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. 2015 Mar;10(2):4.
doi: 10.1007/s12263-015-0454-6. Epub 2015 Jan 20.

The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism

Adam Kretowski #  1   2 , Edyta Adamska #  2 , Katarzyna Maliszewska  1 , Natalia Wawrusiewicz-Kurylonek  1 , Anna Citko  1   2 , Joanna Goscik  3 , Witold Bauer  1   2 , Juliusz Wilk  1 , Anna Golonko  4 , Magdalena Waszczeniuk  1   4 , Danuta Lipinska  1 , Justyna Hryniewicka  1 , Magdalena Niemira  2 , Magdalena Paczkowska  2 , Michal Ciborowski  2 , Maria Gorska  1
Affiliations

The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism

Adam Kretowski et al. Genes Nutr. 2015 Mar.

Abstract

Large-scale meta-analyses of genome-wide association studies have recently confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is associated with fasting glycemia and type 2 diabetes mellitus; however, the mechanism of this link was not well established. The aim of our study was to evaluate the functional/phenotypic differences related to rs340874 PROX1 variants. The study group comprised 945 subjects of Polish origin (including 634 with BMI > 25) without previously known dysglycemia. We analyzed behavioral patterns (diet, physical activity), body fat distribution and glucose/fat metabolism after standardized meals and during the oral glucose tolerance test. We found that the carriers of the rs340874 PROX1 CC genotype had higher nonesterified fatty acids levels after high-fat meal (p = 0.035) and lower glucose oxidation (p = 0.014) after high-carbohydrate meal in comparison with subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we found higher accumulation of visceral fat (p < 0.02), but surprisingly lower daily food consumption (p < 0.001). We hypothesize that lipid metabolism alterations in subjects with the PROX1 CC genotype may be a primary cause of higher glucose levels after glucose load, since the fatty acids can inhibit insulin-stimulated glucose uptake by decreasing carbohydrate oxidation. Our observations suggest that the PROX1 variants have pleiotropic effect on disease pathways and it seem to be a very interesting goal of research on prevention of obesity and type 2 diabetes mellitus. The study may help to understand the mechanisms of visceral obesity and type 2 diabetes mellitus risk development.

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Figures

Fig. 1
Fig. 1
Glucose levels (a) and glucose oxidation (b) after high-carbohydrate meal intake by the rs340874 PROX1 genotype
Fig. 2
Fig. 2
NEFA levels (a) and fat oxidation (b) after high-fat meal intake by the rs340874 PROX1 genotype
See this image and copyright information in PMC

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