Obesity induced by a pair-fed high fat sucrose diet: methylation and expression pattern of genes related to energy homeostasis.
BACKGROUND
The expression of some genes controlling energy homeostasis could be regulated by epigenetic mechanisms that may play a role in body weight regulation. Thus, it is known that various nutritional factors affect DNA methylation. In order to assess whether the macronutrient composition of the diet could be related to the epigenetic regulation of gene expression and with obesity development, we investigated the effects on methylation and expression patterns of two pair-fed isocaloric diets in rats: control (rich in starch) and HFS (rich in fat and sucrose).


RESULTS
The pair-fed HFS diet induced higher weight gain and adiposity as compared to the controls as well as liver triglyceride accumulation and oxidative stress. Feeding the HFS diet impaired glucose tolerance and serum triglycerides and cholesterol. Liver glucokinase expression, a key glycolytic gene, remained unaltered, as well as the mRNA values of fatty acid synthase and NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6 (NDUFB6) in liver and visceral adipocytes, which regulate lipogenesis and mitochondrial oxidative metabolism, respectively. Liver expression of hydroxyacyl-coenzyme A dehydrogenase (HADHB), a key gene of beta-oxidation pathway, was higher in the HFS-fed animals. However, the methylation status of CpG islands in HADHB and glucokinase genes remained unchanged after feeding the HFS diet.


CONCLUSIONS
These results confirm that the distribution and type of macronutrients (starch vs. sucrose, and percent of fat) influence obesity onset and the associated metabolic complications. HFS diets produce obesity independently of total energy intake, although apparently no epigenetic (DNA methylation) changes accompanied the modifications observed in gene expression.
Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Pamplona, Spain.
Almudena
A
Lomba
Fermín I
FI
Milagro
Diego F
DF
García-Díaz
Amelia
A
Marti
Javier
J
Campión
J Alfredo
JA
Martínez
D050154:Adiposity; D000818:Animals; D019175:DNA Methylation; D004041:Dietary Fats / Q000008:administration & dosage*; D004734:Energy Metabolism / Q000235:genetics*; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000235:genetics*; D009765:Obesity / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D013395:Sucrose / Q000008:administration & dosage*; D014280:Triglycerides / Q000032:analysis; D015430:Weight Gain
D004041:Dietary Fats; D014280:Triglycerides; D013395:Sucrose