Genetic locus on rat chromosome 20 regulates diet-induced adipocyte hypertrophy: a microarray gene expression study.
Obesity is a leading cause of diabetes mellitus and hypertension. Molecular signals produced by adipose tissue may contribute to the pathogenesis of these two disorders. We showed previously that a specific segment of rat chromosome 20 (RNO20) contains a gene(s) regulating the degree of obesity, glucose intolerance, and hypertension in response to a chronic high-fat diet (HFD). Here we examined microarray gene expression profiles and cellular morphology of adipose tissues and whole body energy expenditure in this model. Adult male spontaneously hypertensive rats (SHR) and a congenic strain (SHR.1N) that differs from SHR by the above-mentioned segment of RNO20 were fed for 12 wk with HFD or a normal diet. At the end of this period, whole body energy expenditure was measured with indirect calorimetry. In response to HFD, body weight, fat pad weights, adipocyte size, and serum leptin levels increased significantly more in SHR.1N than SHR. Microarray gene expression profiles [Affymetrix, 15,923 genes and expressed sequence tags (ESTs)] showed that multiple genes of molecular pathways involved in lipogenesis were downregulated to a similar level in both strains, whereas genes involved in fatty acid oxidation and energy dissipation were upregulated less in SHR.1N than SHR. This was associated with lower whole body energy expenditure in SHR.1N than SHR at the end of the 12-wk HFD. Our results suggest that a gene(s) within the RNO20 segment regulate(s) HFD-induced increases in adiposity, and that this effect may be mediated, at least in part, by the impact of that gene(s) on fat burning and energy expenditure.
Bourdon
Céline
C
Brain and Body Centre, University of Nottingham, Nottingham, United Kingdom.
Hojna
Silvie
S
Jordan
Melissa
M
Bérubé
Julie
J
Kren
Vladimír
V
Pravenec
Michal
M
Liu
Peter
P
Arab
Sara
S
Pausová
Zdenka
Z
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002874:Chromosome Mapping; D004041:Dietary Fats / Q000008:administration & dosage*; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D006984:Hypertrophy; D020738:Leptin / Q000097:blood; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011918:Rats, Inbred SHR
D004041:Dietary Fats; D020738:Leptin