https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/75 2026-04-04T12:28:30Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78434 Title: Namesake of PF-05231023: how nomenclature confusion leads to experimental misinterpretation in pharmacologic research Authors: Kim, Dong-Hoon; Jeong, Yong Taek 2026-01-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79256 Title: A Comprehensive Review on Medium- and Long-Chain Fatty Acid-Derived Metabolites: From Energy Sources to Metabolic Signals Authors: Park, Jin-Byung; Cho, Sungyun; Lee, Sung-Joon Abstract: Medium- and long-chain fatty acids (MLFAs) are increasingly recognized not only as metabolic substrates but also as precursors of diverse bioactive metabolites generated through host and microbial transformations. Recent advances in analytical chemistry and microbiome research have revealed that gut microorganisms catalyze extensive modifications of dietary MLFAs-producing hydroxylated, conjugated, and keto-fatty acids with enhanced potency toward host receptors. These metabolites exhibit dual activity on classical metabolic receptors, including FFAR1/4 and PPAR alpha/gamma, as well as ectopically expressed chemosensory receptors such as olfactory receptors (ORs) and bitter taste receptors (TAS2Rs). This expanded receptor landscape establishes a previously unrecognized chemosensory-metabolic axis that integrates dietary signals, microbial metabolism, and host physiology. Microbial MLFA derivatives such as 10-hydroxyoctadecenoic acid and conjugated linoleic acid regulate incretin secretion, adipogenesis, macrophage polarization, and intestinal barrier function through coordinated activation of FFARs and PPARs. Concurrently, dicarboxylic acids such as azelaic acid activate Olfr544 to modulate lipolysis, ketogenesis, GLP-1 release, and feeding behavior. TAS2Rs also sense oxidized lipids, linking lipid metabolism to immune regulation and enteroendocrine signaling. Collectively, these pathways highlight the microbiome as a metabolic transducer that converts dietary lipids into signaling molecules influencing endocrine, immune, and gut-brain circuits. Understanding the mechanisms governing MLFA bioconversion and receptor engagement provides new opportunities for therapeutic and nutritional intervention. Targeting ORs and TAS2Rs, engineering probiotics to enhance beneficial FA-derived metabolites, and developing receptor-selective synthetic analogs represent promising strategies. Future progress will require integrative approaches combining physiology, biochemistry, metabolomics, and microbial genomics to elucidate receptor specificity and host variability. 2026-01-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78931 Title: FAP PET identifies early cardiac molecular changes induced by doxorubicin chemotherapy Authors: Lee, Chul-Hee; Manzo, Onorina L.; Rubinelli, Luisa; Carrasco, Sebastian E.; Cho, Sungyun; Jeitner, Thomas M.; Babich, John; Di Lorenzo, Annarita; Kelly, James M. Abstract: Anthracycline chemotherapy, widely used in cancer treatment, poses a significant risk of cardiotoxicity that results in functional decline. Current diagnostic methods poorly predict cardiotoxicity because they do not detect early damage that precedes dysfunction. Positron emission tomography (PET) is well suited to address this need when coupled with suitable imaging biomarkers. We used PET to evaluate cardiac molecular changes in male C57BL/6J mice exposed to doxorubicin (DOX). These mice initially developed cardiac atrophy, experienced functional deficits within 10 weeks of treatment, and developed cardiac fibrosis by 16 weeks. Elevated cardiac uptake of [68Ga]Ga-FAPI-04, a PET tracer targeting fibroblast activation protein alpha (FAP), was evident by 2 weeks and preceded the onset of functional deficits. Cardiac PET signal correlated with FAP expression and activity as well as other canonical indicators of cardiac remodeling. By contrast, cardiac uptake of [18F]DPA-714 and [18F]MFBG, which target translocator protein 18 kDa and the norepinephrine transporter, respectively, did not differ between the DOX animals and their controls. These findings identify FAP as an early imaging biomarker for DOX-induced cardiac remodeling in males and support the use of FAP PET imaging to detect some cancer patients at risk for treatment-related myocardial damage before cardiac function declines. 2025-12-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78923 Title: Sodium-glucose cotransporter 2 inhibitor ameliorates thiazolidinedione-induced fluid retention through vascular leakage reduction in white adipose tissue Authors: Kim, Ji Yoon; Jang, Hye-min; Lee, Hye-Jin; Lee, Ah Hyeon; Kim, Dong-Hoon; Kim, Sin Gon; Kim, Nam Hoon Abstract: Aim Thiazolidinediones (TZDs) are effective insulin sensitisers; however, their use is restricted owing to adverse effects such as fluid retention. Previous research has linked increased vascular permeability in white adipose tissue (WAT) to TZD-induced fluid retention. We explore the potential of sodium-glucose cotransporter 2 inhibitors (SGLT2is) to counteract this side effect and elucidate the underlying mechanisms. Materials and Methods High-fat-diet-induced obese mice (C57BL/6) were assigned to three groups: (1) lobeglitazone 0.5 mg/kg (TZD monotherapy); (2) a combination of lobeglitazone 0.5 mg/kg plus empagliflozin 10 mg/kg with 0.16 mg/mL in drinking water (TZD + SGLT2i combination therapy); and (3) distilled water (control). After 6 weeks of treatment, body composition and water content in multiple tissues were measured. The expression of proteins and mRNA related to vascular permeability, renal sodium and water channels was investigated. Additionally, in vivo and in vitro experiments (the latter in human umbilical vein endothelial cells) using anti-VEGF agents were conducted. Results TZD treatment escalated vascular leakage and fluid retention in WAT, which was associated with diminished VE-cadherin expression and compromised vascular integrity. Co-treatment with the SGLT2i mitigated these adverse effects, reinstating VE-cadherin expression, reducing vascular permeability and normalizing tissue water content. Empagliflozin was found to inhibit the VEGF-A/VEGFR2 signalling pathway, thereby reducing VE-cadherin internalisation and degradation. In vitro studies reinforced these findings, emphasizing the interplay between VEGF and VE-cadherin in maintaining endothelial junction stability. Conclusions Our results suggest that SGLT2is protect against TZD-induced fluid retention by preserving vascular integrity in WAT, providing a viable therapeutic strategy to minimise TZD-associated side effects. 2025-12-01T00:00:00Z