소장자료
LDR | 03853nam 2200493 4500 | ||
001 | 0100803787▲ | ||
005 | 20240329141117▲ | ||
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008 | 240116s2021 us |||||||||||||||c||eng d▲ | ||
020 | ▼a9798379603700▲ | ||
035 | ▼a(MiAaPQ)AAI30557108▲ | ||
040 | ▼aMiAaPQ▼cMiAaPQ▲ | ||
082 | 0 | ▼a610▲ | |
100 | 1 | ▼aOrabi, Danny Ahmad.▲ | |
245 | 1 | 0 | ▼aThe Effects of High Fat Diet on Liver Disease and Hepatocellular Carcinoma▼h[electronic resource]▲ |
260 | ▼a[S.l.]: ▼bCase Western Reserve University. ▼c2021▲ | ||
260 | 1 | ▼aAnn Arbor : ▼bProQuest Dissertations & Theses, ▼c2021▲ | |
300 | ▼a1 online resource(261 p.)▲ | ||
500 | ▼aSource: Dissertations Abstracts International, Volume: 84-12, Section: B.▲ | ||
500 | ▼aAdvisor: Brown, Jonathan Mark;Lathia, Justin.▲ | ||
502 | 1 | ▼aThesis (Ph.D.)--Case Western Reserve University, 2021.▲ | |
506 | ▼aThis item must not be sold to any third party vendors.▲ | ||
520 | ▼aObjective - The rise of obesity and metabolic syndrome has seen it become a leading etiology of chronic liver disease and primary liver cancer, the latter most commonly being hepatocellular carcinoma (HCC). Mechanistic drivers of disease are being explored to generate effective therapeutic options. Herein, we sought to explore the effects of high fat diet focusing on liver disease and HCC.Approach and Results - A literature review was performed and used to guide this body of work. In a rodent model, a single high fat diet meal equivalent was found to significantly alter the gut microbial composition, hepatic transcriptome, and both the hepatic and plasma metabolomes. These latter changes were observed in a gut microbiome-dependent manner, highlighting its role in high fat diet-mediated metabolic dysfunction. A composite of "multi-omic" data and novel analytic software tools were made publicly available for further investigation. Next, a novel mouse microsurgical model to achieve physiologically relevant administration of gut microbial metabolites was developed. The portal vein infusion of a single gut microbial metabolite, 4-hydroxyphenylacetic acid (4-HPAA), significantly altered the hepatic transcriptome. Lastly, the role of the recently discovered serine hydrolase alpha/beta-hydrolase domain 6 (ABHD6) found to be relevant to high fat diet-mediated metabolic syndrome and liver disease was explored as a potential therapeutic in HCC. ABHD6 inhibition was found to alter saturated fatty acid-induced autophagy in a human hepatoma cell line and reduce HCC development and progression in two mouse model of disease.Conclusion - As rates of liver disease and HCC secondary to metabolic dysfunction rise, novel mechanistic insights and treatment options are needed. The gut microbiome plays an intimate role in high fat diet-mediated metabolic dysfunction. The inhibition of ABHD6, previously shown to be a therapeutic avenue in metabolic syndrome, also demonstrates independent antitumorigenic properties in HCC making it an attractive target for both the treatment of fatty liver disease and the chemoprevention of HCC.▲ | ||
590 | ▼aSchool code: 0042.▲ | ||
650 | 4 | ▼aMedicine.▲ | |
650 | 4 | ▼aMolecular biology.▲ | |
650 | 4 | ▼aNutrition.▲ | |
653 | ▼aObesity▲ | ||
653 | ▼aChronic liver disease▲ | ||
653 | ▼aHepatocellular carcinoma▲ | ||
653 | ▼aHigh fat diet▲ | ||
690 | ▼a0564▲ | ||
690 | ▼a0307▲ | ||
690 | ▼a0570▲ | ||
710 | 2 | 0 | ▼aCase Western Reserve University.▼bMolecular Medicine.▲ |
773 | 0 | ▼tDissertations Abstracts International▼g84-12B.▲ | |
773 | ▼tDissertation Abstract International▲ | ||
790 | ▼a0042▲ | ||
791 | ▼aPh.D.▲ | ||
792 | ▼a2021▲ | ||
793 | ▼aEnglish▲ | ||
856 | 4 | 0 | ▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16933780▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.▲ |
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The Effects of High Fat Diet on Liver Disease and Hepatocellular Carcinoma[electronic resource]
자료유형
국외eBook
서명/책임사항
The Effects of High Fat Diet on Liver Disease and Hepatocellular Carcinoma [electronic resource]
발행사항
[S.l.] : Case Western Reserve University. 2021 Ann Arbor : ProQuest Dissertations & Theses , 2021
형태사항
1 online resource(261 p.)
일반주기
Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
Advisor: Brown, Jonathan Mark;Lathia, Justin.
Advisor: Brown, Jonathan Mark;Lathia, Justin.
학위논문주기
Thesis (Ph.D.)--Case Western Reserve University, 2021.
요약주기
Objective - The rise of obesity and metabolic syndrome has seen it become a leading etiology of chronic liver disease and primary liver cancer, the latter most commonly being hepatocellular carcinoma (HCC). Mechanistic drivers of disease are being explored to generate effective therapeutic options. Herein, we sought to explore the effects of high fat diet focusing on liver disease and HCC.Approach and Results - A literature review was performed and used to guide this body of work. In a rodent model, a single high fat diet meal equivalent was found to significantly alter the gut microbial composition, hepatic transcriptome, and both the hepatic and plasma metabolomes. These latter changes were observed in a gut microbiome-dependent manner, highlighting its role in high fat diet-mediated metabolic dysfunction. A composite of "multi-omic" data and novel analytic software tools were made publicly available for further investigation. Next, a novel mouse microsurgical model to achieve physiologically relevant administration of gut microbial metabolites was developed. The portal vein infusion of a single gut microbial metabolite, 4-hydroxyphenylacetic acid (4-HPAA), significantly altered the hepatic transcriptome. Lastly, the role of the recently discovered serine hydrolase alpha/beta-hydrolase domain 6 (ABHD6) found to be relevant to high fat diet-mediated metabolic syndrome and liver disease was explored as a potential therapeutic in HCC. ABHD6 inhibition was found to alter saturated fatty acid-induced autophagy in a human hepatoma cell line and reduce HCC development and progression in two mouse model of disease.Conclusion - As rates of liver disease and HCC secondary to metabolic dysfunction rise, novel mechanistic insights and treatment options are needed. The gut microbiome plays an intimate role in high fat diet-mediated metabolic dysfunction. The inhibition of ABHD6, previously shown to be a therapeutic avenue in metabolic syndrome, also demonstrates independent antitumorigenic properties in HCC making it an attractive target for both the treatment of fatty liver disease and the chemoprevention of HCC.
주제
ISBN
9798379603700
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