@misc{10481/104170,
year = {2024},
month = {6},
url = {https://hdl.handle.net/10481/104170},
abstract = {Obesity represents a significant health challenge, intricately linked to conditions such as type II diabetes, metabolic syndrome, and hepatic steatosis. Several existing obesity treatments exhibit limited efficacy, undesirable side effects or a limited capability to maintain therapeutics effects in the long-term. Recently, modulation Coenzyme Q (CoQ) metabolism has emerged as a promising target for treatment of metabolic syndrome. This potential intervention could involve the modulation of endogenous CoQ biosynthesis by the use of analogs of the precursor of its biosynthesis, such as β-resorcylic acid (β-RA). Here, we show that oral supplementation with β-RA, incorporated into the diet of diet-induced obese (DIO) mice, leads to substantial weight loss. The anti-obesity effects of β-RA are partially elucidated through the normalization of mitochondrial CoQ metabolism in white adipose tissue (WAT). Additionally, we identify an HFN4α/LXR-dependent transcriptomic activation of the hepatic lipid metabolism that contributes to the anti-obesity effects of β-RA. Consequently, β-RA mitigates WAT hypertrophy, prevents hepatic steatosis, counteracts metabolic abnormalities in WAT and liver, and enhances glucose homeostasis by reducing the insulin/glucagon ratio and plasma levels of gastric inhibitory peptide (GIP). Moreover, pharmacokinetic evaluation of β-RA supports its translational potential. Thus, β-RA emerges as an efficient, safe, and translatable therapeutic option for the treatment and/or prevention of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD).},
organization = {MCIN/AEI/10.13039/501100011033; ERDF (RTI2018-093503-B-100 and PID2021-126788OB-I00)},
organization = {Junta de Andalucía (P20_00134 and PEER-0083-2020)},
organization = {Ministerio de Universidades, Spain ‘FPU program’},
organization = {University of Granada},
organization = {Consejería de Salud, Junta de Andalucía, Spain},
organization = {University of Granada (UCE-PP2017-05)},
publisher = {Elsevier},
title = {Oral β-RA induces metabolic rewiring leading to the rescue of diet-induced obesity},
doi = {10.1016/j.bbadis.2024.167283},
author = {Díaz Casado, María Elena and González García, Pilar and López Herrador, Sergio and Hidalgo Gutiérrez, Agustín and Jiménez Sánchez, Laura and Barriocanal Casado, Eliana and Bakkali, Mohamed and Van de Lest, Cha and Corral-Sarasa, Julia and Zaal, Esther A. and Berkers, Celia and López García, Luis Carlos},
}