Genetic Variation in the Peroxisome Proliferator-Activated Receptor-γ2 Gene (Pro12Ala) Affects Metabolic Responses to Weight Loss and Subsequent Weight Regain

Barbara J. Nicklas, Elisabeth F.C. Van Rossum, Dora M. Berman, Alice S. Ryan, Karen E. Dennis, Alan R. Shuldiner

Research output: Contribution to journalArticle

102 Scopus citations


This study determined the effects of the peroxisome proliferator-activated receptor (PPAR)-γ2 Pro12Ala variant on body composition and metabolism and the magnitude of weight regain in 70 postmenopausal women (BMI 25-40 kg/m2) who completed 6 months of a hypocaloric diet. At baseline, BMI, percent body fat, intra-abdominal and subcutaneous abdominal fat areas, resting metabolic rate, substrate oxidation, and post-prandial glucose and insulin responses were not different between genotypes (Pro/Pro = 56, Pro/Ala and Ala/Ala = 14). The intervention similarly decreased body weight by 8 ± 1% in women homozygous for the Pro allele and by 7 ± 1% in women with the Ala allele (P < 0.0001). Fat oxidation did not change in Pro/Pro women but decreased 19 ± 9% in women with the Ala allele (P < 0.05). Changes in glucose area were not different between groups; however, women with the Ala allele decreased their insulin area more than women homozygous for the Pro allele (P < 0.05). Weight regain during follow-up was greater in women with the Ala allele than women homozygous for the Pro allele (5.4 ± 0.9 vs. 2.8 ± 0.4 kg, P < 0.01). PPAR-γ2 genotype was the best predictor of weight regain (r = 0.50, P < 0.01), followed by the change in fat oxidation (partial r = 0.35, P < 0.05; cumulative r = 0.58). Thus, the Pro12Ala variant of the PPAR-γ2 gene may influence susceptibility for obesity.

Original languageEnglish (US)
Pages (from-to)2172-2176
Number of pages5
Issue number9
StatePublished - Sep 2001
Externally publishedYes


ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this