Enhanced short-term improvement of insulin response to a low-caloric diet in obese carriers the Gly482Ser variant of the PGC-1alpha gene.
OBJECTIVE
The Gly482Ser missense mutation of the transcriptional coactivator, peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) has been involved in insulin function impairments, with conflicting results. The current study investigated the relationships of carrying this polymorphism with insulin resistance (IR) during a short-term weight-loss and the subsequent weight follow-up.


METHODS
The Gly482Ser was genotyped in 180 Spanish volunteers [body mass index: 31.4+/-3.2kg/m(2); age: 35+/-5 years]. Specific phenotypical measurements were determined at baseline, following an 8-week low-calorie diet (LCD) as well as after 6-month and 1-year of follow-up.


RESULTS
At baseline the Ser482Ser genotype was associated with higher HOMA-IR and insulin concentrations than the other genotypes (p<0.05), which was accompanied by an increased higher risk of IR (OR: 2.97; 95% CI: 1.24-7.15). After following the LCD, such increased risk of insulin insensitivity in Ser482Ser carriers was toned down (p>0.05). This outcome was sustained after 6-month and 1-year of follow-up (p>0.05).


CONCLUSIONS
These data show an increased risk of IR in obese carrying the rs8192673 Ser482Ser genotype. This risk was markedly reduced by an energy-restricted diet, which was sustained 6 months and 1 year after the diet therapy. This observation allows identifying obese subjects who might personally profit most from an energy-restrictive treatment concerning insulin response and lead to more individualized prognostic and therapeutic decisions.
Goyenechea
Estibaliz
E
Department of Nutrition and Food Science, Physiology and Toxicology, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
Crujeiras
Ana B
AB
Abete
Itziar
I
Parra
Dolores
D
Martínez
J Alfredo
JA
D000328:Adult; D050528:Diet, Carbohydrate-Restricted / Q000379:methods*; D005260:Female; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D009765:Obesity / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015431:Weight Loss / Q000235:genetics
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors