The effect of dietary fat intake on hepatic gene expression in LG/J AND SM/J mice.
BACKGROUND
The liver plays a major role in regulating metabolic homeostasis and is vital for nutrient metabolism. Identifying the genetic factors regulating these processes could lead to a greater understanding of how liver function responds to a high-fat diet and how that response may influence susceptibilities to obesity and metabolic syndrome. In this study we examine differences in hepatic gene expression between the LG/J and SM/J inbred mouse strains and how gene expression in these strains is affected by high-fat diet. LG/J and SM/J are known to differ in their responses to a high-fat diet for a variety of obesity- and diabetes-related traits, with the SM/J strain exhibiting a stronger phenotypic response to diet.


RESULTS
Dietary intake had a significant effect on gene expression in both inbred lines. Genes up-regulated by a high-fat diet were involved in biological processes such as lipid and carbohydrate metabolism; protein and amino acid metabolic processes were down regulated on a high-fat diet. A total of 259 unique transcripts exhibited a significant diet-by-strain interaction. These genes tended to be associated with immune function. In addition, genes involved in biochemical processes related to non-alcoholic fatty liver disease (NAFLD) manifested different responses to diet between the two strains. For most of these genes, SM/J had a stronger response to the high-fat diet than LG/J.


CONCLUSIONS
These data show that dietary fat impacts gene expression levels in SM/J relative to LG/J, with SM/J exhibiting a stronger response. This supports previous data showing that SM/J has a stronger phenotypic response to high-fat diet. Based upon these findings, we suggest that SM/J and its cross with the LG/J strain provide a good model for examining non-alcoholic fatty liver disease and its role in metabolic syndrome.
Department of Anatomy and Neurobiology, Washington University in St, Louis, St, Louis, MO, USA. cpartri4@uwo.ca.
Charlyn G
CG
Partridge
Gloria L
GL
Fawcett
Bing
B
Wang
Clay F
CF
Semenkovich
James M
JM
Cheverud
D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000473:pathology; D040641:Quantitative Trait Loci; D015854:Up-Regulation / Q000235:genetics