{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies have shown that 17β‐hydroxysteroid dehydrogenase‐13 (17β‐HSD13) is a liver‐specific, lipid droplet–associated protein that plays a crucial role in hepatic lipid metabolism. In human subjects with nonalcoholic fatty liver disease (NAFLD), its expression is markedly increased and the protein is localized to the surface of lipid droplets—findings that implicate 17β‐HSD13 in the pathogenesis of NAFLD. Its N‐terminal sequence functions as an endoplasmic reticulum and lipid droplet–targeting signal, distinguishing it from closely related enzyme family members and underscoring its liver-restricted functional specialization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAnimal model studies complement these human findings. Hepatic overexpression of human 17β‐HSD13 in mice induces a fatty liver phenotype accompanied by increased levels of key lipogenic proteins such as mature sterol regulatory element–binding protein 1 and fatty acid synthase. In contrast, genetic disruption or mutation of HSD17B13 (including a targeted S33A mutation that abolishes a conserved PKA phosphorylation site) in mice results in reduced lipolysis due to impaired interaction with adipose triglyceride lipase (ATGL) and its coactivator CGI‑58. These models further demonstrate that loss of proper 17β‐HSD13 function leads to hepatic triglyceride accumulation, increased lipid synthesis, compromised mitochondrial β‑oxidation, and inflammation, thereby advancing NAFLD and nonalcoholic steatohepatitis (NASH)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its hepatic functions, recent evidence reveals that 17β‐HSD13 is also constitutively expressed in the kidney, ureter, and urinary bladder. This wider distribution suggests that its role in lipid metabolism may extend to the renal system, possibly influencing renal lipid accumulation and contributing to the risk of chronic kidney disease in the context of NAFLD."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wen Su, Yang Wang, Xiao Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparative proteomic study reveals 17β-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1410741111"}], "href": "https://doi.org/10.1073/pnas.1410741111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25028495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25028495"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuka Horiguchi, Makoto Araki, Kiyoto Motojima "}, {"type": "b", "children": [{"type": "t", "text": "17beta-Hydroxysteroid dehydrogenase type 13 is a liver-specific lipid droplet-associated protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.03.063"}], "href": "https://doi.org/10.1016/j.bbrc.2008.03.063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18359291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18359291"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Marion Adam, Hanna Heikelä, Cyril Sobolewski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201700914R"}], "href": "https://doi.org/10.1096/fj.201700914R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29401633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29401633"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wen Su, Sijin Wu, Yongliang Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of 17β-hydroxysteroid dehydrogenase 13 at serine 33 attenuates nonalcoholic fatty liver disease in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-022-34299-1"}], "href": "https://doi.org/10.1038/s41467-022-34299-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36323699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36323699"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haibo Zhang, Jiazhen Chang, Zhihong Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and localization of HSD17B13 along mouse urinary tract."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00069.2024"}], "href": "https://doi.org/10.1152/ajprenal.00069.2024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38779753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38779753"}]}]}]}