Neonatal and fetal exposure to trans-fatty acids retards early growth and adiposity while adversely affecting glucose in mice

Abstract

Industrially produced trans-fatty acids (TFAs) consumed in Western diets are incorporated into maternal and fetal tissues and are passed linearly to offspring via breast milk. We hypothesized that TFA exposure in utero and during lactation in infants would promote obesity and poor glycemic control as compared with unmodified fatty acids. We further hypothesized that in utero exposure alone may program for these outcomes in adulthood. To test this hypothesis, we fed female C57/BL6 mice identical Western diets that differed only in cis- or trans-isomers of C18:1 and then aimed to determine whether maternal transfer of TFAs through pregnancy and lactation alters growth, body composition, and glucose metabolism. Mice were unexposed, exposed during pregnancy, during lactation, or throughout pregnancy and lactation to TFA. Body weight and composition (by computed tomography) and glucose metabolism were assessed at weaning and adulthood. Trans-fatty acid exposure through breast milk caused significant early growth retardation (P < .001) and higher fasting glucose (P = .01), but insulin sensitivity was not different. Elevated plasma insulin-like growth factor-1 in mice consuming TFA-enriched milk (P = .02) may contribute to later catch-up growth and leanness and preserved peripheral insulin sensitivity observed in these mice. Mice exposed to TFA in utero underwent rapid early neonatal growth with TFA-free breast milk and had significantly impaired insulin sensitivity (P < .05) and greater abdominal fat (P = .01). We conclude that very early catch-up growth resulted in impaired peripheral insulin sensitivity in this model of diet-related fetal and neonatal programming. Trans-fatty acid surprisingly retarded growth and adiposity while still adversely affecting glucose metabolism.

Figure 1

Study design denoting the dietary type and timing of exposure to CIS (open arrows) and TRANS (grey arrows). Diets were initiated in sibling females at 6 weeks (n=8/group) with breeding attempts from 8 weeks of age. Only litters from primiparous females were evaluated (n= 5–7/group) with endpoints at weaning (day 21) and adulthood (day 60–70) made in offspring from all litters balanced by sex.

Figure 2

Growth of mice exposed to CIS diets during in utero and through breastfeeding during neonatal growth periods (CC; white bar), TRANS diet in utero and CIS diet during breastfeeding (TC; checked bar), CIS diet in utero and TRANS diet during breastfeeding (CT; grey bar) and TRANS diet during in utero and breastfeeding growth periods (TT; diagonal striped bar). Means ± SEM depicted with different letters denoting statistical differences at α < 0.05 following ANOVA with sample sizes of 15–29 for each group.

Figure 3

Body composition of offspring at weaning as measured by computed tomography and calculation of abdominal fat volume and converted to a weight/weight basis for each individual. Data shown represents means ± SEM of the groups, defined as CIS diets during in utero and through breastfeeding during neonatal growth periods (CC; white bar), TRANS diet in utero and CIS diet during breastfeeding (TC; checked bar), CIS diet in utero and TRANS diet during breastfeeding (CT; grey bar) and TRANS diet during in utero and breastfeeding growth periods (TT; diagonal striped bar). Two-way ANOVA analysis of diet exposure at each developmental stage was conducted and different letter superscripts denote statistical differences at α < 0.05 (n=10–18/group). A main effect of diet during lactation (CIS vs. TRANS) is present with TRANS exposure reducing adiposity.

Figure 4

A) Means ± SEM normalized glucose values from glucose tolerance testing of weanling mice (n=8–14/group) exposed to CIS diets during in utero and through breastfeeding during neonatal growth periods (CC; white bar), TRANS diet in utero and CIS diet during breastfeeding (TC; checked bar), CIS diet in utero and TRANS diet during breastfeeding (CT; grey bar) and TRANS diet during in utero and breastfeeding growth periods (TT; diagonal striped bar). The TC group demonstrates glucose intolerance and area under the curve calculated from this data series was significantly higher than all other groups (see Table 5). B) Means ± SEM normalized glucose values from insulin tolerance testing of weanling mice (n=6–11/group) from these same groups demonstrating further evidence that TC mice were significantly more insulin resistant (see Table 5) as determined by calculated areas under the curve.

Figure 4

A) Means ± SEM normalized glucose values from glucose tolerance testing of weanling mice (n=8–14/group) exposed to CIS diets during in utero and through breastfeeding during neonatal growth periods (CC; white bar), TRANS diet in utero and CIS diet during breastfeeding (TC; checked bar), CIS diet in utero and TRANS diet during breastfeeding (CT; grey bar) and TRANS diet during in utero and breastfeeding growth periods (TT; diagonal striped bar). The TC group demonstrates glucose intolerance and area under the curve calculated from this data series was significantly higher than all other groups (see Table 5). B) Means ± SEM normalized glucose values from insulin tolerance testing of weanling mice (n=6–11/group) from these same groups demonstrating further evidence that TC mice were significantly more insulin resistant (see Table 5) as determined by calculated areas under the curve.