Respiratory metabolism Scientific Publications

Latest publication 02/06/2020

Muscle_derived GDF15 drives diurnal anorexia and systemic metabolic remodeling d

Mitochondrial dysfunction promotes metabolic stress responses in a cell_autonomous as well as organismal manner. The wasting hormone growth...

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    [title] => Muscle_derived GDF15 drives diurnal anorexia and systemic metabolic remodeling d
    [paragraph] => Muscle_derived GDF15 drives diurnal anorexia and systemic metabolic remodeling during mitochondrial stress
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Authors
M Ost, CI Gil, V Coleman, S Keipert, S Efstathiou et al

 Lab
Department of Physiology of Energy Metabolism, German Institute of Human Nutrition Potsdam_Rehbrücke, Nuthetal, Germany
Journal
EMBO Reports
Abstract
Mitochondrial dysfunction promotes metabolic stress responses in a cell_autonomous as well as organismal manner. The wasting hormone growth differentiation factor 15 (GDF15) is recognized as a biomarker of mitochondrial disorders, but its pathophysiological function remains elusive. To test the hypothesis that GDF15 is fundamental to the metabolic stress response during mitochondrial dysfunction, we investigated transgenic mice (Ucp1_TG) with compromised muscle_specific mitochondrial OXPHOS capacity via respiratory uncoupling. Ucp1_TG mice show a skeletal muscle_specific induction and diurnal variation of GDF15 as a myokine. Remarkably, genetic loss of GDF15 in Ucp1_TG mice does not affect muscle wasting or transcriptional cell_autonomous stress response but promotes a progressive increase in body fat mass. Furthermore, muscle mitochondrial stress_induced systemic metabolic flexibility, insulin sensitivity, and white adipose tissue browning are fully abolished in the absence of GDF15. Mechanistically, we uncovered a GDF15_dependent daytime_restricted anorexia, whereas GDF15 is unable to suppress food intake at night. Altogether, our evidence suggests a novel diurnal action and key pathophysiological role of mitochondrial stress_induced GDF15 in the regulation of systemic energy metabolism.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)
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An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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