Abstract
The pathophysiological mechanisms underlying the development of obesity and metabolic diseases are not well understood. To gain more insight into the genetic mediators associated with the onset and progression of diet-induced obesity and metabolic diseases, we studied the molecular changes in response to a high-fat diet (HFD) by using a mode-of-action by network identification (MNI) analysis. Oligo DNA microarray analysis was performed on visceral and subcutaneous adipose tissues and muscles of male C57BL/6N mice fed a normal diet or HFD for 2, 4, 8, and 12 weeks. Each of these data was queried against the MNI algorithm, and the lists of top 5 highly ranked genes and gene ontology (GO)-annotated pathways that were significantly overrepresented among the 100 highest ranked genes at each time point in the 3 different tissues of mice fed the HFD were considered in the present study. The 40 highest ranked genes identified by MNI analysis at each time point in the different tissues of mice with diet-induced obesity were subjected to clustering based on their temporal patterns. On the basis of the above-mentioned results, we investigated the sequential induction of distinct olfactory receptors and the stimulation of cancer-related genes during the development of obesity in both adipose tissues and muscles. The top 5 genes recognized using the MNI analysis at each time point and gene cluster identified based on their temporal patterns in the peripheral tissues of mice provided novel and often surprising insights into the potential genetic mediators for obesity progression.
Highlights
Microarray analysis has enabled the use of whole-genome expression profiling to understand the mechanisms underlying obesity and metabolic complications and to identify key genetic mediators
To gain more insight into the genetic mediators associated with the onset and progression of diet-induced obesity and metabolic diseases, we studied the molecular changes in response to the high-fat diet (HFD) by using an integrative time-resolved approach
When an olfactory receptor binds to its odorant, it activates a single species of G protein, the olfactory trimeric G protein (Golf), which in turn activates the olfactory isoform of adenylate cyclase (AC3) [12]
Summary
Microarray analysis has enabled the use of whole-genome expression profiling to understand the mechanisms underlying obesity and metabolic complications and to identify key genetic mediators. Microarray analysis has yielded some promising results, it is not a very practical method considering the fact that identification of genes directly affected by a condition is difficult from the hundreds to thousands of genes that exhibit changes in expression. To overcome this problem, Berneardo et al developed a model-based approach that accurately distinguishes a compound’s targets from the indirect responders [4].
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