RESUMO
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.
Assuntos
Gorduras na Dieta/efeitos adversos , Estearoil-CoA Dessaturase/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Feminino , Regulação da Expressão Gênica , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Especificidade da Espécie , Estearoil-CoA Dessaturase/genética , Triglicerídeos/sangueRESUMO
Databases for genes expressed in humans or cell cultures are being developed as a part of the Human Genome Project. Because genomes respond to nutritional and other environmental variables, quantitative analyses of mRNA abundance under defined nutritional and physiological states are required to understand normal metabolism and to clarify differences between normal and disease phenotypes. Reported here are comparisons of food intake, growthp5erum lipids and expression of mRNA for hepatic stearoyl CoA desaturase (Scd1) and heart lipoprotein lipase (Lpl) in female BALB/cHnn mice following food deprivation and refeeding at the end of 2 wk of feeding semipurified diets with 3, 10 or 20% corn oils. Body weights and utilization of dietary energy were similar for mice fed all three diets. There were no differences in serum lipid concentrations associated with the level of dietary fat during subsequent food deprivation and refeeding, but significant differences in serum triglycerides and total serum cholesterol were observed between food-deprived and fed mice. Heart lipoprotein lipase and hepatic Scd1 mRNA expression levels were affected significantly by concentration of corn oil and by time after eating. These and other studies examining gene regulation by dietary variables and nutrient availability are discussed in relation to development of diet-regulated gene databases for laboratory animals fed semipurified diets.
Assuntos
Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Ingestão de Alimentos/fisiologia , Lipídeos/sangue , Lipase Lipoproteica/genética , Camundongos Endogâmicos BALB C/genética , RNA Mensageiro/metabolismo , Estearoil-CoA Dessaturase/genética , Animais , Northern Blotting , Colesterol/sangue , HDL-Colesterol/sangue , Óleo de Milho/farmacologia , Feminino , Privação de Alimentos/fisiologia , Regulação da Expressão Gênica , Metabolismo dos Lipídeos , Lipase Lipoproteica/análise , Lipase Lipoproteica/metabolismo , Fígado/metabolismo , Fígado/fisiologia , Camundongos , Camundongos Endogâmicos BALB C/metabolismo , Camundongos Endogâmicos BALB C/fisiologia , Miocárdio/enzimologia , RNA Mensageiro/análise , Estearoil-CoA Dessaturase/análise , Estearoil-CoA Dessaturase/metabolismo , Triglicerídeos/sangue , Aumento de Peso/fisiologiaRESUMO
Described is a protocol for isolating genes differentially regulated by the level of an essential nutrient in the diet. One gene, designated LFM-1 (Low Fat Mammary), was identified by subtractive hybridization and plus/minus screening in a lambda-cDNA library constructed with mRNA from mammary glands of virgin, tumor-free Balb/c mice fed a low fat diet; a second gene, stearoyl CoA desaturase, known to be regulated by the level of fat intake, was also isolated. The procedure can be modified for use with other constituents. The differential expression of LFM-1 was noted in mammary glands, liver, and kidney but not other tissues of mice fed low fat compared to high fat. LFM-1 is 86% identical to the gene encoding the e subunit of bovine F1-Fo ATPase and 89% identical to an UV-light induced gene (DDIU4) from Chinese hamster fibroblasts. Differential hybridization analyses indicated that LFM-1 may belong to a gene family.
