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45: Accelerated aging in the offspring of mothers with pre-pregnancy obesity in a mouse model of developmental programming of metabolic syndrome

      Objective

      Obesity and metabolic syndrome are associated with acceleration of the aging process, characterized by shorter telomeres and low expression of Klotho gene. The objective of this was to determine if similar features are present in an established mouse model of developmental programming of metabolic syndrome, characterized by insulin resistance, obesity, hypertension and hyperlidemia.

      Study Design

      We utilized an established mouse model where, over 3 months, the dams are fed either high fat diet (34.9% fat, HF group) or standard chow (5.8% fat, SF group). After weaning, offspring from both groups were put on standard chow until sacrifice at 6 months of age. Visceral adipose tissue (VAT) and kidneys were obtained (n = 5-6 per group). Telomere relative length (TRL) was measured using genomic DNA analysis and quantitative real time PCR. Protein expression of Klotho was assessed by Western blot. Statistical analysis was performed using Student t- or Mann-Whitney test as appropriate (significance p<0.05).

      Results

      TRL in VAT was shorter in both HF female (HF 0.6 ± 0.1 vs SF 1.5 ± 0.4; p=0.02) and male (HF 0.4 ± 0.2 vs SF 0.8 ± 0.2; p=0.25) offspring compared to SF offspring. In kidneys TRL was higher in both HF male (HF 2.4 ± 0.3 vs SF 0.9 ± 0.1, p=0.004) and female (HF 1.8 ± 0.3 vs SF 1.0 ± 0.1; p=0.03) offspring. In contrary, in kidneys Klotho gene was significantly lower from HF males (HF 0.1 ± 0.04 vs SF 0.3 ± 0.1; p=0.03) and females (HF 0.09 ± 0.03 vs 0.5 ± 0.1; p=0.02) compared to SF (Figure).

      Conclusion

      Offspring born to obese mice demonstrate an accelerated aging process. These modifications were tissue- specific. Our data demonstrates for the first time that maternal pre-pregnancy obesity resulting from high fat diet programs the offspring for the development of accelerated aging.
      Figure thumbnail fx1
      Box plot: median, 25th-ile, 75th-ile, max and min values. *p<0.05. SF: pups born to mothers fed standard chow, HF: pups born to mothers fed high fat diet.