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Effects on metabolic markers are modified by PPARG2 and COX2 polymorphisms in infants randomized to fish oil.

ABSTRACT: Long-chain n-3 fatty acids (n-3 LCPUFA) improve blood pressure (BP) and lipid profile in adults and improve insulin sensitivity in rodents. We have previously shown that n-3 LCPUFA reduces BP and plasma triacylglycerol (TAG) in infants. Few studies have found effects on glucose homeostasis in humans. We explored possible effect modification by FADS, PPARG2, and COX2 genotypes to support potential effects of n-3 LCPUFA on metabolic markers in infants. Danish infants (133) were randomly allocated to daily supplementation with a teaspoon (~5 mL/day) of fish oil (FO) or sunflower oil (SO) from 9 to 18 months of age. Before and after the intervention, we assessed BP, erythrocyte n-3 LCPUFA, plasma lipid profile, insulin, and glucose in addition to functional single nucleotide polymorphisms in FADS, PPARG2, and COX2. At 18 months, plasma TAG was lower in the FO compared with SO group (p = 0.014). This effect was modified by PPARG2-Pro12Ala, as TAG only decreased among heterozygotes. FO supplemented PPARG2 Pro12Ala heterozygotes also had decreased plasma glucose compared with the SO group (p = 0.043). The effect of FO on mean arterial BP at 18 months was gender dependent (p = 0.020) and reduced in boys only (p = 0.028). Diastolic BP was, however, lower among all FO supplemented homozygous COX2-T8473C variant allele carriers compared with the SO group (p = 0.001). In conclusion, our results confirm that FO supplementation in late infancy reduces TAG and BP and indicates that the effects are mediated via peroxisome proliferator-activated receptor-? and cyclooxygenase-2. Furthermore, FO reduced plasma glucose only in PPARG2 heterozygotes.

SUBMITTER: Harslof LB

PROVIDER: S-EPMC4026428 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Effects on metabolic markers are modified by PPARG2 and COX2 polymorphisms in infants randomized to fish oil.

Harsløf Laurine B S LB Damsgaard Camilla T CT Hellgren Lars I LI Andersen Anders D AD Vogel Ulla U Lauritzen Lotte L

Genes & nutrition 20140319 3

Long-chain n-3 fatty acids (n-3 LCPUFA) improve blood pressure (BP) and lipid profile in adults and improve insulin sensitivity in rodents. We have previously shown that n-3 LCPUFA reduces BP and plasma triacylglycerol (TAG) in infants. Few studies have found effects on glucose homeostasis in humans. We explored possible effect modification by FADS, PPARG2, and COX2 genotypes to support potential effects of n-3 LCPUFA on metabolic markers in infants. Danish infants (133) were randomly allocated ...[more]

PMID: 24643342

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Project description:High protein intake in early life is associated with an increased risk of childhood obesity. Dietary protein intake may be a key mechanistic modulator through alterations in endocrine and metabolic responses. We aimed to determine the impact of different protein intake of infants on blood metabolic and hormonal markers at the age of four months. We further aimed to investigate the association between these markers and anthropometric parameters and body composition until the age of two years. Term infants received a modified low-protein formula (mLP) (1.7 g protein/100 kcal) or a specifically designed control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double blinded RCT. The outcomes were compared with a breast-fed (BF) group. Glucose, insulin, leptin, IGF-1, IGF-BP1, -BP2, and -BP3 levels were measured at the age of 4 months. Anthropometric parameters and body composition were assessed until the age of 2 years. Groups were compared using linear regression analysis. No significant differences were observed in any of the blood parameters between the formula groups (n = 53 mLP; n = 44 CTRL) despite a significant difference in protein intake. Insulin and HOMA-IR were higher in both formula groups compared to the BF group (n = 36) (p < 0.001). IGF-BP1 was lower in both formula groups compared to the BF group (p < 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group (p < 0.01) and a higher IGF-BP3 level in the mLP group compared to the BF group (p = 0.03). There were no significant differences in glucose, leptin, and IGF-1 between the three feeding groups. We found specific associations of all early-life metabolic and hormonal blood parameters with long-term growth and body composition except for IGF-1. Reducing protein intake by 20% did not result in a different metabolic profile in formula-fed infants at 4 months of age. Formula-fed infants had a lower insulin sensitivity compared to breast-fed infants. We found associations between all metabolic and hormonal markers (except for IGF-1) determined at age 4 months and growth and body composition up to two years of age.

Project description:BackgroundPrevious intervention studies have reported the association of the PPARG2 Pro12Ala (rs1801282) and IL6 -174G > C (rs1800795) polymorphisms with weight loss; however, their results are inconsistent. We aimed to investigate the effect of the PPARG2 Pro12Ala and IL6 -174G > C polymorphisms on body weight, body composition and metabolic parameters after a 12-week nutritional intervention with a traditional Brazilian diet and extra virgin olive oil supplementation in severely obese patients.MethodsA total of 149 severely obese individuals [body mass index (BMI) ≥ 35 kg/m2] were randomized into three 12-week nutritional intervention groups - the extra virgin olive oil supplementation (OO) group (n = 50), the traditional Brazilian diet (DieTBra) group (n = 49), and the DieTBra plus extra virgin olive oil supplementation (DieTBra+OO) group (n = 50). Anthropometric measurements, body composition, metabolic parameters, physical activity practise and dietary intake were assessed. The associations were tested using generalized linear models adjusted for confounders.ResultsThe PPARG2 Pro12Ala polymorphism influenced body composition changes. Ala carriers in the intervention groups with extra virgin olive oil supplementation had greater reductions in the percentage of body fat (%BF) (OO: p = 0.049, DietBra+OO: p = 0.004) and greater increases in both fat-free mass (FFM) (OO: p = 0.020, DieTBra: p = 0.007) and lean mass (LM) (OO: p = 0.020, DieTBra+OO: p = 0.007) than did ProPro homozygotes. No association was found for the IL6 -174G > C polymorphism.ConclusionsExtra virgin olive oil intake may modulate favourable body composition changes, promoting a decrease in the %BF and increases in the LM and FFM of severely obese individuals, even without weight loss, in the presence of the Ala allele of the Pro12Ala polymorphism.Trial registrationRegistered under ClinicalTrials.gov Identifier No. NCT02463435.

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Effects on metabolic markers are modified by PPARG2 and COX2 polymorphisms in infants randomized to fish oil.

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Effects on metabolic markers are modified by PPARG2 and COX2 polymorphisms in infants randomized to fish oil.

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