Dietary dicarboxylic acids provide a nonstorable alternative fat source that protects mice against obesity

Dicarboxylic fatty acids are generated in the liver and kidney in a minor pathway called fatty acid ω-oxidation. The effects of consuming dicarboxylic fatty acids as an alternative source of dietary fat have not been explored. Here, we fed dodecanedioic acid, a 12-carbon dicarboxylic (DC12), to mice...

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Vydáno v:	The Journal of clinical investigation Ročník 134; číslo 12
Hlavní autoři:	Goetzman, Eric S., Zhang, Bob B., Zhang, Yuxun, Bharathi, Sivakama S., Bons, Joanna, Rose, Jacob, Shah, Samah, Solo, Keaton J., Schmidt, Alexandra V., Richert, Adam C., Mullett, Steven J., Gelhaus, Stacy L., Rao, Krithika S., Shiva, Sruti S., Pfister, Katherine E., Silva Barbosa, Anne, Sims-Lucas, Sunder, Dobrowolski, Steven F., Schilling, Birgit
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States American Society for Clinical Investigation 15.06.2024
Témata:	Acyl-CoA Oxidase - genetics Acyl-CoA Oxidase - metabolism Adipose Tissue - metabolism Amino acids Animals Carboxylic acids Care and treatment Dextrose Dicarboxylic Acids - administration & dosage Dicarboxylic Acids - metabolism Dicarboxylic Acids - pharmacology Dietary fat Dietary Fats - administration & dosage Dietary Fats - metabolism Dietary Fats - pharmacology Fatty acids Fatty Acids - metabolism Glucose Health aspects Liver Liver - metabolism Male Metabolism Mice Mice, Inbred C57BL Obesity Obesity - metabolism Obesity - prevention & control Oxidases Oxidation-Reduction Peroxisomes - metabolism Physiological aspects Testing Type 2 diabetes United States Pennsylvania Fatty acid oxidation Obesity Mitochondria Metabolism
ISSN:	1558-8238, 0021-9738, 1558-8238
On-line přístup:	Získat plný text
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Shrnutí:	Dicarboxylic fatty acids are generated in the liver and kidney in a minor pathway called fatty acid ω-oxidation. The effects of consuming dicarboxylic fatty acids as an alternative source of dietary fat have not been explored. Here, we fed dodecanedioic acid, a 12-carbon dicarboxylic (DC12), to mice at 20% of daily caloric intake for 9 weeks. DC12 increased metabolic rate, reduced body fat, reduced liver fat, and improved glucose tolerance. We observed DC12-specific breakdown products in liver, kidney, muscle, heart, and brain, indicating that oral DC12 escaped first-pass liver metabolism and was utilized by many tissues. In tissues expressing the "a" isoform of acyl-CoA oxidase-1 (ACOX1), a key peroxisomal fatty acid oxidation enzyme, DC12 was chain shortened to the TCA cycle intermediate succinyl-CoA. In tissues with low peroxisomal fatty acid oxidation capacity, DC12 was oxidized by mitochondria. In vitro, DC12 was catabolized even by adipose tissue and was not stored intracellularly. We conclude that DC12 and other dicarboxylic acids may be useful for combatting obesity and for treating metabolic disorders.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1558-8238 0021-9738 1558-8238
DOI:	10.1172/JCI174186