Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice (original) (raw)
Pharmacology and Therapeutics| February 21 2017
1Department of Biology, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
2Department of Pharmacy, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
1Department of Biology, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
1Department of Biology, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
1Department of Biology, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
1Department of Biology, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
1Department of Biology, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
2Department of Pharmacy, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
2Department of Pharmacy, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
2Department of Pharmacy, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
1Department of Biology, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
2Department of Pharmacy, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
2Department of Pharmacy, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
3Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
4European Laboratory for Investigation of Food Induced Diseases, University of Naples Federico II, Naples, Italy
5CEINGE Advanced Biotechnology, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
2Department of Pharmacy, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
2Department of Pharmacy, University of Naples Federico II, Naples, Italy
Search for other works by this author on:
M.P.M. and G.M.R. contributed equally to this work.
Diabetes 2017;66(5):1405–1418
Citation
Maria Pina Mollica, Giuseppina Mattace Raso, Gina Cavaliere, Giovanna Trinchese, Chiara De Filippo, Serena Aceto, Marina Prisco, Claudio Pirozzi, Francesca Di Guida, Adriano Lama, Marianna Crispino, Diana Tronino, Paola Di Vaio, Roberto Berni Canani, Antonio Calignano, Rosaria Meli; Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice. _Diabetes 1 May 2017; 66 (5): 1405–1418. https://doi.org/10.2337/db16-0924
Download citation file:
Fatty liver, oxidative stress, and mitochondrial dysfunction are key pathophysiological features of insulin resistance and obesity. Butyrate, produced by fermentation in the large intestine by gut microbiota, and its synthetic derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide, FBA, have been demonstrated to be protective against insulin resistance and fatty liver. Here, hepatic mitochondria were identified as the main target of the beneficial effect of both butyrate-based compounds in reverting insulin resistance and fat accumulation in diet-induced obese mice. In particular, butyrate and FBA improved respiratory capacity and fatty acid oxidation, activated the AMPK–acetyl-CoA carboxylase pathway, and promoted inefficient metabolism, as shown by the increase in proton leak. Both treatments consistently increased utilization of substrates, especially fatty acids, leading to the reduction of intracellular lipid accumulation and oxidative stress. Finally, the shift of the mitochondrial dynamic toward fusion by butyrate and FBA resulted in the improvement not only of mitochondrial cell energy metabolism but also of glucose homeostasis. In conclusion, butyrate and its more palatable synthetic derivative, FBA, modulating mitochondrial function, efficiency, and dynamics, can be considered a new therapeutic strategy to counteract obesity and insulin resistance.
© 2017 by the American Diabetes Association.
2017
You do not currently have access to this content.
Sign in
Pay-Per-View Access
$40.00