Lipid Level and Type Alter Stearoyl CoA Desaturase mRNA Abundance Differently in Mice with Distinct Susceptibilities to Diet-Influenced Diseases ,

Abstract

Chronic diseases develop in susceptible individuals following exposure to environmental conditions including high fat diets. Inbred strains of mice differing in susceptibility to atherosclerosis, diabetes, obesity and certain cancers are models for understanding the genetic basis and molecular mechanisms whereby diet influences these polygenic and multifactorial disorders. Expression sequence tags (EST) and disease quantitative trait loci (QTL) are also being identified with these strains. Reported here are comparisons of food intake, growth, nonfasting serum lipids and expression of mRNA for hepatic apolipoprotein E (ApoE), hepatic stearoyl CoA desaturase (Scd1) and heart lipoprotein lipase (Lpl) in a 2 x 2 x 2 design with C57BL/6J and BALB/cByJ mice fed semipurified diets with 4 or 20% saturated (coconut) or unsaturated (corn) oils for 4 mo. Histological studies of aortas and coronary arteries are also reported for these animals. After 4 mo, BALB/cByJ mice were significantly heavier and had significantly higher total serum cholesterol, HDL cholesterol and triglyceride concentrations in the fed state than C57BL/6J mice. Efficiency of utilizing dietary energy did not differ consistently between strains. Oil level affected serum total cholesterol, triglycerides and HDL cholesterol, which were significantly greater in mice fed high fat diets. Lpl and ApoE mRNA expression levels were not significantly affected by mouse strain, oil source or oil level. Scd1 mRNA expression, however, was significantly higher in C57BL/6J than in BALB/cByJ mice and was lower in all mice fed 20% compared with those fed 4% fat diets. Genes regulated differently by diet among strains with distinct susceptibility to diet-influenced disease may be associated with molecular pathways contributing to incidence or severity.

Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: Transcriptomic analysis of the effects of eicosapentaenoic acid- and arachidonic acid-enriched diets

“…This was to minimize the variation in time between the last food intake and tissue sampling [25]. A maximum of 12 mice were euthanized on each day; 14 h overnight fasting and tissue sampling were staggered in three groups of four mice, with 1 h between each group.…”

Coordinated Upregulation of Oxidative Pathways and Downregulation of Lipid Biosynthesis Underlie Obesity Resistance in Perilipin Knockout Mice

“…Scd expression is modulated by dietary factors (e.g., polyunsaturated fatty acids, cholesterol, vitamin A [21][22][23]), hormonal signals (e.g., insulin, glucagon [24]), environmental factors (e.g., temperature changes, thiazolinediones, metals, alcohol, phenolic compounds [25][26][27][28]), peroxisomal proliferators (29), and developmental processes (30). Altered Scd activity has been observed in a wide range of disorders, including diabetes, atherosclerosis, cancer, obesity, and viral infections (25,31,32).…”

Nutrient selection through nutrigenomic approaches

“…Since dietary chemicals are regularly ingested and participate indirectly and directly in regulating gene expression, it follows that a subset of genes regulated by diet must be involved in disease initiation, progression, and severity (79,113). The clearest example of genotype-diet interactions in chronic disease is type 2 diabetes, a condition that frequently occurs in sedentary, obese individuals and certain minority groups (13,15).…”

“…The limitation of a unique genotype can be overcome by examining multiple strains of mice (159). One of our laboratories (79,113) introduced a comparative method for laboratory animals that identifies genes regulated differently by dietary variables between two or more genotypes. The genotypes (or inbred strains) of mice are selected based upon their susceptibility to disease caused by diet.…”

“…We found that certain genes were differentially regulated based upon genotype (in this case, A vy /A obese yellow vs. A/a agouti mice) and/or on caloric intake (100% vs. 70% calories) or by the interaction between diet and genotype (Kaput et al, unpublished observations). The criteria for identifying a candidate disease gene are 1) genes must be differentially regulated by diet and/or 2) differentially regulated by genotype and 3) must map to chromosomal regions [e.g., quantitative trait loci (QTL)] associated with the disease (79,113). This approach identifies candidate genes in an unbiased manner, and additional testing in humans or animal models is necessary to validate these.…”