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Medical Microbiology Department, College of Basic Medicine, Qingdao University, Qingdao, China
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Physiology Department, College of Basic Medicine, Qingdao University, Qingdao, China
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stimulate the release of growth hormone from the pituitary ( 1 , 2 , 3 ). Then it was reported to be also involved in the regulation of feeding ( 4 ), body weight ( 5 ), and energy metabolism ( 6 ). A key role had been established for ghrelin in energy
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aspects of MΦ-induced browning have been questioned ( 29 , 30 ), but most studies collectively support a role for MΦ in the energy metabolism of adipocytes, in particular controlling adipocyte mitochondrial function ( 26 , 27 , 31 , 32 , 33 , 34
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
Department of Nursing Physiotherapy and Medicine, SPORT Research Group (CTS-1024), CERNEP Research Center, University of Almería, Almería, Spain
Biomedical Research Unit, Torrecárdenas University Hospital, Almería, Spain
CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Granada, Spain
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Department of Medicine, Huddinge, Karolinska Institutet Campus Flemingsberg, Neo Building, Huddinge, Sweden
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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that could enhance energy metabolism ( 15 ). Preclinical experiments have identified two batokines that have a prominent effect on energy balance: fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) ( 16 , 17 ). FGF21, when
Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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Objectives
Simvastatin use is associated with muscular side effects, and increased risk for type 2 diabetes (T2D). In clinical use, simvastatin is administered in inactive lipophilic lactone-form, which is then converted to active acid-form in the body. Here, we have investigated if lactone- and acid-form simvastatin differentially affect glucose metabolism and mitochondrial respiration in primary human skeletal muscle cells.
Methods
Muscle cells were exposed separately to lactone- and acid-form simvastatin for 48 h. After pre-exposure, glucose uptake and glycogen synthesis were measured using radioactive tracers; insulin signalling was detected with Western blotting; and glycolysis, mitochondrial oxygen consumption and ATP production were measured with Seahorse XFe96 analyzer.
Results
Lactone-form simvastatin increased glucose uptake and glycogen synthesis, whereas acid-form simvastatin did not affect glucose uptake and decreased glycogen synthesis. Phosphorylation of insulin signalling targets Akt substrate 160 kDa (AS160) and glycogen synthase kinase 3β (GSK3β) was upregulated with lactone-, but not with acid-form simvastatin. Exposure to both forms of simvastatin led to a decrease in glycolysis and glycolytic capacity, as well as to a decrease in mitochondrial respiration and ATP production.
Conclusions
These data suggest that lactone- and acid-forms of simvastatin exhibit differential effects on non-oxidative glucose metabolism as lactone-form increases and acid-form impairs glucose storage into glycogen, suggesting impaired insulin sensitivity in response to acid-form simvastatin. Both forms profoundly impair oxidative glucose metabolism and energy production in human skeletal muscle cells. These effects may contribute to muscular side effects and risk for T2D observed with simvastatin use.
Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
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from anterior pituitary and named for its crucial effect on lactation ( 8 , 9 ). Recent studies have demonstrated that PRL plays an important role in regulating energy metabolism ( 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ). PRL administration
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that results in increased energy wasting and body weight loss in humans is yet to be shown. Function of human BAT: relevance for energy metabolism Soon after the detection of cold-induced BAT in human adults in 2009, numerous follow-up studies
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Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
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Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
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, 9 ). Other studies indicate that EPO has effects on lipid and energy metabolism. However, the mechanisms behind these effects remain unclear ( 10 , 11 , 12 , 13 ). Treatment with rHuEpo has been reported to improve insulin sensitivity and
Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
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hypoxia ( 3 ). Because glucose is the main source of energy for tumor cells, study of the glucose metabolism in PA will improve our understanding of the biobehavioral mechanisms of PA cell energy metabolism. While glucose is the main energy source of the
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downstream regulators ( 45 , 24 ). This interference of peripheral TH function in tissues, quantitatively important in energy metabolism, is in line with the observation that HIGH:CONV sheep did not increase their heart rate in response to a thyroxine surge
