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- Barazzoni, Rocco, et al.
(författare)
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Defining and diagnosing sarcopenia : Is the glass now half full?
- 2023
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 143
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Forskningsöversikt (refereegranskat)abstract
- Low muscle mass and function exert a substantial negative impact on quality of life, health and ultimately survival, but their definition, identification and combination to define sarcopenia have suffered from lack of universal consensus. Methodological issues have also contributed to incomplete agreement, as different approaches, techniques and potential surrogate measures inevitably lead to partly different conclusions. As a consequence: 1) awareness of sarcopenia and implementation of diagnostic procedures in clinical practice have been limited; 2) patient identification and evaluation of therapeutic strategies is largely incomplete. Significant progress has however recently occurred after major diagnostic algorithms have been developed, with common features and promising perspectives for growing consensus. At the same time, the need for further refinement of the sarcopenia concept has emerged, to address its increasingly recognized clinical heterogeneity. This includes potential differential underlying mechanisms and clinical features for age-and disease-driven sarcopenia, and the emerging challenge of sarcopenia in persons with obesity. Here, we will review existing algorithms to diagnose sarcopenia, and major open methodological issues to assess skeletal muscle mass and function under different clinical conditions, in order to highlight similarities and differences. Potential for consensus on sarcopenia diagnosis as well as emerging new challenges will be discussed.
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- Bauzá-Thorbrügge, Marco, et al.
(författare)
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Adiponectin stimulates Sca1+CD34−-adipocyte precursor cells associated with hyperplastic expansion and beiging of brown and white adipose tissue
- 2024
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- Background: The adipocyte hormone adiponectin improves insulin sensitivity and there is an inverse correlation between adiponectin levels and type-2 diabetes risk. Previous research shows that adiponectin remodels the adipose tissue into a more efficient metabolic sink. For instance, mice that overexpress adiponectin show increased capacity for hyperplastic adipose tissue expansion as evident from smaller and metabolically more active white adipocytes. In contrast, the brown adipose tissue (BAT) of these mice looks “whiter” possibly indicating reduced metabolic activity. Here, we aimed to further establish the effect of adiponectin on adipose tissue expansion and adipocyte mitochondrial function as well as to unravel mechanistic aspects in this area. Methods: Brown and white adipose tissues from adiponectin overexpressing (APN tg) mice and littermate wildtype controls, housed at room and cold temperature, were studied by histological, gene/protein expression and flow cytometry analyses. Metabolic and mitochondrial functions were studied by radiotracers and Seahorse-based technology. In addition, mitochondrial function was assessed in cultured adiponectin deficient adipocytes from APN knockout and heterozygote mice. Results: APN tg BAT displayed increased proliferation prenatally leading to enlarged BAT. Postnatally, APN tg BAT turned whiter than control BAT, confirming previous reports. Furthermore, elevated adiponectin augmented the sympathetic innervation/activation within adipose tissue. APN tg BAT displayed reduced metabolic activity and reduced mitochondrial oxygen consumption rate (OCR). In contrast, APN tg inguinal white adipose tissue (IWAT) displayed enhanced metabolic activity. These metabolic differences between genotypes were apparent also in cultured adipocytes differentiated from BAT and IWAT stroma vascular fraction, and the OCR was reduced in both brown and white APN heterozygote adipocytes. In both APN tg BAT and IWAT, the mesenchymal stem cell-related genes were upregulated along with an increased abundance of Lineage−Sca1+CD34− “beige-like” adipocyte precursor cells. In vitro, the adiponectin receptor agonist Adiporon increased the expression of the proliferation marker Pcna and decreased the expression of Cd34 in Sca1+ mesenchymal stem cells. Conclusions: We propose that the seemingly opposite effect of adiponectin on BAT and IWAT is mediated by a common mechanism; while reduced adiponectin levels are linked to lower adipocyte OCR, elevated adiponectin levels stimulate expansion of adipocyte precursor cells that produce adipocytes with intrinsically higher metabolic rate than classical white but lower metabolic rate than classical brown adipocytes. Moreover, adiponectin can modify the adipocytes' metabolic activity directly and by enhancing the sympathetic innervation within a fat depot.
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- Dichtl, Wolfgang, et al.
(författare)
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Linoleic acid-stimulated vascular adhesion molecule-1 expression in endothelial cells depends on nuclear factor-kappaB activation.
- 2002
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600 .- 0026-0495. ; 51:3, s. 327-333
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial activation is an important step in atherogenesis. In addition to established cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes mellitus, and homocysteinemia, high plasma levels of triglyceride-rich lipoproteins may be an important cause of endothelial activation as well. Free fatty acids hydrolyzed from core triglycerides of these particles can exert both pro- and anti-inflammatory effects on the vascular wall. omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to inhibit cytokine-induced endothelial activation. In contrast, we and others have previously shown that the omega-6 fatty acid linoleate activates transcription factor nuclear factor-kappaB (NF-kappaB) in endothelial cells. In this study, we show that linoleic acid stimulates vascular adhesion molecule-1 (VCAM-1) protein and mRNA expression in cultured human endothelial cells, as assessed by immunofluorescence and Northern blotting. Release of shedded soluble VCAM-1 from cultured human endothelial cells was also increased by the addition of linoleic acid, as determined by enzyme-linked immunosorbent assay (ELISA). By use of cultured rat aortic endothelial cells transfected with an IkappaB super-repressor (DeltaN2 cells), we provide evidence that NF-kappaB signalling is required in the linoleic acid-induced VCAM-1 expression in endothelial cells, whereas other transcription factors appear to be involved in the increased endothelial plasminogen activator inhibitor-1 (PAI-1) production in response to linoleic acid. These findings suggest that diets rich in linoleic acid may be proinflammatory and thus atherogenic by activating vascular endothelial cells.
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- Garrido, Pablo, et al.
(författare)
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Negative regulation of glucose metabolism in human myotubes by supraphysiological doses of 17 beta-estradiol or testosterone
- 2014
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 63:9, s. 1178-1187
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Exposure of skeletal muscle to high levels of testosterone or estrogen induces insulin resistance, but evidence regarding the direct role of either sex hormone on metabolism is limited. Therefore, the aim of this study was to investigate the direct effect of acute sex hormone exposure on glucose metabolism in skeletal muscle. Materials/Methods. Differentiated human skeletal myotubes were exposed to either 17 beta-estradiol or testosterone and metabolic characteristics were assessed. Glucose incorporation into glycogen, glucose oxidation, palmitate oxidation, and phosphorylation of key signaling proteins were determined. Results. Treatment of myotubes with either 17 beta-estradiol or testosterone decreased glucose incorporation into glycogen. Exposure of myotubes to 17 beta-estradiol reduced glucose oxidation under basal and insulin-stimulated conditions. However, testosterone treatment enhanced basal palmitate oxidation and prevented insulin action on glucose and palmitate oxidation. Acute stimulation of myotubes with testosterone reduced phosphorylation of S6K1 and p38 MAPK. Exposure of myotubes to either 17 beta-estradiol or testosterone augmented phosphorylation GSK3 beta(ser9) and PKC delta(Thr505), two negative regulators of glycogen synthesis. Treatment of myotubes with a PKC specific inhibitor (GFX) restored the effect of either sex hormone on glycogen synthesis. PKC delta silencing restored glucose incorporation into glycogen to baseline in response to 17 beta-estradiol, but not testosterone treatment. Conclusion. An acute exposure to supraphysiological doses of either 17 beta-estradiol or testosterone regulates glucose metabolism, possibly via PKC signaling pathways. Furthermore, testosterone treatment elicits additional alterations in serine/threonine kinase signaling, including the ribosomal protein S6K1 and p38 MAPK.
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