| 51. |
- Weiskopf, Sarah R., et al.
(författare)
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A Conceptual Framework to Integrate Biodiversity, Ecosystem Function, and Ecosystem Service Models
- 2022
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 72:11, s. 1062-1073
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Tidskriftsartikel (refereegranskat)abstract
- Global biodiversity and ecosystem service models typically operate independently. Ecosystem service projections may therefore be overly optimistic because they do not always account for the role of biodiversity in maintaining ecological functions. We review models used in recent global model intercomparison projects and develop a novel model integration framework to more fully account for the role of biodiversity in ecosystem function, a key gap for linking biodiversity changes to ecosystem services. We propose two integration pathways. The first uses empirical data on biodiversity–ecosystem function relationships to bridge biodiversity and ecosystem function models and could currently be implemented globally for systems and taxa with sufficient data. We also propose a trait-based approach involving greater incorporation of biodiversity into ecosystem function models. Pursuing both approaches will provide greater insight into biodiversity and ecosystem services projections. Integrating biodiversity, ecosystem function, and ecosystem service modeling will enhance policy development to meet global sustainability goals.
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| 52. |
- Weiskopf, Sarah R., et al.
(författare)
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Increasing the uptake of ecological model results in policy decisions to improve biodiversity outcomes
- 2022
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Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152 .- 1873-6726. ; 149
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Tidskriftsartikel (refereegranskat)abstract
- Models help decision-makers anticipate the consequences of policies for ecosystems and people; for instance, improving our ability to represent interactions between human activities and ecological systems is essential to identify pathways to meet the 2030 Sustainable Development Goals. However, use of modeling outputs in decision-making remains uncommon. We share insights from a multidisciplinary National Socio-Environmental Synthesis Center working group on technical, communication, and process-related factors that facilitate or hamper uptake of model results. We emphasize that it is not simply technical model improvements, but active and iterative stakeholder involvement that can lead to more impactful outcomes. In particular, trust-and relationship-building with decision-makers are key for knowledge-based decision making. In this respect, nurturing knowledge exchange on the interpersonal (e.g., through participatory processes) and institutional level (e.g., through science-policy interfaces across scales) represents a promising approach. To this end, we offer a generalized approach for linking modeling and decision-making.
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| 53. |
- Ahmed, Fozia, et al.
(författare)
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ESR2 expression in subcutaneous adipose tissue is related to body fat distribution in women, and knockdown impairs preadipocyte differentiation
- 2022
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Ingår i: Adipocyte. - : Informa UK Limited. - 2162-3945 .- 2162-397X. ; 11:1, s. 434-447
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Tidskriftsartikel (refereegranskat)abstract
- Oestrogen receptor 2 (ESR2) expression has been shown to be higher in subcutaneous adipose tissue (SAT) from postmenopausal compared to premenopausal women. The functional significance of altered ESR2 expression is not fully known. This study investigates the role of ESR2 for adipose tissue lipid and glucose metabolism. SAT biopsies were obtained from 44 female subjects with or without T2D. Gene expression of ESR2 and markers of adipose function and metabolism was assessed. ESR2 knockdown was performed using CRISPR/Cas9 in preadipocytes isolated from SAT of females, and differentiation rate, lipid storage, and glucose uptake were measured. ESR2 expression was inversely correlated with measures of central obesity and expression of some fatty acid oxidation markers, and positively correlated with lipid storage and glucose transport markers. Differentiation was reduced in ESR2 knockdown preadipocytes. This corresponded to reduced expression of markers of differentiation and lipogenesis. Glucose uptake was reduced in knockdown adipocytes. Our results indicate that ESR2 deficiency in women is associated with visceral adiposity and impaired subcutaneous adipocyte differentiation as well as glucose and lipid utilization. High ESR2 expression, as seen after menopause, could be a contributing factor to SAT expansion. This may support a possible target to promote a healthy obesity phenotype.
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| 54. |
- Ahmed, Fozia
(författare)
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Estrogen and its receptors in adipose tissue from women and men : Associations with age, adiposity and type 2 diabetes
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity and its complications, such as insulin resistance and type 2 diabetes (T2D), are leading causes of morbidity and mortality globally. Adipose tissue is important for whole-body homeostasis, functioning as an energy storage reservoir and an endocrine organ. Estrogens mediate their effects through estrogen receptor alpha (ESR1) and beta (ESR2) and contribute to sex and menopause-related differences in body fat distribution. Moreover, estrogens can be produced from androgens in the adipose tissue by the enzyme aromatase. The overall aim of this thesis was to investigate the role of estrogen and estrogen signalling in human adipose tissue and their association with age, adiposity, and insulin resistance. In Paper I, we assessed ESR1 and ESR2 gene expression in subcutaneous adipose tissue (SAT) from pre- and postmenopausal women, and investigated the effects of estradiol on adipocyte glucose uptake. We found that ESR2 gene expression was higher in postmenopausal women than premenopausal women. Moreover, in late, but not pre- or early postmenopausal women, estradiol incubation reduced basal and insulin-stimulated glucose uptake, which corresponded to an increase in ESR2 gene expression levels. The inhibiting effect of estradiol on adipocyte glucose uptake was prevented using an ESR2 antagonist. Subsequently, in Paper II we assessed the role of ESR2 in SAT lipid and glucose metabolism and preadipocyte differentiation. ESR2 expression in SAT was inversely correlated with markers of central adiposity and positively correlated with markers of lipid accumulation. Moreover, ESR2 knockdown impaired subcutaneous preadipocyte differentiation and glucose utilization. In Paper III, we focused on adipocyte lipolysis in women, which is regulated, in part, by catecholamines. OCT3, which mediates catecholamine transport into adipocytes, where they can be degraded, was increased in SAT with age, and higher in postmenopausal women than premenopausal women. Moreover, its expression was negatively associated with markers of insulin resistance and ex vivo lipolysis. Estradiol incubation of SAT downregulated OCT3 gene expression, which may explain lower OCT3 gene expression in premenopausal compared to postmenopausal women. In Paper IV, we focused on the role of aromatase and estradiol in SAT from men. We found that aromatase expression was higher in SAT from men with obesity and T2D compared to subjects without obesity and T2D, respectively, and was positively associated with markers of central obesity and markers of insulin resistance. Contrastingly, ESR1 expression in SAT was lower in men with obesity and T2D compared to subjects without obesity and T2D, respectively, and negatively associated with markers of obesity and insulin resistance. ESR2 expression was higher in SAT from men with T2D compared to men without T2D. Estradiol reduced insulin-stimulated glucose uptake, however, neither testosterone, nor aromatase inhibition, altered adipocyte glucose uptake. In this thesis, we found that estrogen has important metabolic effects in adipose tissue, including regulating lipid accumulation, glucose uptake capacity, and catecholamine transport. Overall, our findings suggest that estrogen and estrogen receptors may have an important role in age-, menopausal- and sex-dependent differences in body fat distribution, and may serve as potential targets for the prevention and treatment obesity and insulin resistance.
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| 55. |
- Ahmed, Fozia, et al.
(författare)
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Increased OCT3 Expression in Adipose Tissue With Aging : Implications for Catecholamine and Lipid Turnover and Insulin Resistance in Women
- 2023
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Ingår i: Endocrinology. - : Oxford University Press. - 0013-7227 .- 1945-7170. ; 165:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Catecholamine-stimulated lipolysis is reduced with aging, which may promote adiposity and insulin resistance. Organic cation transporter 3 (OCT3), which is inhibited by estradiol (E2), mediates catecholamine transport into adipocytes for degradation, thus decreasing lipolysis. In this study, we investigated the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and markers of insulin resistance in women.Methods SAT biopsies were obtained from 66 women with (19) or without (47) type 2 diabetes (age 22-76 years, 20.0-40.1 kg/m2). OCT3 mRNA and protein levels were measured for group comparisons and correlation analysis. SAT was incubated with E2 and OCT3 mRNA levels were measured. Associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed.Results OCT3 mRNA and protein levels in SAT increased with aging. SAT from postmenopausal women had higher levels of OCT3 than premenopausal women, and there was a dose-dependent reduction in OCT3 mRNA levels in SAT treated with E2. OCT3 mRNA levels were negatively associated with markers of insulin resistance, and ex vivo lipolysis. OCT3 SNPs were associated with BMI, waist to hip ratio, and circulating lipids (eg, triglycerides).Conclusion OCT3 mRNA and protein levels in SAT increased with aging, and mRNA levels were negatively associated with markers of insulin resistance. E2 incubation downregulated OCT3 mRNA levels, which may explain lower OCT3 mRNA in premenopausal vs postmenopausal women. High OCT3 protein levels in adipose tissue may result in increased catecholamine degradation, and this can contribute to the reduction in lipolysis observed in women with aging.
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| 56. |
- Ahmed, Fozia, et al.
(författare)
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The effects of bisphenol A and bisphenol S on adipokine expression and glucose metabolism in human adipose tissue
- 2020
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 445
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe environmental endocrine disruptors, bisphenol A (BPA) and bisphenol S (BPS) are associated with the development of type 2 diabetes. We aim to study the effects of BPA or BPS exposure on adipokine expression in human adipose tissue and on adipocyte glucose uptake.MethodsHuman subcutaneous adipose tissue was treated for 24 or 72 h with environmentally-relevant and supraphysiological concentrations of BPA or BPS (1–104 nM). Following exposure, gene expression of proinflammatory cytokines, adipokines, and estrogen receptors was measured in adipose tissue. Glucose uptake and the insulin signalling pathway were analyzed in isolated adipocytes following adipose tissue culture with BPA for 24 h.ResultsAdipose tissue treated with BPA for 24 h had reduced expression of the proinflammatory genes (IL6, IL1B, TNFA) and adipokines (ADIPOQ, FABP4). BPA and BPS had no effect on the expression of other proinflammatory genes (IL33), adipokines (LEP), or receptors (ESR1, ESR2) after 72-h exposure. Adipose tissue treated with environmentally-relevant concentrations of BPA for 24 h had reduced insulin-stimulated glucose uptake, without altered gene and protein levels of key insulin signalling pathway markers.ConclusionsWe found that human adipose tissue treated with environmentally-relevant concentrations of BPA for 24 h, but not BPS, reduced expression of proinflammatory genes and adipokines. Furthermore, BPA reduced glucose uptake in adipocytes independently of insulin signalling. Such mechanisms can contribute to the development of insulin resistance associated with BPA exposure.
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| 57. |
- Almby, Kristina E., et al.
(författare)
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Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277
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Tidskriftsartikel (refereegranskat)abstract
- While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
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| 58. |
- Almby, Kristina E., et al.
(författare)
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Time course of metabolic, neuroendocrine, and adipose effects during 2 years of follow-up after gastric bypass in patients with type 2 diabetes
- 2021
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 106:10, s. E4049-E4061
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Tidskriftsartikel (refereegranskat)abstract
- Context: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood.Objective: Integrated assessment of neuroendocrine and metabolic changes over time inT2D patients undergoing RYGB.Design and Setting: Follow-up of single-center randomized study.Patients: Thirteen patients with obesity andT2D compared to 22 healthy subjects.Interventions: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB.Results: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P < 0.001). At 4 weeks, morning cortisol (P < 0.05) and adrenocorticotropin (P = 0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P < 0.05) and peaked at 24 weeks (P < 0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P < 0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P < 0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P < 0.01).Conclusions: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls).Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.
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| 59. |
- Barbosa, Pedro, et al.
(författare)
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Bariatric Surgery Induces Alterations in the Immune Profile of Peripheral Blood T Cells
- 2024
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Low-grade inflammation is closely linked to obesity and obesity-related comorbidities; therefore, immune cells have become an important topic in obesity research. Here, we performed a deep phenotypic characterization of circulating T cells in people with obesity, using flow cytometry. Forty-one individuals with obesity (OB) and clinical criteria for bariatric surgery were enrolled in this study. We identified and quantified 44 different circulating T cell subsets and assessed their activation status and the expression of immune-checkpoint molecules, immediately before (T1) and 7-18 months after (T2) the bariatric surgery. Twelve age- and sex-matched healthy individuals (nOB) were also recruited. The OB participants showed higher leukocyte counts and a higher percentage of neutrophils. The percentage of circulating Th1 cells were negatively correlated to HbA1c and insulin levels. OB Th1 cells displayed a higher activation status and lower PD-1 expression. The percentage of Th17 and Th1/17 cells were increased in OB, whereas the CD4+ Tregs' percentage was decreased. Interestingly, a higher proportion of OB CD4+ Tregs were polarized toward Th1- and Th1/17-like cells and expressed higher levels of CCR5. Bariatric surgery induced the recovery of CD4+ Treg cell levels and the expansion and activation of Tfh and B cells. Our results show alterations in the distribution and phenotype of circulating T cells from OB people, including activation markers and immune-checkpoint proteins, demonstrating that different metabolic profiles are associated to distinct immune profiles, and both are modulated by bariatric surgery.
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| 60. |
- Barbosa, Pedro, et al.
(författare)
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CD8+Treg cells play a role in the obesity-associated insulin resistance
- 2024
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Ingår i: Life Sciences. - : Elsevier. - 0024-3205 .- 1879-0631. ; 336
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Tidskriftsartikel (refereegranskat)abstract
- Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4+ Treg cells. However, little is known about the CD8+ Treg cells. Therefore, we aim to characterize the CD8+ Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre-and post-bariatric surgery. A group of age-and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8+ Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8+ Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1-and Tc1/17-like CD8+ Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8+ Tregs infiltrated, compared to PB or VAT, while CD8+ Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3+CD8+ Tregs in circulation, and PD-1+CD8+ Tregs infiltrated in the VAT. An in-crease in the percentage of circulating Tc1-like CD8+ Treg cells expressing PD-1 was observed post-surgery. In conclusion, obesity induces significant alterations in CD8+ Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules.
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