Effects of stem cells from inducible brown adipose tissue on diet-induced obesity in mice

Abstract

Adipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

Connexin43 in mesenchymal lineage cells regulates body adiposity and energy metabolism in mice

“…The increased glucose uptake by cKO Tw2 WAT and EMSC suggest that adipose-derived precursors in adult cKO Tw2 mice might retain a higher metabolic activity trait in adult animals, and this could be leveraged for therapeutic potential. Infusion of adipose-derived stem cells from human WAT or visceral adipose tissue into obese mice improves glucose metabolism and lipid profiles and reduces body weight gain relative to control mice (44, 45), an effect mediated by secretion of adipokines, anti-inflammatory cytokines, or angiogenic factors (46). Regardless of the mechanism, if this cell-based therapy can be translated to humans, it is conceivable that genetic or pharmacologic interference with Cx43 function in adipose-derived stem cells before infusion in obese subjects may enhance their metabolic activity.…”

Connexin43 in mesenchymal lineage cells regulates body adiposity and energy metabolism in mice

“…The increased glucose uptake by cKO Tw2 WAT and EMSCs suggest that adipose-derived precursors in adult cKO Tw2 mice might retain a higher metabolic activity trait in adult animals, and this could be leveraged for therapeutic potential. Infusion of adipose-derived stem cells from human WAT or visceral adipose tissue into obese mice improves glucose metabolism and lipid profiles and reduces body weight gain relative to control mice ( 44 , 45 ), an effect mediated by secretion of adipokines, antiinflammatory cytokines, or angiogenic factors ( 46 ). Regardless of the mechanism, if this cell-based therapy can be translated to humans, then it is conceivable that genetic or pharmacologic interference with Cx43 function in adipose-derived stem cells before infusion in obese individuals may enhance their metabolic activity.…”

Management of Obesity and Obesity-Related Disorders: From Stem Cells and Epigenetics to Its Treatment

“…Overexpression of HDAC4 in adipocytes leads to the expansion of beige adipocytes and a reduction in adiposity [103]. Stem cell or brown adipose tissue transplantation, cell lysates, and exosomes have been tested in obese mouse models [104,105]. Overall, ADSCs were found to be effective in treating obesity-associated diabetes and inflammation and protective against cardiovascular disease [106,107].…”