1. Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice
- Author
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Marianna Crispino, Francesca Guida, Adriano Lama, Gina Cavaliere, Giovanna Trinchese, Marina Prisco, Rosaria Meli, Diana Tronino, Serena Aceto, Paola Di Vaio, Claudio Pirozzi, Chiara De Filippo, Antonio Calignano, Roberto Berni Canani, Maria Pina Mollica, Giuseppina Mattace Raso, Mollica, MARIA PINA, MATTACE RASO, Giuseppina, Cavaliere, Gina, Trinchese, Giovanna, DE FILIPPO, Chiara, Aceto, Serena, Prisco, Marina, Pirozzi, Claudio, Di Guida, Francesca, Lama, Adriano, Crispino, Marianna, Tronino, Diana, DI VAIO, Paola, BERNI CANANI, Roberto, Calignano, Antonio, and Meli, Rosaria
- Subjects
0301 basic medicine ,Male ,Endocrinology, Diabetes and Metabolism ,Mitochondria, Liver ,Mitochondrion ,AMP-Activated Protein Kinases ,medicine.disease_cause ,Mitochondrial Dynamics ,Mice ,Glucose homeostasis ,Homeostasis ,Beta oxidation ,Fatty liver ,Fatty Acids ,Hep G2 Cells ,Blotting Western ,Mitochondria ,Butyrates ,Biochemistry ,Liver ,Body Composition ,Oxidation-Reduction ,medicine.medical_specialty ,AMP-Activated Protein Kinases, Acetyl-CoA Carboxylase, Animals, Blotting Western, Body Composition, Butyrates, Diet High-Fat, Energy Metabolism, Fatty Acids, Glucose Tolerance Test, Hep G2 Cells, Homeostasis, Lipid Metabolism, Mitochondria, Liver ,NF-E2-Related Factor 2 ,Blotting, Western ,Butyrate ,Carbohydrate metabolism ,Biology ,Diet, High-Fat ,Real-Time Polymerase Chain Reaction ,03 medical and health sciences ,Insulin resistance ,Microscopy, Electron, Transmission ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Humans ,Obesity ,Diet High-Fat ,Glucose Tolerance Test ,medicine.disease ,Lipid Metabolism ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,Glucose ,Insulin Resistance ,Energy Metabolism ,Oxidative stress ,Acetyl-CoA Carboxylase - Abstract
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.
- Published
- 2016