{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies of acyl‐CoA thioesterases in energy‐metabolizing tissues reveal that proteins such as BFIT, identified in brown adipose tissue (BAT), are acutely responsive to thermal stress. In one study, a novel, temperature‐responsive gene—robustly expressed in BAT—was shown to be induced by cold exposure and suppressed upon warm acclimation. The full‐length murine gene (and its human splice variant, hBFIT2) encodes a protein bearing two acyl‐CoA thioesterase domains that is postulated to facilitate the transition of BAT toward higher metabolic activity by modulating intracellular fatty acyl-CoA levels, potentially in relationship with obesity traits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary work has demonstrated that in the liver, a related thioesterase—Them1—regulates hepatocellular fatty acid trafficking. When expressed exclusively in hepatic tissue, Them1 was found to enhance fatty acid oxidation rates while diminishing very low-density lipoprotein (VLDL) triglyceride secretion. In the context of high-fat feeding, altered Them1 expression was linked to increased hepatic steatosis and augmented gluconeogenesis mediated by PPARα activation, underscoring its role in balancing lipid handling and glucose metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther insights into Them1’s function in BAT have revealed a dynamic intracellular regulation mechanism. Under basal conditions, Them1 aggregates into biomolecular condensates localized near lipid droplets and mitochondria, where it limits fatty acid oxidation and thermogenesis. However, upon β-adrenergic stimulation, phosphorylation at the N-terminus disrupts these puncta, allowing Them1 to adopt a diffuse distribution that relieves its suppressive effect. This stimulus-coupled reorganization finely tunes thermogenesis and energy expenditure during periods of increased energy demand."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S H Adams, C Chui, S L Schilbach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BFIT, a unique acyl-CoA thioesterase induced in thermogenic brown adipose tissue: cloning, organization of the human gene and assessment of a potential link to obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/bj3600135"}], "href": "https://doi.org/10.1042/bj3600135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11696000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11696000"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Anal Desai, Michele Alves-Bezerra, Yingxia Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of fatty acid trafficking in liver by thioesterase superfamily member 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M081455"}], "href": "https://doi.org/10.1194/jlr.M081455"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29208699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29208699"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yue Li, Norihiro Imai, Hayley T Nicholls, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-23595-x"}], "href": "https://doi.org/10.1038/s41467-021-23595-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34108467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34108467"}]}]}]}