Identification of adipocyte genes regulated by caloric intake.
BACKGROUND
Changes in energy intake have marked and rapid effects on metabolic functions, and some of these effects may be due to changes in adipocyte gene expression that precede alterations in body weight.


OBJECTIVE
The aim of the study was to identify adipocyte genes regulated by changes in caloric intake independent of alterations in body weight.


METHODS
Obese subjects given a very low-caloric diet followed by gradual reintroduction of ordinary food and healthy subjects subjected to overfeeding were investigated. Adipose tissue biopsies were taken at multiple time-points, and gene expression was measured by DNA microarray. Genes regulated in the obese subjects undergoing caloric restriction followed by refeeding were identified using two-way ANOVA corrected with Bonferroni. From these, genes regulated by caloric restriction and oppositely during the weight-stable refeeding phase were identified in the obese subjects. The genes that were also regulated, in the same direction as the refeeding phase, in the healthy subjects after overfeeding were defined as being regulated by caloric intake. Results were confirmed using real-time PCR or immunoassay.


RESULTS
Using a significance level of P < 0.05 for all comparisons, 52 genes were down-regulated, and 50 were up-regulated by caloric restriction and regulated in the opposite direction by refeeding and overfeeding. Among these were genes involved in lipogenesis (ACLY, ACACA, FASN, SCD), control of protein synthesis (4EBP1, 4EBP2), β-oxidation (CPT1B), and insulin resistance (PEDF, SPARC).


CONCLUSIONS
Metabolic genes involved in lipogenesis, protein synthesis, and insulin resistance are central in the transcriptional response of adipocytes to changes in caloric intake.
Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
Niclas
N
Franck
Anders
A
Gummesson
Margareta
M
Jernås
Camilla
C
Glad
Per-Arne
PA
Svensson
Gilles
G
Guillot
Mats
M
Rudemo
Fredrik H
FH
Nyström
Lena M S
LM
Carlsson
Bob
B
Olsson
D017667:Adipocytes / Q000502:physiology*; D000328:Adult; D001706:Biopsy; D001835:Body Weight / Q000235:genetics* / Q000502:physiology*; D031204:Caloric Restriction; D002149:Energy Intake / Q000235:genetics* / Q000502:physiology; D005136:Eye Proteins / Q000097:blood; D057140:Fast Foods; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007118:Immunoassay; D007333:Insulin Resistance / Q000235:genetics; D050155:Lipogenesis / Q000235:genetics; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood; D009765:Obesity / Q000178:diet therapy / Q000235:genetics; D010084:Oxidation-Reduction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000097:blood; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor