The aqueous fraction of Castanea crenata inner shell extract reduces obesity and intramuscular lipid accumulation via induction of mitochondrial respiration and fatty acid oxidation in muscle

Phytomedicine. 2022 Apr:98:153974. doi: 10.1016/j.phymed.2022.153974. Epub 2022 Feb 2.

Abstract

Background: Skeletal muscle is responsible for free fatty acid (FFA) disposal via mitochondrial respiration and fatty acid oxidation (FAO). Obesity triggers high levels of circulating FFAs, which can cause intramuscular lipid (IMCL) deposition. Diverse phytochemicals, including crude Castanea crenata inner shell extract (CCE), have been shown to possess an anti-obesity effect.

Purpose: We aimed to demonstrate whether the aqueous fraction of CCE (ACCE) provides an anti-obesity effect with a decrease in plasma FFAs and reduces IMCL.

Methods: High-fat-fed C57BL/6 mice received ACCE via water intake. A204 cells incubated with fatty acids were treated with ACCE. Lipid accumulation and mitochondrial metabolism were assessed using histological and molecular techniques.

Results: ACCE possessed a notably higher gallic acid content than CCE among the constituents. ACCE-administered mice exhibited reduced plasma FFA levels, adiposity, and IMCL. Muscle lipotoxicity was suppressed, including apoptosis, ER stress, and inflammation. The anti-lipid effect of ACCE was observed with the induction of mitochondrial respiration and fatty acid oxidation in muscle.

Conclusions: ACCE increases mitochondrial respiration and FAO in skeletal muscle and protects muscle from IMCL and lipotoxicity, reducing plasma FFA and adiposity.

Keywords: Castanea crenata; Chestnut; High-fat diet; Mitochondria; Muscle.