Changes in systemic and subcutaneous adipose tissue inflammation and oxidative stress in response to exercise training in obese black African women.

KEY POINTS: Inflammation 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. ABSTRACT: 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 .

An integrated single cell and spatial transcriptomic map of human 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.

Retinol-binding protein 4 in obesity and metabolic dysfunctions.

Excessive increased adipose tissue mass in obesity is associated with numerous co-morbid disorders including increased risk of type 2 diabetes, fatty liver disease, hypertension, dyslipidemia, cardiovascular diseases, dementia, airway disease and some cancers. The causal mechanisms explaining these associations are not fully understood. Adipose tissue is an active endocrine organ that secretes many adipokines, cytokines and releases metabolites. These biomolecules referred to as adipocytokines play a significant role in the regulation of whole-body energy homeostasis and metabolism by influencing and altering target tissues function. Understanding the mechanisms of adipocytokine actions represents a hot topic in obesity research. Among several secreted bioactive signalling molecules from adipose tissue and liver, retinol-binding protein 4 (RBP4) has been associated with systemic insulin resistance, dyslipidemia, type 2 diabetes and other metabolic diseases. Here, we aim to review and discuss the current knowledge on RBP4 with a focus on its role in the pathogenesis of obesity comorbid diseases.

Contribution of Adipose Tissue Oxidative Stress to Obesity-Associated Diabetes Risk and Ethnic Differences: Focus on Women of African Ancestry.

Adipose tissue (AT) storage capacity is central in the maintenance of whole-body homeostasis, especially in obesity states. However, sustained nutrients overflow may dysregulate this function resulting in adipocytes hypertrophy, AT hypoxia, inflammation and oxidative stress. Systemic inflammation may also contribute to the disruption of AT redox equilibrium. AT and systemic oxidative stress have been involved in the development of obesity-associated insulin resistance (IR) and type 2 diabetes (T2D) through several mechanisms. Interestingly, fat accumulation, body fat distribution and the degree of how adiposity translates into cardio-metabolic diseases differ between ethnicities. Populations of African ancestry have a higher prevalence of obesity and higher T2D risk than populations of European ancestry, mainly driven by higher rates among African women. Considering the reported ethnic-specific differences in AT distribution and function and higher levels of systemic oxidative stress markers, oxidative stress is a potential contributor to the higher susceptibility for metabolic diseases in African women. This review summarizes existing evidence supporting this hypothesis while acknowledging a lack of data on AT oxidative stress in relation to IR in Africans, and the potential influence of other ethnicity-related modulators (e.g., genetic-environment interplay, socioeconomic factors) for consideration in future studies with different ethnicities.

Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function.

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 (SI). 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, SI 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.

Distinct abdominal and gluteal adipose tissue transcriptome signatures are altered by exercise training in African women with obesity.

The differential associations of adipose depots with metabolic risk during obesity have been proposed to be controlled by environmental and genetic factors. We evaluated the regional differences in transcriptome signatures between abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) in obese black South African women and tested the hypothesis that 12-week exercise training alters gene expression patterns in a depot-specific manner. Twelve young women performed 12-weeks of supervised aerobic and resistance training. Pre- and post-intervention measurements included peak oxygen consumption (VO2peak), whole-body composition and unbiased gene expression analysis of SAT depots. VO2peak increased, body weight decreased, and body fat distribution improved with exercise training (p < 0.05). The expression of 15 genes, mainly associated with embryonic development, differed between SAT depots at baseline, whereas 318 genes were differentially expressed post-training (p < 0.05). Four developmental genes were differentially expressed between these depots at both time points (HOXA5, DMRT2, DMRT3 and CSN1S1). Exercise training induced changes in the expression of genes associated with immune and inflammatory responses, and lipid metabolism in gSAT, and muscle-associated processes in aSAT. This study showed differences in developmental processes regulating SAT distribution and expandability of distinct depots, and depot-specific adaptation to exercise training in black South African women with obesity.

Exercise Training Alters Red Blood Cell Fatty Acid Desaturase Indices and Adipose Tissue Fatty Acid Profile in African Women with Obesity.

OBJECTIVE: This study assessed the changes in red blood cell total phospholipid (RBC-TPL) and subcutaneous adipose tissue (SAT) fatty acid (FA) composition in response to 12 weeks of exercise training in South African women with obesity and the associations with changes in cardiometabolic risk factors. METHODS: Previously sedentary women were randomized into control (n = 15) or exercise (n = 20) groups. RBC-TPL and SAT FA profiles, SAT gene expression, systemic inflammatory markers, liver fat, and insulin sensitivity (SI ) were measured before and after the intervention. RESULTS: Compared with control, exercise training induced decreases in RBC-TPL dihomo-γ-linolenic acid content and stearoyl-CoA desaturase-1 and increased delta-5 desaturase-estimated activity (P < 0.05). In the combined group, these changes correlated with changes in circulating leptin and TNFα (P < 0.05), as well as lower liver fat (P < 0.01). Exercise training decreased saturated FA (lauric and myristic acids) and increased polyunsaturated FA (eicosadienoic and adrenic acids) (P < 0.05) in abdominal SAT, whereas γ-linolenic acid decreased (P < 0.01) in gluteal SAT. These changes in RBC-TPL and SAT FA compositions were not associated with changes in SAT gene expression and SI . CONCLUSIONS: Exercise training alters RBC-TPL desaturase activities, which correlate with lower liver fat and systemic inflammation but not with the improvement of SI .

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.

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. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR201711002789113; http://www.pactr.org/ATMWeb/ appmanager/atm/atmregistry?_nfpb=true&_pageLabel=portals_app_atmregistry_portal_page_13 (Archived by WebCite at http://www.webcitation.org/6xLEFqKr0).