A Specialized cDNA Microarray (Mouse Lipid Chip) Reveals Hepatic Overexpression of Serum Amyloid A in High-fat Diet-fed Mice

Introduction

Mouse models have been widely used to explore the relationship between fat-enriched diets and the pathogenesis of atherosclerosis [1]. These strategies succeed in identifying the involvement of many specific genes in the mechanisms leading to this pathology. However, establishing links between these specific genes is difficult, and high-fat diet induced metabolic disturbance remains a complex process that is only partly understood.

Recently, the emergence of microarray technologies has made it possible to study the development of multifactorial pathologies, such as cardiovascular diseases, in a more global approach. High-density microarrays, which permit to monitor thousands of genes simultaneously, have been used to identify new signaling pathways and genomic signatures of hepatic cells in different high-fat fed mouse models [2] [3]. In addition to the general variation of genes implicated in lipid metabolism, the authors showed a broad hepatic response of multiple genes to the fat diet challenge, related to inflammatory, detoxification, and defense responses. These data support the important role of the liver in the close link between high lipid consumption and inflammatory processes. A second type of microarrays, the “custom microarrays”, permits to perform focused array experiments on a smaller scale by limiting the number of genes being interrogated [4]. In contrast to the discovery based approach of large scale genomic profiling, which involve an intensive data mining and analysis, custom arrays can be used to conduct hypothesis driven investigations [4]. To identify gene-regulatory patterns of liver lipid metabolism, we developed a specialized cDNA microarray (“Mouse Lipid Chip”) consisting of 106 specific mouse cDNAs. The cDNAs were selected to represent genes involved in lipid metabolism regulation. Using the Mouse Lipid Chip, we aimed at identifying which genes involved in the liver lipid metabolism were differentially expressed in mice fed with a high-fat diet (HFD) compared to a control diet.

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