AMe, we found significant reduction in the retroperitoneal adipose tissue and decreased levels of MDA and serum TNF-α, as well as increased tissue and serum levels of GSH as compared with the group only on HFD. In conclusion, our results show that fructose-induced obesity causes oxidative stress in hypertrophic visceral adipose tissue. The administration of S-AMe improves the antioxidative protection of adipocytes, and reduces oxidative damage and excessive accumulation of lipids and inflammation

ILC2s chew the fat.

In this issue of JEM, Rana et al. (https://doi.org/10.1084/jem.20190689) report that adipose tissue multipotent stromal cells (MSCs) provide multifaceted support for adipose tissue-resident ILC2s through contact-mediated proliferation and IL-33-mediated stress-induced activation

Extracellular vesicles from adipose tissue - a potential role in obesity and type 2 diabetes?

Adipose tissue plays a key role in the development of insulin resistance and its pathological sequelae such as type 2 diabetes and non-alcoholic fatty liver disease. Dysfunction in the adipose tissue response to storing excess fatty acids as triglyceride can lead to adipose tissue inflammation and spillover of fatty acids from this tissue and accumulation of fatty acids as lipid droplets in ectopic sites such as liver and muscle. Extracellular vesicles (EV) are released from adipocytes and have been proposed to be involved in adipocyte/macrophage crosstalk and to affect insulin signalling and TGFβ expression in liver cells leading to metabolic disease. Furthermore EV produced by adipose tissue-derived mesenchymal stem cells (ADSC) can promote angiogenesis and cancer cell migration and have neuroprotective and neuroregenerative properties. ADSC EV have therapeutic potential in vascular and neurodegenerative disease and may also be used to target specific functional miRNAs to cells. Obesity is associated with an increase in adipose-derived EV which may be related to the metabolic complications of obesity. This review aims to discuss EV produced by adipose tissue and their potential impact on metabolic diseases associated with obesity

Sexual dimorphism of brown adipose tissue function

ObjectiveTo determine whether brown adipose tissue (BAT) activity in school-age children differs between the sexes and to explore the impact of dietary intake, sedentary behavior, and picky/fussy eating.Study designChildren aged 8.5-11.8 years of age (n = 36) underwent infrared thermography to determine the temperature of the skin overlying the main superficial BAT depot in the supraclavicular region before and after 5 minutes of mild cold exposure (single-hand immersion in cool tap water at about 20°C). The relationships between the supraclavicular region temperature and parental reports of food consumption, eating behavior, and inactivity were explored.ResultsThe supraclavicular region temperature was higher in boys (n = 16) at baseline, and after cold exposure. Boys displayed a greater thermogenic response to cold. Strong negative correlations were observed between the supraclavicular region temperature and body mass index percentile, and differences in supraclavicular region temperature between girls and boys persisted after adjustment for body mass index percentile. A negative linear relationship was observed between protein and vegetable intake and supraclavicular region temperature in girls only, but did not persist after adjustment for multiple comparisons. There was no difference in the adjusted supraclavicular region temperature between active or inactive children, or picky and nonpicky eaters.ConclusionsThese findings indicate sexual dimorphism in BAT thermogenic activity and a sex-specific impact of diet. Future studies should aim to quantify the contribution of BAT to childhood energy expenditure, energy imbalance, and any role in the origins of childhood obesity