Abstract
It is known that advanced metabolic disorders such as type 2 diabetes compromise the functional and regenerative capacity of endogenous adipose-tissue resident stem cells (ADSCs). It is, however, still unclear at which stage of disease progression ADSCs become compromised and whether systemic factors contribute to their functional decline. It was therefore hypothesized that inflammatory changes in the systemic microenvironment during distinct stages of disease progression negatively affect the functional capacity of ADSCs. A total of forty-seven (n = 47) black African reproductive aged females (32 ± 8 years; mean ± SD) were included in this study and subdivided into: (a) healthy lean (C; body mass index, BMI ≤ 25 kg/m2), (b) healthy overweight/obese (OB; BMI ≥ 25 kg/m2), (c) obese metabolic syndrome (MetS; BMI ≥ 30 kg/m2), and (d) type 2 diabetes mellitus (T2DM; previously diagnosed and on treatment) groups. Participants underwent anthropometric assessments and a DXA scan to determine their body composition and adipose indices. Each persons’ systemic metabolic- (cholesterol, HDL, LDL, triglycerides, and blood glucose) and inflammatory profiles (CRP, SDF1α, TNFα, IL6, IL8, IL10, and IFNy) were also evaluated. Participant-derived serum was then used to treat an ADSC cell line in vitro and its effect on viability (MTT-based assay), proliferation (BrdU), migration (wound healing assay), and osteogenic differentiation assessed. When exposed to serum derived from overweight/obese individuals (with or without metabolic syndrome), both the proliferative and migratory responses of ADSCs were less pronounced than when exposed to healthy control serum. Serum IL6 concentrations were identified as a factor influencing the proliferation of ADSCs, suggesting that long-term disruption to the systemic cytokine balance can potentially disrupt the proliferative responses of ADSCs. Obese participant-derived serum (with and without metabolic syndrome) furthermore resulted in lipid accumulation during osteogenic differentiation. This study, therefore demonstrated that systemic factors in obese individuals, regardless of the presence of metabolic syndrome, can be detrimental to the multifunctional properties of ADSCs.
Highlights
The dynamic shift to urbanization has had various implications on the lives of people globally, with an astounding increase in the prevalence of obesity (James et al, 2004; Kelly et al, 2008)
The metabolic syndrome (MetS) participants suffered from hypertension and dyslipidemia (HDL < 1.29 mmol/L and TGS levels > 1.3 mmol/L) (Figures 1E–G), suggesting that in this population with similar lifestyle and nutritional habits, disease progression occurs with age and is dependent on body composition
Even though previous studies have shown deficiencies in the functional capacity of adipose tissue-derived mesenchymal stem cell line (ADSCs)-derived from type 2 diabetic and metabolic syndrome patients (Oliva-Olivera et al, 2015; Pachón-Peña et al, 2016; Barbagallo et al, 2017), it is still unclear at which stage of disease progression ADSCs become compromised and whether systemic factors contribute to their functional decline
Summary
The dynamic shift to urbanization has had various implications on the lives of people globally, with an astounding increase in the prevalence of obesity (James et al, 2004; Kelly et al, 2008). According to the WHO, in 2014 over 600 million people worldwide were considered obese (WHO, 2018) and it is predicted that by the year 2030, approximately 1 billion people will be affected by this lifestyle related disorder (Kelly et al, 2008). This is especially evident in the female ethnic populations of developing countries such as South Africa. Disruption of the normal endocrine system function during obesity affects glucose homeostasis and causes disease progression toward metabolic syndrome (visceral adiposity with dyslipidemia) and potentially the development of T2DM (Martyniak and Masternak, 2017; Pirola and Ferraz, 2017). The microenvironment within adipose tissue has been shown to modulate the proliferation, migration, and immunophenotypic profile of ADSCs (Pachón-Peña et al, 2016)
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