Abstract
BackgroundAccumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. However, therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches.MethodsWe demonstrate that the effect of a combined application of photoactivation and adipose-derived stem cells (ASCs) using transplantation into visceral epididymal adipose tissue (EAT) in obesity. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND).ResultsIn diet-induced obesity, implantation of light-treated ASCs improved glucose tolerance and ameliorated systemic insulin resistance. Intriguingly, compared with non-light-treated ASCs, light-treated ASCs reduced monocyte infiltration and the levels of ATMs in EAT. Moreover, implantation of light-treated ASCs exerts more anti-inflammatory effects by suppressing M1 polarization and enhancing macrophage M2 polarization in EAT. Mass spectrometry revealed that light-treated human obese ASCs conditioned medium retained a more complete secretome with significant downregulation of pro-inflammatory cytokines and chemokines.ConclusionsThese data suggest that the combined application of photoactivation and ASCs using transplantation into dysfunctional adipose tissue contribute to selective suppression of inflammatory responses and protection from insulin resistance in obesity and type 2 diabetes.
Highlights
IntroductionDuring the progression of high-fat diet (HFD)-induced obesity, chronic low grade inflammation of visceral adipose tissue is closely linked to insulin resistance [1,2,3,4]
During the progression of high-fat diet (HFD)-induced obesity, chronic low grade inflammation of visceral adipose tissue is closely linked to insulin resistance [1,2,3,4].Enhanced adipose tissue macrophages (ATMs) appear to be a major contributing factor to the chronic inflammation associated with obesity and metabolic syndrome
Transplantation of photoactivated adipose-derived stem cells (ASCs) improves glucose homeostasis To investigate whether transplantation of photoactivatedASCs could improve glucose tolerance and insulin resistance, we fed mice high-fat chow for 16 weeks, which produced obesity and hyperglycemia (Supplementary Figure S1A-C)
Summary
During the progression of high-fat diet (HFD)-induced obesity, chronic low grade inflammation of visceral adipose tissue is closely linked to insulin resistance [1,2,3,4]. Enhanced adipose tissue macrophages (ATMs) appear to be a major contributing factor to the chronic inflammation associated with obesity and metabolic syndrome. Transplantation of subcutaneous adipose tissue into visceral depots improved systemic glucose intolerances by reducing circulating inflammatory cytokine levels in recipient HFD mice [5, 6]. Inflammatory responses in adipose tissues increase free fatty acids, facilitating insulin resistance [7]. The therapeutic applications of mesenchymal stem cells (MSCs) have been investigated in experimental and preclinical studies. Accumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. Therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches
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