TitleIdentification of candidate anti-obesity targets
NameRizvi, Ahmed (author), Inouye, Masayori (chair), Ron, Yacov (internal member), DiCicco-Bloom, Emanuel (internal member), Rutgers University, Graduate School - New Brunswick,
SubjectCell and Developmental Biology,
DescriptionOver the past decade, obesity has become a major health issue in the western world, and is very rapidly becoming a concern for eastern countries as well. In the most basic sense, obesity results from an imbalance between energy intake and energy expenditure. However, the complex disease that is obesity arises as a result of the insufficient energy consumption, resulting in adiposity, the increase of triglyceride storage in adipocytes, body weight gain, and an increased risk of obesity co-morbidities. As the prevalence of obesity is expected to increase over the next 20 years, the identification of novel anti-obesity targets has become paramount in the search for an efficacious and compliance-friendly obesity therapy. In an effort to identify and classify potential anti-obesity targets as experimental candidates for obesity therapy, WAT (white adipose tissue) from Hmga2-/-, Lepob.Lepob double knockout mice, Hmga2+/+ mice, Hmga2-/- mice, and Lepob/Lepob mice were run on microarray to determine gene expression profiles for each genotype. Exclusion criteria were added, and a list of 138 adipocyte-specific genes remained. The genes were then characterized through bioinformatics according to 6 parameters: 1) chromosomal location in mouse genome; 2) chromosomal location in human genome; 3) subcellular localization; 4) function; 5) knockout phenotype in mice; 6) obesity-related QTLs in human genome. After characterization, each gene was evaluated in greater detail and filtered to form a list of candidates for experimental analysis to evaluate anti-obesity effectiveness. The list of 138 genes was finally narrowed to 10 genes, 6 of which were present in the top 25 most highly expressed genes in adipocyte-rich WAT. Preliminary experimental analysis reveals diminished weight gain and overall decreased body weight in mice upon peptide inhibition for one gene from the filtered list. While we have only begun evaluating one gene, thus far, the results are encouraging in that the method used to develop and filter such a list of genes is proving to be validated. Further experimental research is required in order to fully validate each potential candidate; however such an approach, to determine solid candidates, appears promising.
NoteIncludes bibliographical references
Noteby Ahmed Hussain Rizvi
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.