Diabetes & Metabolism Journal

Original Article

Basic Research
DGAT2 Plays a Crucial Role to Control ESRRAPROX1 Transcriptional Network to Maintain Hepatic Mitochondrial Sustainability: Yoseob Lee, Yeseong Hwang, Minki Kim, Hyeonuk Jeon, Seyeon Joo, Sungsoon Fang, Jae-Woo Kim; Diabetes Metab J. 2024;48(5):901-914. Published online April 22, 2024; DOI: https://doi.org/10.4093/dmj.2023.0368

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Abstract PDF Supplementary Material PubReader ePub: Background
Diacylglycerol O-acyltransferase 2 (DGAT2) synthesizes triacylglycerol (TG) from diacylglycerol; therefore, DGAT2 is considered as a therapeutic target for steatosis. However, the consequence of inhibiting DGAT2 is not fully investigated due to side effects including lethality and lipotoxicity. In this article, we observed the role of DGAT2 in hepatocarcinoma.
Methods
The role of DGAT2 is analyzed via loss-of-function assay. DGAT2 knockdown (KD) and inhibitor treatment on HepG2 cell line was analyzed. Cumulative analysis of cell metabolism with bioinformatic data were assessed, and further compared with different cohorts of liver cancer patients and non-alcoholic fatty liver disease (NAFLD) patients to elucidate how DGAT2 is regulating cancer metabolism.
Results
Mitochondrial function is suppressed in DGAT2 KD HepG2 cell along with the decreased lipid droplets. In the aspect of the cancer, DGAT2 KD upregulates cell proliferation. Analyzing transcriptome of NAFLD and hepatocellular carcinoma (HCC) patients highlights negatively correlating expression patterns of 73 lipid-associated genes including DGAT2. Cancer patients with the lower DGAT2 expression face lower survival rate. DGAT2 KD cell and patients’ transcriptome show downregulation in estrogen- related receptor alpha (ESRRA) via integrated system for motif activity response analysis (ISMARA), with increased dimerization with corepressor prospero homeobox 1 (PROX1).
Conclusion
DGAT2 sustains the stability of mitochondria in hepatoma via suppressing ESRRA-PROX1 transcriptional network and hinders HCC from shifting towards glycolytic metabolism, which lowers cell proliferation.

Review

Metabolic Risk/Epidemiology
Hepatic Fibrosis and Cancer: The Silent Threats of Metabolic Syndrome: Scott L. Friedman; Diabetes Metab J. 2024;48(2):161-169. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0240

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Metabolic dysfunction-associated steatotic (fatty) liver disease (MASLD), previously termed non-alcoholic fatty liver disease, is a worldwide epidemic that can lead to hepatic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The disease is typically a component of the metabolic syndrome that accompanies obesity, and is often overlooked because the liver manifestations are clinically silent until late-stage disease is present (i.e., cirrhosis). Moreover, Asian populations, including Koreans, have a higher fraction of patients who are lean, yet their illness has the same prognosis or worse than those who are obese. Nonetheless, ongoing injury can lead to hepatic inflammation and ballooning of hepatocytes as classic features. Over time, fibrosis develops following activation of hepatic stellate cells, the liver’s main fibrogenic cell type. The disease is usually more advanced in patients with type 2 diabetes mellitus, indicating that all diabetic patients should be screened for liver disease. Although there has been substantial progress in clarifying pathways of injury and fibrosis, there no approved therapies yet, but current research seeks to uncover the pathways driving hepatic inflammation and fibrosis, in hopes of identifying new therapeutic targets. Emerging molecular methods, especially single cell sequencing technologies, are revolutionizing our ability to clarify mechanisms underlying MASLD-associated fibrosis and HCC.

Citations

Citations to this article as recorded by

Prognostic Impact of Metabolic Syndrome and Steatotic Liver Disease in Hepatocellular Carcinoma Using Machine Learning Techniques
Sergio Gil-Rojas, Miguel Suárez, Pablo Martínez-Blanco, Ana M. Torres, Natalia Martínez-García, Pilar Blasco, Miguel Torralba, Jorge Mateo
Metabolites.2024; 14(6): 305. CrossRef
Interplay between YAP/TAZ and metabolic dysfunction-associated steatotic liver disease progression
Na Young Lee, Myeung Gi Choi, Eui Jin Lee, Ja Hyun Koo
Archives of Pharmacal Research.2024; 47(6): 558. CrossRef
New Biomarkers in Liver Fibrosis: A Pass through the Quicksand?
Marzia Tagliaferro, Mariapaola Marino, Valerio Basile, Krizia Pocino, Gian Ludovico Rapaccini, Gabriele Ciasca, Umberto Basile, Valeria Carnazzo
Journal of Personalized Medicine.2024; 14(8): 798. CrossRef
AI Digital Pathology Using qFibrosis Shows Heterogeneity of Fibrosis Regression in Patients with Chronic Hepatitis B and C with Viral Response
Feng Liu, Yameng Sun, Dean Tai, Yayun Ren, Elaine L. K. Chng, Aileen Wee, Pierre Bedossa, Rui Huang, Jian Wang, Lai Wei, Hong You, Huiying Rao
Diagnostics.2024; 14(16): 1837. CrossRef
Conditional deletion of CEACAM1 in hepatic stellate cells causes their activation
Harrison T. Muturi, Hilda E. Ghadieh, Suman Asalla, Sumona G. Lester, Getachew D. Belew, Sobia Zaidi, Raziyeh Abdolahipour, Abhishek P. Shrestha, Agnes O. Portuphy, Hannah L. Stankus, Raghd Abu Helal, Stefaan Verhulst, Sergio Duarte, Ali Zarrinpar, Leo A.
Molecular Metabolism.2024; 88: 102010. CrossRef
The impact of traditional Chinese medicine and dietary compounds on modulating gut microbiota in hepatic fibrosis: A review
Xingting Xue, Hongbing Zhou, Jiaxing Gao, Xinghua Li, Jia Wang, Wanfu Bai, Yingchun Bai, Liya Fan, Hong Chang, Songli Shi
Heliyon.2024; 10(19): e38339. CrossRef
Beneficial Effects of Tyrosol and Oleocanthal from Extra Virgin Olive Oil on Liver Health: Insights into Their Mechanisms of Action
Daniela Gabbia
Biology.2024; 13(10): 760. CrossRef

Original Article

Complications
Impact of Hyperglycemia on Complication and Mortality after Transarterial Chemoembolization for Hepatocellular Carcinoma: Sun Joon Moon, Chang Ho Ahn, Yun Bin Lee, Young Min Cho; Diabetes Metab J. 2024;48(2):302-311. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0255

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Abstract PDF Supplementary Material PubReader ePub

Background
Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE.
Methods
A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM.
Results
Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower.
Conclusion
Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications.

Citations

Citations to this article as recorded by

Serum CYFRA 21-1 and CK19-2G2 as Predictive Biomarkers of Response to Transarterial Chemoembolization in Hepatitis C–related Hepatocellular Carcinoma Among Egyptians: A Prospective Study
Mohamed Y. Taher, Ehab Hassouna, Abeer El Hadidi, Omar El-aassar, Mohamed Fathy Bakosh, Mohamed Said Shater
Journal of Clinical and Experimental Hepatology.2025; 15(1): 102405. CrossRef

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