Summary of Study “Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS-55) on adiposity and hepatic lipid consumption in rat offspring”

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For your information a study entitled “Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS-55) on adiposity and hepatic lipid consumption in rat offspring” was recently published in The Journal of Physiology. The study has garnered some attention resulting in a commentary in The Journal of Physiology entitled “Maternal fructose consumption can affect offspring metabolic outcomes” as well as a short commentary in Nursing Standard.

Researchers mated 90 virgin female and 15 male albino Wistar rats to produce enough pups for seven experimental groups. The female dams were acclimated with a one week ad libitum standard chow diet and water. After one week, the dams were randomly assigned to receive the control chow diet with ad libitum access to water (n=25), 10% w/v sucrose (n=19), or high fructose corn syrup (HFCS55, n=17). Dams remained on this diet for 4 weeks before breeding and throughout pregnancy and lactation. Within 24 hours of birth, litters were standardized to eight pups per litter (4 males and 4 females when possible). Pups were cross-fostered to achieve the seven experimental groups as described below:

  1. Offspring exposed to a  maternal control diet during both the prenatal and suckling periods (C-C; n = 8 litters)
  2. Offspring exposed to a maternal sucrose diet during both the prenatal and suckling periods (S-S; n = 11 litters)
  3. Offspring exposed to a maternal sucrose diet during the prenatal period then a maternal control diet during the suckling period (S-C; n = 8 litters)
  4. Offspring exposed to a maternal control diet during the prenatal period then a maternal sucrose diet during the suckling period (C-S; n = 8 litters)
  5. Offspring exposed to a maternal HFCS-55 diet during both the prenatal and suckling periods (H-H; n = 8 litters)
  6. Offspring exposed to a maternal HFCS-55 diet during the prenatal period then a maternal control diet during the suckling period (H-C; n = 9 litters)
  7. Offspring exposed to a maternal control diet during the prenatal period then a maternal HFCS-55 diet during the suckling period (C-H; n = 9 litters)

At 3 weeks, two males and two females from each experimental group were weaned onto a control diet consisting of standard chow and water. An intraperitoneal glucose tolerance test (IPGTT) was conducted on one male and one female pup per litter one day prior to sacrifice at 3 weeks. At 12 weeks, a second IPGTT test was conducted on the remaining weaned pups and blood and organ samples were collected.

Researchers report the following results:

  • Sucrose results:
    • No effect of prenatal and/or postnatal sucrose exposure on body weight, nose-tail length, or abdominal circumference at 3 or 12 weeks.
    • Female rats on S-C diets had lower relative heart weight compared to S-S but were comparable to C-C offspring at 3 weeks. At 12-weeks relative heart weight was lower in both S-C and C-S females compared to C-C females. Male rats showed no significant differences.
    • The relative pancreas weights were significantly lower in male S-S and C-S males compared to male C-C offspring at 12 weeks.
    • There were no effects of sucrose on relative liver, adrenal, or kidney weights in male or female rats at 3 or 12 weeks.
    • o   Sucrose exposure in the suckling period (C-S) was associated with greater visceral adipose tissue mass in females but not males at 3 weeks of age when compared to C-C.
      • This was difference was not maintained at 12 weeks.
    • Female rats exposed to sucrose during the prenatal period only (S-C) had significantly lower retroperitoneal adipose tissue mass compared to the C-C offspring at 12 weeks.
    • Male rats exposed to sucrose during the suckling period alone (C-S) had a lower relative total fat and total visceral fat mass and reduced relative gonadal and omental fat mass at 12 weeks compared to C-C off spring.
    • There were no effects of prenatal or postnatal sucrose exposure on glucose tolerance AUC in offspring at 3 weeks or 12 weeks. Moreover, there were no effects of sucrose exposure on individual blood glucose values during the glucose tolerance tests.
    • At 3 weeks, male and female S-S mice had lower plasma glucose compared to C-C.
    • HDL cholesterol and HDL:LDL cholesterol ratio were increased in S-C offspring compared to C-S offspring for both males and females
    • Plasma TG was higher at 3 weeks in C-S males compared to other sucralose groups but was not different from the control.
    • Plasma FFAs were increase in male S-C offspring compared to C-C. There were no differences in plasma FFAs at 3 weeks.
    • There were no other effects of perinatal sucrose on plasma hormones, metabolites, or lipids at 3 or 12 weeks.
    • There were no effects of perinatal sucrose exposure on total hepatic fat content or hepatic TG, FFA, or phospholipids at 3 weeks of age.
    • At 12 weeks, liver fat was higher in female offspring treated with sucrose. This was not the case for males. At 12 weeks, liver phospholipid concentration was higher for male rats treated with sucrose. This was not the case for females. However, Bonferroni post-hoc adjustment failed to identify any significant differences between treatment groups.
    • At 3 weeks, hepatic MUFA was increase in female S-S compared to C-C.
      • N-7 MUFA was higher in male and female S-S offspring compared to C-C offspring.
      • N-7 MUFA was higher in C-S compared to C-C females as well.
      • N-9 MUFA was higher in S-S compared to C-C females only.
      • N-3 PUFA was higher in S-C females compared to C-C and C-S groups.
    • There was no effect of sucrose on hepatic SFA or n-6 PUFA content at 3 weeks.
    • At 12 weeks, all individual fatty acids were comparable between groups.
  • HFCS-55 results:
    • There were no effects of perinatal HFCS-55 on offspring body weight, nose-tail length, or abdominal circumference.
    • Female H-H rats had a higher relative liver weight compared to both C-C and C-H offspring, this was not seen in males.
    • Relative organ weights were unaffected by HFSC-55 treatment.
    • At 3 weeks, plasma FFA concentrations ere high in H-C compared to C-C for males and females. This was also observed at 12 weeks.
    • There were no effects of perinatal HFCS-55 exposure on plasma glucose, leptin or TG concentrations.
    • Plasma LDL cholesterol was decreased in male and female H-H and H-C offspring compared to C-C, accompanied by an increase in HDL:LDL ratio.
    • At 3 weeks, HDL and HDL:LDL cholesterol were lower in C-H males when compared to all other groups. HDL and HDL:LDL were also lower in C-H females compared to H-H and C-H but were comparable to C-C.  At 12 weeks, C-H female offspring had higher HDL compared to C-C.
    • At 3 weeks C-H females had higher MUFA than C-C females.
      • Female C-H offspring also had increased n-9 MUFA compared to C-C females.
    • At 12 weeks there was no significant changes in total hepatic lipid content nor the content of any of the individual fatty acids.

Researchers conclude “perinatal exposure to maternal consumption of sucrose or HFCS-55 appears to have some detrimental effects on the offspring, particularly on adiposity, plasma FFAs and hepatic lipid composition, which differed depending on the sugar and the window of exposure… Maternal consumption of fructose-containing sugars appears to negatively affect long-term programming of offspring in a rodent model, and further research is required to better understand these programmed changes and their potential implications on the capacity of the offspring to adapt to a secondary metabolic challenge in postnatal life. Importantly, our results indicate that exposure to sucrose and HFCS-55 through the mothers diet, i.e., without direct consumption, is sufficient to produce negative impacts on metabolic health in the offspring. While we acknowledge the limitations of translating this research to humans, the results presented here suggest that limiting maternal consumption of added sugars may improve the short- and long-term metabolic health of the offspring.”

The commentary in The Journal of Physiology concludes “While these results cannot be directly translated to humans, they strongly suggest that controlling maternal consumption of added fructose may have a positive impact on the short- and long-term metabolic health of the offspring.”