Distinct subsets of hypothalamic genes are modulated by two different thermogenesis-inducing stimuli.
Obesity results from an imbalance between food intake and energy expenditure, two vital functions that are tightly controlled by specialized neurons of the hypothalamus. The complex mechanisms that integrate these two functions are only beginning to be deciphered. The objective of this study was to determine the effect of two thermogenesis-inducing conditions, i.e., ingestion of a high-fat (HF) diet and exposure to cold environment, on the expression of 1,176 genes in the hypothalamus of Wistar rats. Hypothalamic gene expression was evaluated using a cDNA macroarray approach. mRNA and protein expressions were determined by reverse-transcription PCR (RT-PCR) and immunoblot. Cold exposure led to an increased expression of 43 genes and to a reduced expression of four genes. HF diet promoted an increased expression of 90 genes and a reduced expression of 78 genes. Only two genes (N-methyl-D-aspartate (NMDA) receptor 2B and guanosine triphosphate (GTP)-binding protein G-alpha-i1) were similarly affected by both thermogenesis-inducing conditions, undergoing an increment of expression. RT-PCR and immunoblot evaluations confirmed the modulation of NMDA receptor 2B and GTP-binding protein G-alpha-i1, only. This corresponds to 0.93% of all the responsive genes and 0.17% of the analyzed genes. These results indicate that distinct environmental thermogenic stimuli can modulate predominantly distinct profiles of genes reinforcing the complexity and multiplicity of the hypothalamic mechanisms that regulate energy conservation and expenditure.
De Souza
Cláudio T
CT
Department of Internal Medicine, State University of Campinas, São Paulo, Brazil.
Pereira-da-Silva
Márcio
M
Araujo
Eliana P
EP
Morari
Joseane
J
Alvarez-Rojas
Fernanda
F
Bordin
Silvana
S
Moreira-Filho
Djalma C
DC
Carvalheira
José B
JB
Saad
Mario J
MJ
Velloso
Licio A
LA
D000818:Animals; D003080:Cold Temperature; D004041:Dietary Fats / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology
D004041:Dietary Fats; C522851:Gnai1 protein, rat; C121001:NR2B NMDA receptor; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D019206:GTP-Binding Protein alpha Subunits, Gi-Go