Grandoch 2019 Nat Metab: Difference between revisions
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== Correction: NADH and Complex I == | == Correction: NADH and Complex I == | ||
:::: '''NADH''' is shown as the '''''product''''' of the reaction catalyzed by CI in respiration. This error is rare in the literature, but comparable to the | :::: '''NADH''' is shown as the '''''product''''' of the reaction catalyzed by CI in respiration. This error is rare in the literature, but comparable to the error frequently encountered when '''FADH<sub>2</sub>''' is shown as the '''''substrate''''' of CII. For details see Ref [1]. | ||
:::# Gnaiger E (2023) Complex II ambiguities β FADH<sub>2</sub> in the electron transfer system. MitoFit Preprints 2023.3. https://doi.org/10.26124/mitofit:2023-0003.v2 | :::# Gnaiger E (2023) Complex II ambiguities β FADH<sub>2</sub> in the electron transfer system. MitoFit Preprints 2023.3. https://doi.org/10.26124/mitofit:2023-0003.v2 |
Revision as of 00:59, 10 April 2023
Grandoch M, FlΓΆgel U, Virtue S, Maier JK, Jelenik T, Kohlmorgen C, Feldmann K, Ostendorf Y, CastaΓ±eda TR, Zhou Z, Yamaguchi Y, Nascimento EBM, Sunkari VG, Goy C, Kinzig M, SΓΆrgel F, Bollyky PL, Schrauwen P, Al-Hasani H, Roden M, Keipert S, Vidal-Puig A, Jastroch M5, Haendeler J, Fischer JW (2019) 4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue. Nat Metab 1:546-59. |
Grandoch M, Floegel U, Virtue S, Maier JK, Jelenik T, Kohlmorgen C, Feldmann K, Ostendorf Y, Castaneda TR, Zhou Z, Yamaguchi Y, Nascimento EBM, Sunkari VG, Goy C, Kinzig M, Soergel F, Bollyky PL, Schrauwen P, Al-Hasani H, Roden M, Keipert S, Vidal-Puig A, Jastroch M, Haendeler J, Fischer JW (2019) Nat Metab
Abstract: Therapeutic increase of brown adipose tissue (BAT) thermogenesis is of great interest as BAT activation counteracts obesity and insulin resistance. Hyaluronan (HA) is a glycosaminoglycan, found in the extracellular matrix, which is synthesized by HA synthases (Has1/Has2/Has3) from sugar precursors and accumulates in diabetic conditions. Its synthesis can be inhibited by the small molecule 4-methylumbelliferone (4-MU). Here, we show that the inhibition of HA-synthesis by 4-MU or genetic deletion of Has2/Has3 improves BAT`s thermogenic capacity, reduces body weight gain, and improves glucose homeostasis independently from adrenergic stimulation in mice on diabetogenic diet, as shown by a magnetic resonance T2 mapping approach. Inhibition of HA synthesis increases glycolysis, BAT respiration and uncoupling protein 1 expression. In addition, we show that 4-MU increases BAT capacity without inducing chronic stimulation and propose that 4-MU, a clinically approved prescription-free drug, could be repurposed to treat obesity and diabetes.
β’ Bioblast editor: Plangger M β’ O2k-Network Lab: DE Duesseldorf Roden M, DE Duesseldorf Haendeler J, NL Maastricht Schrauwen P, DE Munich Jastroch M
Correction: NADH and Complex I
- NADH is shown as the product of the reaction catalyzed by CI in respiration. This error is rare in the literature, but comparable to the error frequently encountered when FADH2 is shown as the substrate of CII. For details see Ref [1].
- Gnaiger E (2023) Complex II ambiguities β FADH2 in the electron transfer system. MitoFit Preprints 2023.3. https://doi.org/10.26124/mitofit:2023-0003.v2
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, Pharmacology;toxicology
Pathology: Diabetes
Organism: Mouse Tissue;cell: Fat Preparation: Permeabilized tissue, Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET
Pathway: N, NS, ROX
HRR: Oxygraph-2k
Labels, 2019-10