Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome.
Both environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Over 18 weeks, the 129 strain developed features of the metabolic syndrome, notably obesity, hyperinsulinemia, and glucose intolerance only on the high-fat diet; the B6 strain on the other hand developed these features on both diets. High-fat feeding of both strains led to decreased serum triglycerides, hepatic steatosis, and hypercholesterolemia; however, B6 mice developed worse steatosis and a larger increase in LDL cholesterol. Both B6 background and high-fat feeding increased sterol regulatory element-binding protein-1c (SREBP-1c), a key regulator of lipogenic gene transcription, and its downstream targets. Stearoyl-CoA desaturase 1 (SCD1), an enzyme that regulates monounsaturated fatty acid (MUFA) synthesis, was also increased at the mRNA and enzyme activity levels by both high-fat feeding and B6 background. Furthermore, lipid analysis revealed increased hepatic triglycerides and MUFAs in B6 and high-fat-fed mice. Thus, dietary fat and genetic background act through SREBP-1c and SCD1 to affect hepatic lipid metabolism contributing to the development of the metabolic syndrome.
Biddinger
Sudha B
SB
Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Almind
Katrine
K
Miyazaki
Makoto
M
Kokkotou
Efi
E
Ntambi
James M
JM
Kahn
C Ronald
CR
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000235:genetics; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics*
D001786:Blood Glucose; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase