Dataset Information

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.

SUBMITTER: Calvo E

PROVIDER: S-EPMC8260805 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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

Calvo Enrique E Keiran Noelia N Núñez-Roa Catalina C Maymó-Masip Elsa E Ejarque Miriam M Sabadell-Basallote Joan J Del Mar Rodríguez-Peña María M Ceperuelo-Mallafré Victòria V Seco Jesús J Benaiges Ester E Michalopoulou Theodora T Jorba Rosa R Vendrell Joan J Fernández-Veledo Sonia S

Scientific reports 20210706 1

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 ag ...[more]

PMID: 34230537

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Project description:Brown adipose tissue (BAT) is a critical regulator of non-shivering thermogenesis and energy expenditure, offering significant potential for addressing obesity and associated metabolic disorders. Isoliquiritigenin (ISL), a natural flavonoid, has shown promising therapeutic effects in lipid metabolism-related diseases. This study aimed to explore the effects of ISL on lipid metabolism and obesity using a high-fat-diet (HFD)-induced obesity model in mice. Mice were subjected to an HFD and treated with ISL via gavage. The results demonstrated that ISL treatment significantly reduced HFD-induced weight gain and upregulated the expression of key thermogenic genes, suggesting enhanced BAT activity and thermogenesis. In vitro experiments using C3H10-T1/2 cells further supported these findings, as ISL treatment markedly increased the expression of UCP1 and PPARGC1a, which are critical regulators of thermogenesis. To elucidate the molecular mechanisms underlying ISL's effects, we conducted a transcriptomic analysis of BAT from ISL-treated mice. Pathway enrichment analysis revealed that differentially expressed genes were predominantly associated with metabolic processes, including the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and fatty acid degradation. These pathways are integral to energy metabolism and thermogenesis, providing mechanistic insights into ISL's anti-obesity effects. Additionally, ISL treatment significantly downregulated the expression of NNAT and SGK1, genes implicated in lipid metabolism and energy homeostasis. These findings suggest that ISL modulates BAT function by regulating the expression of these genes, thereby influencing lipid deposition and thermogenic capacity. In summary, this study suggests that ISL treatment has the potential to mitigate HFD-induced obesity by promoting BAT thermogenesis and modulating lipid metabolism. The molecular mechanisms involve the regulation of key metabolic pathways and genes, such as NNAT and SGK1, highlighting ISL's potential as a therapeutic agent for obesity and related metabolic disorders.

Project description:Background/aimsBrown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity.Methods and resultsHigh-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21 °C or 28 °C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21 °C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28 °C. Additionally, BMP7 resulted in extensive 'browning' of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia.ConclusionTogether, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to combat obesity and associated disorders.

Dataset Information

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

Publications

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

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