micro
            <scp>RNA</scp>
            ‐379 couples glucocorticoid hormones to dysfunctional lipid homeostasis

Guia, Roldan M. de; Rose, Adam J.; Sommerfeld, Anke; Seibert, Oksana; Strzoda, Daniela; Zota, Annika; Feuchter, Yvonne; Krones-Herzig, Anja; Sijmonsma, Tjeerd P.; Kirilov, Milen; Sticht, Carsten; Gretz, Norbert; Dallinga‐Thie, Geesje M.; Diederichs, Sven; Klöting, Nora; Blüher, Matthias; Díaz, Mauricio Berriel; Herzig, Stephan

doi:10.15252/embj.201490464

Cited by 39 publications

(35 citation statements)

References 63 publications

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“…Liver and AT biopsy specimens were taken during surgery, immediately snap-frozen in liquid nitrogen, and stored at 280°C until further preparations. Measurement of total body and liver fat, tissue sample handling, and analysis of blood samples, including measurement of serum adiponectin and leptin concentrations, was performed as previously described (19,20). IL-6 plasma concentrations were measured by a high-sensitivity Human IL-6 Quantikine ELISA Kit (R&D Systems, Oxford, U.K.).…”

Section: Methodsmentioning

confidence: 99%

Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance

et al. 2015

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Hepatic steatosis and insulin resistance are among the most prevalent metabolic disorders and are tightly associated with obesity and type 2 diabetes. However, the underlying mechanisms linking obesity to hepatic lipid accumulation and insulin resistance are incompletely understood. Glycoprotein 130 (gp130) is the common signal transducer of all interleukin 6 (IL-6) cytokines. We provide evidence that gp130-mediated adipose tissue lipolysis promotes hepatic steatosis and insulin resistance. In obese mice, adipocyte-specific gp130 deletion reduced basal lipolysis and enhanced insulin's ability to suppress lipolysis from mesenteric but not epididymal adipocytes. Consistently, free fatty acid levels were reduced in portal but not in systemic circulation of obese knockout mice. Of note, adipocyte-specific gp130 knockout mice were protected from high-fat diet-induced hepatic steatosis as well as from insulin resistance. In humans, omental but not subcutaneous IL-6 mRNA expression correlated positively with liver lipid accumulation (r = 0.31, P < 0.05) and negatively with hyperinsulinemic-euglycemic clamp glucose infusion rate (r = 20.28, P < 0.05). The results show that IL-6 cytokineinduced lipolysis may be restricted to mesenteric white adipose tissue and that it contributes to hepatic insulin resistance and steatosis. Therefore, blocking IL-6 cytokine signaling in (mesenteric) adipocytes may be a novel approach to blunting detrimental fat-liver crosstalk in obesity.

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Section: Methodsmentioning

confidence: 99%

Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance

et al. 2015

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“…activating key enzymes such as PNPLA2 (35) as well as inducing specific microRNAs that have the potential to modulate lipid homeostasis (49).…”

Section: In Vivo Animal Modelsmentioning

confidence: 99%

Glucocorticoids and non-alcoholic fatty liver disease

Woods

Hazlehurst

Tomlinson

2015

The Journal of Steroid Biochemistry and Molecular Biology

135

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Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the global obesity and metabolic disease epidemic and is rapidly becoming the leading cause of liver cirrhosis and indication for liver transplantation worldwide. The hallmark pathological finding in NAFLD is excess lipid accumulation within hepatocytes, but it is a spectrum of disease ranging from benign hepatic steatosis to steatohepatitis through to fibrosis, cirrhosis and risk of hepatocellular carcinoma. The exact pathophysiology remains unclear with a multi-hit hypothesis generally accepted as being required for inflammation and fibrosis to develop after initial steatosis. Glucocorticoids have been implicated in the pathogenesis of NAFLD across all stages. They have a diverse array of metabolic functions that have the potential to drive NAFLD acting on both liver and adipose tissue. In the fasting state, they are able to mobilize lipid, increasing fatty acid delivery and in the fed state can promote lipid accumulation. Their action is controlled at multiple levels and in this review will outline the evidence base for the role of GCs in the pathogenesis of NAFLD from cell systems, rodent models and clinical studies and describe interventional strategies that have been employed to modulate glucocorticoid action as a potential therapeutic strategy.

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“…In mammals, although GCs are crucial for the maintenance of energy metabolism homeostasis, GC excess is associated with metabolic disturbances (Karatsoreos et al, 2010;Weigensberg, Toledo-Corral, & Goran, 2008). The undesirable effects of GC excess for metabolism are mostly explained by its actions in the liver (de Guia et al, 2015), muscle (Buren, Lai, Lundgren, Eriksson, & Jensen, 2008) and WAT (Christ-Crain et al, 2008). However, its role in BAT is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Brown adipose tissue remodelling induced by corticosterone in male Wistar rats

Mousovich-Neto

Matos

Costa

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?Does glucocorticoid excess disrupt brown adipose tissue (BAT) phenotype and function? What is the main finding and its importance?Glucocorticoid excess induced an extensive remodelling of interscapular BAT, resulting in a white‐like phenotype in association with metabolic disturbances. Glucocorticoids might be an important modulator of BAT physiology and BAT may have a role in pathophysiology of metabolic disturbances induced by glucocorticoid excess. Abstract In mammals, brown adipose tissue (BAT) is centrally involved in energy metabolism. To test the hypothesis that glucocorticoid excess disrupts BAT phenotype and function, male Wistar rats were treated with corticosterone in drinking water for 21 days. To confirm induction of glucocorticoid excess and metabolic disturbances, adrenal weight, corticotrophin releasing hormone mRNA levels and corticosterone serum levels were measured and a glucose tolerance test and serum triacylglycerol analyses were performed. Adipose tissue deposits were excised, weighed and evaluated by a set of biochemical, histological and molecular procedures, including thin‐layer chromatography, histochemistry, immunohistochemistry, quantitative real‐time polymerase chain reaction, high‐resolution oxygraphy, ATP synthesis and enzymatic activity measurements. The approach was successful in induction of glucocorticoid excess and metabolic disturbances. Lower body weight and increased adiposity were observed in corticosterone‐treated rats. Interscapular brown adipose tissue (iBAT) showed higher sensitivity to glucocorticoids than other fat deposits. The treatment induced lipid accumulation, unilocular rearrangement, increased collagen content and decreased innervation in iBAT. Furthermore, expression of Prdm16 (P < 0.05), Ucp1 (P <0.05) and Slc7a10 (P <0.05) mRNA decreased, while expression of Fasn (P <0.05) and Lep (P <0.05) mRNA increased in brown adipose tissue. Also, the levels of UCP1 diminished (P <0.001, 2.5‐fold). Finally, lower oxygen consumption (P <0.05), ATP synthesis (P <0.05) and mitochondrial content (P <0.05) were observed in iBAT of glucocorticoid‐treated rats. Glucocorticoid excess induced an extensive remodelling of interscapular brown adipose tissue, resulting in a white‐like phenotype in association with metabolic disturbances.

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micro RNA ‐379 couples glucocorticoid hormones to dysfunctional lipid homeostasis

Cited by 39 publications

References 63 publications

Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance

Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance

Glucocorticoids and non-alcoholic fatty liver disease

Brown adipose tissue remodelling induced by corticosterone in male Wistar rats

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