The controversial role of IL-6 in adipose tissue on obesity-induced dysregulation of glucose metabolism

Wueest, Stephan; Konrad, Daniel

doi:10.1152/ajpendo.00306.2020

Cited by 64 publications

(49 citation statements)

References 58 publications

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“…IL-6 plays a pivotal role in the regulation of both adipose tissue and skeletal muscle metabolic processes, also contributing to the cross-talk between these tissues. In particular, IL-6 released from skeletal muscle communicates with adipose tissue to induce lipolysis during fasting or exercise [51]. Moreover, IL-6 derived from skeletal muscle has been shown to suppress macrophage infiltration in adipose tissue [52].…”

Section: Figurementioning

confidence: 99%

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Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models

Feraco

Gorini

Armani

et al. 2021

IJMS

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Skeletal muscle is essential to maintain vital functions such as movement, breathing, and thermogenesis, and it is now recognized as an endocrine organ. Muscles release factors named myokines, which can regulate several physiological processes. Moreover, skeletal muscle is particularly important in maintaining body homeostasis, since it is responsible for more than 75% of all insulin-mediated glucose disposal. Alterations of skeletal muscle differentiation and function, with subsequent dysfunctional expression and secretion of myokines, play a key role in the pathogenesis of obesity, type 2 diabetes, and other metabolic diseases, finally leading to cardiometabolic complications. Hence, a deeper understanding of the molecular mechanisms regulating skeletal muscle function related to energy metabolism is critical for novel strategies to treat and prevent insulin resistance and its cardiometabolic complications. This review will be focused on both cellular and animal models currently available for exploring skeletal muscle metabolism and endocrine function.

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Section: Figurementioning

confidence: 99%

“…Moreover, IL-6 derived from skeletal muscle has been shown to suppress macrophage infiltration in adipose tissue [52]. On the other hand, in adipose tissue, IL-6 signaling pathway activation promotes macrophage infiltration, leading to a chronic state of low-grade inflammation, as well as to obesity-related insulin resistance [51,52].…”

Section: Figurementioning

confidence: 99%

Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models

Feraco

Gorini

Armani

et al. 2021

IJMS

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“…Overall, the measured cytokine concentrations fall in the same range as determined for other in vitro studies. WAT is a main source of circulating IL-6, with an about 35% contribution to basal circulating IL-6 (Wueest and Konrad, 2020). Besides adipocytes, adiposederived mesenchymal stem cells were previously found to produce loads of IL-6, too (Blaber et al, 2012); hence, the elevated IL-6 release for the ASE and AS on-chip conditions is not surprising.…”

Section: Autologous Full Complexity Wat-on-chip: Fit-for-purpose Mix-and-match Toolboxmentioning

confidence: 99%

Autologous human immunocompetent white adipose tissue-on-chip

Rogal

Roosz

et al. 2021

Preprint

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Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In the era of 'diabesity' and due to its central role for metabolic and endocrine processes, adipose tissue (specifically white adipose tissue; WAT) has become a target of high interest for therapeutic strategies. To gain insights in cellular and molecular mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models since in vitro studies on human WAT are challenging due to the large size, buoyancy, and fragility of mature white adipocytes. Leveraging the Organ-on-Chip technology, we introduce a next-generation microphysiological in vitro model of human WAT based on a tailored microfluidic platform featuring vasculature-like perfusion. The platform integrates a 3D tissue comprising all major WAT-associated cellular components in an autologous manner, including not only mature adipocytes but also organotypic endothelial barriers and stromovascular cells featuring tissue-resident innate immune cells, specifically adipose tissue macrophages. This microphysiological tissue model recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. The combination of all individual cell types with extra cellular matrix-like hydrogels in a precisely controllable bottom-up approach enables the generation of a multitude of replicates from the same donors circumventing issues of inter-donor variability and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity to fit a specific purpose via a flexible mix-and-match approach with different cell component modules. This novel WAT-on-chip system constitutes a human- based, autologous and immunocompetent in vitro model of adipose tissue that recapitulates almost full tissue heterogeneity. In the future, the new WAT-on-chip model can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.

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“…Importantly, although some BAT deposits have been reported [161,[177][178][179][180], the WAT is the predominant fat type in humans. IL-6 production by WAT has been suggested to participate in the pathophysiology of type 2 diabetes and obesity in humans [66,181,182]. Moreover, the white adipose tissue is also innervated by the sympathetic nervous system [180,183,184] and has been shown to secrete IL-6 [66].…”

Section: Translating Mouse Research Into Humansmentioning

confidence: 99%