Transcriptome analysis revealed association of some P450 genes with obesity in a polygenic obese mouse model

Simončič, Matjaž (author), Režen, Tadeja (author), Juvan, Peter (author), Fievet, Catherine (author), Staels, Bart (author), Rozman, Damjana (author), Horvat, Simon (author)

Superfamily of cytochromoes P450 (CYP) have been extensively investigated in xenobiotic metabolism studies but only a handful of these genes (e.g., Cyp19al and Cpy7al) have been associated with obesity. Examining these associations in animal models is relevant since obesity and metabolic syndrome in humans have become a prevalent health problem. In previous studies we identified four loci affecting obesity in mouse lines selected for high (Fat line) or low (Lean line) body fat content. Here we developed a Congenic line carrying a chromosome 15 obesity segment from the Lean line and compared its liver transcriptome and obesity traits with the original Fat line. Congenic segment exibited therapeutic effect on several obesity-related parameters such as lowering fat depot size by up to 29% and lowering fasting glucose levels. Using the Steroltalk microrray focused on cytochromes P450 and cholesterol metabolism, we identified 9 differentially expressed genes including two Cyp genes (Cyp 26al, Cyp2a4). Given the scacity of literature reporting associations between obesity and Cyps, our results auggest that these genes might play a more pronounced role in regulating obesity than previously thought. Further functional studies are needed to explain the mechanism by which pertubations in these Cyps affect obesity in our polygenic model.

• Language: English
• Keywords: molekularna genetika, debelost, QTL, holesterol, presnova, laboratorijske miši
• Work type: Not categorized
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty
• Publisher: Slovensko kemijsko društvo
• Year: 2008
• Number of pages: Str. 101-110
• Numbering: Letn. 55, št. 1
• PID: 20.500.12556/RUL-58440
• UDC: 575
• ISSN on article: 1318-0207
• COBISS.SI-ID: 2272136
• Publication date in RUL: 10.07.2015

SIMONČIČ, Matjaž, REŽEN, Tadeja, JUVAN, Peter, FIEVET, Catherine, STAELS, Bart, ROZMAN, Damjana and HORVAT, Simon, 2008, Transcriptome analysis revealed association of some P450 genes with obesity in a polygenic obese mouse model. Acta chimica slovenica [online]. 2008. Vol. 55, no. 1, p. 101–110. [Accessed 17 May 2025]. Retrieved from: http://www.dlib.si/details/URN:NBN:SI:doc-2H5GFUZU

Record is a part of a journal

• Title: Acta chimica slovenica
• Shortened title: Acta chim. slov.
• Publisher: Slovensko kemijsko društvo, =Slovenian Chemical Society
• ISSN: 1318-0207
• COBISS.SI-ID: 14086149

Secondary language

• Language: English

Abstract

Proteini naddružine citokromov P450 (CYP) so dobro proučeni predvsem v povezavi s presnovo ksenobiotikov, le malo pa je znanega o vlogi genov te naddružine (npr. Cyp19al in Cyp7al) pri pojavu debelosti. Zaradi vse večjega števila bolezni, povezanih z debelostjo in metabolnim sindromom pri ljudeh, je preučevanje takih povezav na živalskih modelih v vzponu. V naših predhodnih genetskih študijah smo določili štiri lokuse, ki vplivjo na nalaganje maščevja v linijah miši, ki so bile selekcionirane na visok (debela linija) ali nizek odstotek telesnih maščob (suha linija). V tej študiji smo razvili kongeno linijo, ki vsebuje samo genomski segment kromosoma 15 iz suhe linije in primerjali njen transkriptom in druge fenotipske podatke z izvorno debelo linijo. Ugotovili smo, da ima kongeni odsek terapevtski učinek na večino z debelostjo poezanih lastnosti, kot so zmanjšanje količine posameznih maščobnih depojev ali zniževanje koncentracije glukoze v plazmi. Z uporabo Steroltalk mikromreže, ki je osredotočena na gene Cyp in gene v presnovi holesterola, smo uspeli določiti 9 diferencialno izraženih genov, ki vkljkučujejo tudi dva citokroma P450 (Cyp26al, Cyp2a4). Naši rezultati nakazuujejo, da imajo ti geni pomembno vlogo pri uravnavanju debelosti, kar dosedaj še ni bilo opisano. Da bi lahko razložili, kako so motnje v delovanju genov Cyp povezane z uravnavanjem debelosti v našem živalskem modelu, bodo potrebne nadaljnje funkcijske študije.