Obesity enhances the recruitment of mesenchymal stem cells to visceral adipose tissue

Abstract

In obesity, high levels of TNF-α in the bone marrow microenvironment induces the bone marrow-mesenchymal stem cells (BM-MSCs) towards a pro-adipogenic phenotype. Here, we investigated the effect of obesity on the migratory potential of BM-MSCs and their fate towards the adipose tissues. BM-MSCs were isolated from male C57Bl/06 mice with high-fat diet-induced obesity. The migratory potential of the BM-MSCs, their presence in the subcutaneous (SAT) and the visceral adipose tissues (VAT), and the possible mechanisms involved were investigated. Obesity did not affect MSC content in the bone marrow but increased the frequency of MSCs in blood, SAT, and VAT. In these animals, the SAT adipocytes presented a larger area, without any changes in adipokine production or the SDF-1α gene expression. In contrast, in VAT, obesity increased leptin and IL-10 levels but did not modify the size of the adipocytes. The BM-MSCs from obese animals presented increased spontaneous migratory activity. Despite the augmented expression of CXCR4, these cells exhibited decreased migratory response toward SDF-1α, compared to that of BM-MSCs from lean mice. The PI3K-AKT pathway activation seems to mediate the migration of BM-MSCs from lean mice, but not from obese mice. Additionally, we observed an increase in the spontaneous migration of BM-MSCs from lean mice when they were co-cultured with BM-HCs from obese animals, suggesting a paracrine effect. We concluded that obesity increased the migratory potential of the BM-MSCs and induced their accumulation in VAT, which may represent an adaptive mechanism in response to chronic nutrient overload.

Important role of the SDF-1/CXCR4 axis in the homing of systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) to ovaries in rats with chemotherapy-induced premature ovarian insufficiency (POI)

“…In our studies, hAD-MSCs were used at the third passage in the experiments, and the hAD-MSC population from different clones was proven to stably express the CXCR4 protein. The results confirm the abundant CXCR4 expression in hAD-MSCs, similar to CXCR4 expression in other types of MSCs [24,35,62].…”

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

“…A Brazilian group demonstrated that [ 174 ] inflammatory cytokines—TNF alpha in particular—are able to induce the expression of CXCR4 on MSCs, which gives a plausible explanation of their enhanced migration in animal models of obesity. Moreover, leptin and interleukin-10 (IL-10) were found to be increased in visceral but not in subcutaneous WAT from obese mice, confirming site-dependent variations in the MSC microenvironment [ 21 ]. A high-fat diet is also demonstrated to promote adipogenesis and inhibit osteogenesis through leptin receptor signaling in bone marrow MSCs [ 175 ].…”

“…ADSC function is regulated by the tissue microenvironment: obesity, hypoxia and inflammation affect ADSC cellular plasticity and alter their immunophenotypic profile and regenerative functions [ 20 ]. In addition, obesity enhances their migratory potential and leads to their accumulation in visceral adipose tissue (VAT) [ 21 ].…”

Adipose Stem Cells in Modern-Day Ophthalmology

“…The proliferative actions of these cells were discovered as secondary effects of leptin secretion [2][3][4]. Adipose tissue is distributed normally around the body at sites such as the bone marrow (i.e., red adipose) [5], articular cartilage, and visceral and subcutaneous fat deposits [6][7][8][9][10]. Adipose tissue may also form around the hepatic tissue [11] and cardiac smooth muscle [12].…”