| First Author | Heden TD | Year | 2023 |
| Journal | JCI Insight | Volume | 8 |
| Issue | 18 | PubMed ID | 37561578 |
| Mgi Jnum | J:340883 | Mgi Id | MGI:7531258 |
| Doi | 10.1172/jci.insight.160987 | Citation | Heden TD, et al. (2023) ACOT1 deficiency attenuates high-fat diet-induced fat mass gain by increasing energy expenditure. JCI Insight 8(18):e160987 |
| abstractText | Acyl-CoA thioesterase 1 (ACOT1) catalyzes the hydrolysis of long-chain acyl-CoAs to free fatty acids and CoA and is typically upregulated in obesity. Whether targeting ACOT1 in the setting of high-fat diet-induced (HFD-induced) obesity would be metabolically beneficial is not known. Here we report that male and female ACOT1KO mice are partially protected from HFD-induced obesity, an effect associated with increased energy expenditure without alterations in physical activity or food intake. In males, ACOT1 deficiency increased mitochondrial uncoupling protein-2 (UCP2) protein abundance while reducing 4-hydroxynonenal, a marker of oxidative stress, in white adipose tissue and liver of HFD-fed mice. Moreover, concurrent knockdown (KD) of UCP2 with ACOT1 in hepatocytes prevented increases in oxygen consumption observed with ACOT1 KD during high lipid loading, suggesting that UCP2-induced uncoupling may increase energy expenditure to attenuate weight gain. Together, these data indicate that targeting ACOT1 may be effective for obesity prevention during caloric excess by increasing energy expenditure. |
