| 1. |
- Massier, Lucas, et al.
(författare)
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An integrated single cell and spatial transcriptomic map of human white adipose tissue
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell studies of human white adipose tissue (WAT) provide insights into the specialized cell types in the tissue. Here the authors combine publicly available and newly generated high-resolution and bulk transcriptomic results from multiple human datasets to provide a comprehensive cellular map of white adipose tissue. To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.
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| 2. |
- Goedecke, Julia H., et al.
(författare)
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An Exercise Intervention to Unravel the Mechanisms Underlying Insulin Resistance in a Cohort of Black South African Women : Protocol for a Randomized Controlled Trial and Baseline Characteristics of Participants
- 2018
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Ingår i: JMIR Research Protocols. - : JMIR PUBLICATIONS, INC. - 1929-0748. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D.Objective: The objective of the study was to examine the mechanisms underlying the changes in insulin sensitivity and secretion in response to a 12-week exercise intervention in obese black South African (SA) women.Methods: A total of 45 obese (body mass index, BMI: 30-40 kg/m2) black SA women were randomized into a control (n=22) or experimental (exercise; n=23) group. The exercise group completed 12 weeks of supervised combined aerobic and resistance training (40-60 min, 4 days/week), while the control group maintained their typical physical activity patterns, and both groups were requested not to change their dietary patterns. Before and following the 12-week intervention period, insulin sensitivity and secretion (frequently sampled intravenous glucose tolerance test) and its primary and secondary determinants were measured. Dietary intake, sleep quality and quantity, physical activity, and sedentary behaviors were measured every 4 weeks.Results: The final sample included 20 exercise and 15 control participants. Baseline sociodemographics, cardiorespiratory fitness, anthropometry, cardiometabolic risk factors, physical activity, and diet did not differ between the groups (P>.05).Conclusions: The study describes a research protocol for an exercise intervention to understand the mechanisms underlying insulin sensitivity and secretion in obese black SA women and aims to identify causal pathways underlying the high prevalence of insulin resistance and risk for T2D in black SA women, targeting specific areas for therapeutic intervention.
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| 3. |
- Mendham, Amy E., et al.
(författare)
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Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We assessed differences in mitochondrial function in gluteal (gSAT) and abdominal subcutaneous adipose tissue (aSAT) at baseline and in response to 12-weeks of exercise training; and examined depot-specific associations with body fat distribution and insulin sensitivity (S-I). Obese, black South African women (n = 45) were randomized into exercise (n = 23) or control (n = 22) groups. Exercise group completed 12-weeks of aerobic and resistance training (n = 20), while the control group (n = 15) continued usual behaviours. Mitochondrial function (high-resolution respirometry and fluorometry) in gSAT and aSAT, SI (frequently sampled intravenous glucose tolerance test), body composition (dual-energy X-ray absorptiometry), and ectopic fat (MRI) were assessed pre- and post-intervention. At baseline, gSAT had higher mitochondrial respiratory capacity and hydrogen peroxide (H2O2) production than aSAT (p < 0.05). Higher gSAT respiration was associated with higher gynoid fat (p < 0.05). Higher gSAT H2O2 production and lower aSAT mitochondrial respiration were independently associated with lower SI (p < 0.05). In response to training, S-I improved and gynoid fat decreased (p < 0.05), while H2O2 production reduced in both depots, and mtDNA decreased in gSAT (p < 0.05). Mitochondrial respiration increased in aSAT and correlated with a decrease in body fat and an increase in soleus and hepatic fat content (p < 0.05). This study highlights the importance of understanding the differences in mitochondrial function in multiple SAT depots when investigating the pathophysiology of insulin resistance and associated risk factors such as body fat distribution and ectopic lipid deposition. Furthermore, we highlight the benefits of exercise training in stimulating positive adaptations in mitochondrial function in gluteal and abdominal SAT depots.
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| 4. |
- Nankam, Pamela A. Nono, et al.
(författare)
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Changes in systemic and subcutaneous adipose tissue inflammation and oxidative stress in response to exercise training in obese black African women
- 2020
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Ingår i: Journal of Physiology. - : John Wiley & Sons. - 0022-3751 .- 1469-7793. ; 598:3, s. 503-515
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Tidskriftsartikel (refereegranskat)abstract
- Key pointsInflammation and oxidative stress are interrelated during obesity and contribute to the development of insulin resistance; and exercise training represents a key component in the management of these conditions.Black African women, despite high gluteal subcutaneous adipose tissue (SAT) and less visceral fat, are less insulin sensitive than their white counterparts.Exercise training improved systemic oxidative stress in obese black women, which was related to gynoid fat reduction and not insulin sensitivity.Inflammatory markers changed depot‐specifically in response to exercise training, increasing in gluteal SAT without changing in abdominal SAT.The increase of inflammatory state in gluteal SAT after exercise training is suggested to result from tissue remodelling consecutive to the reduction of gynoid fat but does not contribute to the improvement of whole‐body insulin sensitivity in obese black South African women.Inflammation and oxidative stress are interrelated during obesity and contribute to the development of insulin resistance. Exercise training represents a key component in the management of obesity. We evaluated the effects of 12 weeks’ combined resistance and aerobic exercise training on systemic and abdominal vs. gluteal subcutaneous adipose tissue (SAT) inflammatory and oxidative status in obese black South African women. Before and after the intervention, body composition (dual energy X‐ray absorptiometry), cardio‐respiratory fitness (VO2peak), serum and SAT inflammatory and oxidative stress markers were measured from 15 (control group) and 20 (exercise group) women and insulin sensitivity (SI; frequently sampled intravenous glucose tolerance test) was estimated. Following the intervention, VO2peak (9.8%), body fat composition (1–3%) and SI (9%) improved, serum thiobarbituric acid reactive substances (TBARS) decreased (6.5%), and catalase activity increased (23%) in the exercise compared to the control group (P < 0.05), without changes in circulating inflammatory markers. The mRNA content of interleukin‐10, tumour necrosis factor α, nuclear factor κB and macrophage migration inhibitory factor increased in the gluteal SAT exercise compared to the control group P < 0.05), with no changes in abdominal SAT. These changes of inflammatory profile in gluteal SAT, in addition to the reduction of circulating TBARS, correlated with the reduction of gynoid fat, but not with the improvement of SI. The changes in systemic oxidative stress markers and gluteal SAT inflammatory genes correlated with the reduction in gynoid fat but were not directly associated with the exercise‐induced improvements in SI.
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| 5. |
- Nankam, Pamela A. Nono, et al.
(författare)
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Circulating and Adipose Tissue Fatty Acid Composition in Black South African Women with Obesity : A Cross-Sectional Study
- 2020
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: During positive energy balance, excess lipid storage in subcutaneous adipose tissue (SAT) is associated with increased lipolysis. Elevated circulating fatty acid (FA) concentrations from both SAT lipolysis and dietary fat intake may result in visceral adipose tissue (VAT) accumulation, impairment of glucose metabolism, altogether increasing obesity-associated metabolic risks. We aimed to test the hypothesis that FA composition of red blood cell total phospholipids (RBC-TPL) and SAT is associated with body fat centralisation (VAT/SAT ratio) and insulin sensitivity (SI) in black South African women with obesity. Methods: Participants’ (n = 41) body fat composition and distribution, SI, and RBC-TPL, abdominal and gluteal SAT (gSAT) FA composition (gas-liquid chromatography) were measured. Results: RBC-TPL contained higher proportions of saturated fatty acids (SFAs) than SAT (p < 0.001), which were associated with lower SI (p < 0.05). Mono-unsaturated fatty acids (MUFAs) and stearoyl-CoA desaturase-1 (SCD1)-16 were lower, while poly-unsaturated fatty acids (PUFAs), and delta-5 and delta-6 desaturase indices were higher in RBC-TPL than SAT (p < 0.001). Interestingly, FA profiles differed between SAT depots with higher SFAs and lower MUFAs, SCD1-16 and SCD1-18 indices in abdominal compared to gluteal SAT (p < 0.01). In both SAT depots, higher SFAs and lower PUFAs (n-3 and n-6) correlated with lower VAT/SAT ratio; and lower PUFAs (n-3 and n-6) and higher total MUFA correlated with higher SI. Conclusion: Our findings confirm the relationships between the FA composition of RBC-TPL and SAT and metabolic risk in black women with obesity, which are dependent on both the FA class, and the tissue type/blood compartment in which they are distributed.
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