Maternal obesity is necessary for programming effect of high-fat diet on offspring

Abstract

We tested the hypothesis that maternal consumption of dietary fat, independent from obesity, increases serum leptin in neonatal pups and predisposes them to adult obesity. Female rats either were fed a high-fat (HF) diet or a low-fat (LF) diet or were fed the HF diet but pair fed (PF) to the caloric intake of the LF group for 4 wk before breeding and throughout gestation and lactation. Dams consuming the HF diet had increased adiposity and were hyperphagic. At weaning, pups born to obese dams had significantly higher body fat and serum leptin levels and reduced insulin tolerance compared with offspring of LF-fed dams. Pups were weaned onto a chow diet until 8 wk of age, when they were then fed either HF or LF diet. At 18 wk of age, offspring from obese HF dams weighed more than offspring from nonobese LF or PF dams, and offspring eating HF diet weighed significantly more than those eating LF diet. Consequently, HF-fed offspring of obese HF dams weighed the most and LF-fed offspring from obese HF dams were similar in weight to HF-fed offspring from nonobese LF dams. These data suggest that maternal obesity exerts an independent effect on offspring body weight that is of similar magnitude as the effect of the offspring's adult diet. Furthermore, there was no difference in body weight between the nonobese LF and PF offspring on either diet. Together, these data suggest that maternal adiposity, and not dietary fat per se, induces hyperleptinemia and insulin resistance in offspring, as well as an increased body weight that persists into adulthood.

Fig. 1.

Body weight gain in dams before breeding, during gestation, and during lactation. Female Long-Evans rats were fed a high-fat (HF) diet or a low-fat (LF) diet or were pair fed to the caloric intake of the LF group for 4 wk and then bred, continuing on their respective diets throughout lactation. Data are expressed as mean ± SE body weights with 6 or 7 rats per group. *P < 0.05 compared with LF group. g, Gestation day; p, postpartum day.

Fig. 2.

Effect of HF diet on dams during lactation. Female Long-Evans rats were fed a HF diet or a LF diet or were pair fed (PF) to the caloric intake of the LF group for 4 wk and then bred, continuing on their respective diets throughout lactation. A: serum and milk were collected at postpartum day 7, and leptin levels were measured. Values are expressed as mean ± SE leptin values, with 3–6 animals per group. B: serum glucose was measured at weaning. Values are expressed as mean ± SE glucose values, with 3 or 4 animals per group. *Difference from LF group, P < 0.05.

Fig. 3.

Measures of adiposity from male offspring of dams fed HF or LF at weaning. Female Long-Evans rats were fed a HF diet or a LF diet or were pair fed (PF) to the caloric intake of the LF group for 4 wk and then bred, continuing on their respective diets throughout lactation. A: offspring body weight from birth until weaning of 26–34 animals per group. B: serum leptin levels measured at weaning of male offspring; 5 or 6 animals per group. C: weight of retroperitoneal fat pad expressed as mean ± SE % of body weight; 5 or 6 animals per group. D: mean ± SE % of body fat per gram of body weight measured via NMR at weaning; 22–25 animals per group. *Difference from LF group, P < 0.05.

Fig. 4.

Effect of maternal obesity on insulin sensitivity at weaning. An insulin tolerance test (ITT) was performed on offspring of obese dams fed HF or nonobese LF and PF dams after a 4-h fast. A: mean ± SE change in glucose levels of weanling rats after receiving 0.5 U/kg body mass of insulin; 9–12 animals per group. B: mean ± SE change (Δ) in area under ITT curve; 9–12 animals per group. *Difference from LF group, P < 0.05.

Fig. 5.

Effect of maternal obesity on offspring while eating a chow diet. A: mean ± SE body weight of offspring from obese HF-fed dams or nonobese LF or PF dams from 3 to 8 wk of age while eating chow. B: average ± SE daily food intake of these offspring during the 5 wk on chow. C: mean ± SE % of body fat per gram of body weight measured via NMR at 8 wk of age. There were 20 animals per group in A–C. D: mean ± SE 4-h fasted glucose at 8 wk of age; 10–12 animals per group. E: an ITT was performed after a 4-h fast at 8 wk of age. Mean ± SE change in area under the curve for the ITT is shown; 10–12 animals per group. *Difference from LF group, P < 0.05.

Fig. 6.

Effect of maternal obesity on body weight and food intake of adult offspring. Offspring of obese HF-fed dams or nonobese LF or PF dams were fed a HF or LF diet starting at 8 wk of age. A: body weight ± SE of the offspring from 8 to 18 wk of age, with 10 animals per group. LF-LF, PF-LF, pups born to nonobese LF or PF dams and consuming LF; HF-HF, pups born to obese HF dams and consuming HF; LF-HF, PF-HF, HF-LF, pups born to nonobese LF mothers and consuming HF in adulthood. B: main effects of maternal obesity. C: main effects of offspring diet. D: cumulative food intake of the offspring from 8 to 18 wk of age; 10 animals per group. *Significant main effect, P < 0.05.

Fig. 7.

Effect of maternal obesity on offspring adiposity. Offspring of obese HF-fed dams or nonobese LF or PF dams were fed a HF or LF diet starting at 8 wk of age. Body fat as % of body mass was measured at 8, 12, 15, and 18 wk of age. There were 10 animals per group, except for 20 animals in the 8-wk group.

Fig. 8.

Effect of maternal obesity on an intraperitoneal glucose tolerance test (IPGTT) performed at 20 wk of age on offspring from obese HF-fed dams and nonobese LF or PF dams. Rats were fasted overnight. Mean ± SE change in area under the curve for the IPGTT is shown; 4–6 animals per group.