Previous research has shown that prenatal diets rich in specific nutrients (e.g. taurine, omega-3 fatty acids) may provide protective cardiometabolic effects for adult offspring. The purpose of the current study was to investigate the potential of a prenatal-lactation diet rich in omega-3 long-chain polyunsaturated fatty acids (omega-3 LC PUFAs) to improve metabolic function in offspring fed a high saturated fat “Western” diet postweaning. We compared growth and metabolic biomarkers of three groups of Sprague Dawley rat offspring all weaned to a high saturated fat “Western” (Western) diet, but whose mothers were fed one of three different diets during pregnancy-lactation: 1) omega-3 “PUFA”-rich (PUFA/Western); 2) control (Control/Western); and 3) high saturated fat “Western” (Western/Western). PUFA/Western offspring had significantly lower fasting insulin (P < 0.01) and HOMA-IR (P < 0.01), and lower mean plasma triglycerides than Western/ Western animals. Additionally, mean HOMA-IR, fasting plasma insulin, and triglycerides were 19%, 10% and 14% lower, respectively, than those of Control/Western animals, although these differences were not statistically significant. Western/Western adult offspring had the highest fasting plasma insulin, triglycerides, and insulin-resistance (HOMA-IR) of the three groups. Our results indicated that a maternal omega-3 PUFA-rich diet during pregnancy-lactation may provide modest protective metabolic effects for adult offspring, even when consuming a high energy and saturated fat diet.
A large body of epidemiological and experimental animal research has shown that nutritional insults during pregnancy and lactation, including overnutrition, can deleteriously alter metabolic function in adult offspring [
The purpose of the current pilot study was to investigate the potential protective effect of a prenatal-lactation diet rich in omega-3 LC-PUFAs on metabolic function of adult offspring consuming a high saturated fat Western diet.
Male and female adult Sprague-Dawley breeders were obtained from Simonsen Laboratories, Inc. and housed in the University of Nevada, Las Vegas Animal Care Facility. Males and females were housed separately in plastic cages and were maintained on a control chow diet for 10 days while acclimatizing to the new environment (Ta- ble 1). On the 10th day female animals were randomly assigned to one of three test diets: PUFA, Western, or Control. The PUFA diet was custom formulated to model the “traditional” southwestern Alaskan Yup’ik Eskimo dietary intakes, a diet well known for its omega3/omega-6 balanced, high PUFA content [
Females were maintained on their assigned diet for seven days. During this time, both food and water were supplied ad libitum. On day 17, males and females on the same diet were combined and transferred to larger
F0 Generation | F1 Generation |
---|---|
Maternal Diets | Post-weaning Diets |
PUFA | Western |
Control | Western |
Western | Western |
Component | Control | PUFA | Western |
---|---|---|---|
Calories provided by | |||
Protein | 28.5% | 30.3% | 17.8% |
Fat | 13.5% | 59.8% | 29.8% |
Carbohydrate | 58.0% | 10.0% | 52.3% |
P:S | 1:1 | 2:1 | 0.5:1 |
Omega-6:Omega-3 | 6.5:1 | 1.5:1 | 9:1 |
plastic cages to begin breeding. Dams consuming the control diet were placed with a male breeder after the other two experimental dams became pregnant. Litters were standardized for size and sex within each prenatal diet group using cross-fostering and culling techniques when the pups were 10 days of age. Pups were fed their assigned postnatal diets at weaning (
Experimental diets differed in macronutrient composition, fat sources, and ratios of polyunsaturated to saturated fatty acids (
Plasma glucose and blood lipid concentrations were measured using the Abaxis Blood Chemistry Analyzer. Glycosylated hemoglobin (HbA1c) was measured using the Bayer DCA 2000 Chemistry Analyzer. ZRT Laboratories in Beaverton, Oregon, analyzed insulin by ELISA.
Kruskal-Wallis tests were used to examine differences in body weight/BMI, HbA1c, fasting plasma glucose, HOMA-IR, fasting plasma insulin, and triglycerides among the three experimental diet groups. Levene’s tests were performed to examine the homogeneity of variances. Bonferroni tests with Bonferroni correction and Dunnett’s T3 tests were used in post-hoc analyses for variables with equal and unequal variances, respectively. For body weight data, given a larger sample size, one-way ANOVA tests were used to examine differences in body weight among pre-weaning pups after data normality was confirmed. Data were analyzed using SPSS version 21.0 (IBM Corp., Armonk, NY). Descriptive statistics were used to detect potential outliers of which values were greater or less than mean ±1.65 standard deviations. The significance level was fixed at 0.05 for all statistical tests.
PUFA/Western offspring were significantly (P < 0.01) less insulin resistant (as measured by HOMA-IR) than Western/Western animals (
Biomarker | PUFA/Western | Control/Western | Western/Western | P-value* | Post-hoc Test | |||
---|---|---|---|---|---|---|---|---|
N | Mean ± S.E. | N | Mean ± S.E. | N | Mean ± S.E. | |||
BMI (g/cm2) | 4 | 0.60 ± 0.05 | 5 | 0.55 ± 0.03 | 3 | 0.60 ± 0.04 | 0.475 | |
Male | 2 | 0.67 ± 0.00 | 2 | 0.61 ± 0.01 | 2 | 0.65 ± 0.01 | ||
Female | 2 | 0.53 ± 0.06 | 3 | 0.51 ± 0.02 | 1 | 0.52 ± 0.00 | ||
HbA1c (%) | 4 | 3.43 ± 0.05 | 5 | 3.22 ± 0.05 | 3 | 3.37 ± 0.03 | 0.052 | |
Male | 2 | 3.50 ± 0.00 | 2 | 3.20 ± 0.00 | 2 | 3.40 ± 0.00 | ||
Female | 2 | 3.35 ± 0.05 | 3 | 3.23 ± 0.09 | 1 | 3.30 ± 0.00 | ||
Glucose (mmol/L) | 4 | 7.79 ± 0.17 | 5 | 8.78 ± 0.32 | 3 | 7.48 ± 0.27 | 0.024 | C/W > W/W† |
Male | 2 | 8.08 ± 0.08 | 2 | 8.39 ± 0.28 | 2 | 7.75 ± 0.03 | ||
Female | 2 | 7.50 ± 0.00 | 3 | 9.04 ± 0.48 | 1 | 6.94 ± 0.00 | ||
HOMA-IR | 4 | 0.95 ± 0.07 | 5 | 1.17 ± 0.10 | 3 | 2.07 ± 0.20 | 0.023 | W/W > P/W† |
Male | 2 | 1.04 ± 0.11 | 2 | 0.96 ± 0.03 | 2 | 2.27 ± 0.01 | ||
Female | 2 | 0.86 ± 0.00 | 3 | 1.32 ± 0.10 | 1 | 1.67 ± 0.00 | ||
Insulin (pmol/L) | 4 | 18.95 ± 1.12 | 5 | 20.95 ± 1.99 | 3 | 42.97 ± 2.76 | 0.025 | W/W > P/W‡ |
Male | 2 | 20.07 ± 2.25 | 2 | 17.82 ± 0.00 | 2 | 45.72 ± 0.42 | ||
Female | 2 | 17.82 ± 0.00 | 3 | 23.04 ± 2.78 | 1 | 37.47 ± 0.00 | ||
Triglycerides (mmol/L) | 4 | 0.66 ± 0.08 | 5 | 0.77 ± 0.08 | 3 | 0.83 ± 0.16 | 0.443 | |
Male | 2 | 0.64 ± 0.12 | 2 | 0.83 ± 0.03 | 2 | 0.86 ± 0.28 | ||
Female | 2 | 0.68 ± 0.15 | 3 | 0.74 ± 0.13 | 1 | 0.76 ± 0.00 |
*Kruskal-Wallis test; †Bonferroni test with Bonferroni correction; ‡Dunnett’s T3 test.
There were no significant differences in mean fasting plasma glucose between PUFA/Western animals and either Control/Western or Western/Western offspring. Mean fasting plasma glucose was significantly higher, however, among Control/Western animals than Western/Western offspring (P < 0.01). Longer-term, average blood glucose, as measured by HbA1c, varied minimally among the three groups, but was the highest among PUFA/Western animals, followed by Western/Western and Control/Western offspring.
The mean plasma triglyceride value of PUFA/Western animals (0.66 mmol/L) was 20% lower than that of Western/Western offspring (0.83 mmol/L). Mean triglycerides of Control/Western (0.77 mmol/L) were intermediate to those of the PUFA/Western and Western/Western groups, although these differences did not reach a 0.05 P-value for statistical significance.
There were no significant differences in body weights on day 7 among offspring whose mother consumed the PUFA, Western, or Control diets during pregnancy-lactation. By day 21, offspring whose mothers were fed a PUFA diet during pregnancy and lactation were significantly (P < 0.01) heavier compared to offspring whose mother consumed either a Western or Control diet (
Day | PUFA | Control | Western | P-value* | Post-hoc Test | |||||
---|---|---|---|---|---|---|---|---|---|---|
N | Mean ± S.E. | N | Mean ± S.E. | N | Mean ± S.E. | |||||
7 | 15 | 16.80 ± 1.13 | 18 | 17.20 ± 0.19 | 18 | 16.44 ± 0.48 | 0.700 | |||
21 | 15 | 54.31 ± 1.22 | 18 | 47.93 ± 0.61 | 18 | 51.64 ± 0.72 | 0.000 | P > C, W > C† | ||
*One-way ANOVA test; †Bonferroni test with Bonferroni correction.
Day | PUFA/Western | Control/Western | Western/Western | P-value* | Post-hoc Test | |||
---|---|---|---|---|---|---|---|---|
N | Mean ± S.E. | N | Mean ± S.E. | N | Mean ± S.E. | |||
25 | 4 | 65.73 ± 5.44 | 5 | 63.36 ± 1.42 | 3 | 69.83 ± 4.83 | 0.594 | |
49 | 4 | 205.35 ± 27.27 | 5 | 192.76 ± 14.83 | 3 | 217.47 ± 26.23 | 0.635 | |
63 | 4 | 258.13 ± 39.74 | 5 | 242.26 ± 24.95 | 3 | 277.63 ± 42.37 | 0.807 | |
70 | 4 | 280.10 ± 44.22 | 5 | 256.76 ± 28.17 | 3 | 296.83 ± 45.07 | 0.724 | |
81 | 4 | 303.35 ± 49.25 | 5 | 277.38 ± 33.62 | 3 | 321.80 ± 45.95 | 0.538 | |
109 | 4 | 336.10 ± 57.03 | 5 | 304.62 ± 41.27 | 3 | 370.57 ± 42.75 | 0.457 | |
120 | 4 | 338.95 ± 57.70 | 5 | 313.22 ± 44.14 | 3 | 370.93 ± 48.41 | 0.695 |
*Kruskal-Wallis test.
Previous experimental animal studies have shown diets rich in LC-PUFAs may play an important role in the developmental programming of growth and cardiometabolic function [
Our findings, showing a trend toward metabolic protection among offspring consuming an omega-3 PUFA-rich prenatal-lactation diet, and subsequently consuming a Western diet postweaning, are especially intriguing given that Yup’ik Alaskans, whose traditional diet is noted for its high omega-3 PUFA content, continue to have a low prevalence (3.3%) of type 2 diabetes [
The size of the current pilot study is an important limitation and our results should be interpreted with caution. Should our findings, which suggested that maternal prenatal-lactation diets rich in omega-3 PUFAs provide some metabolically protective effects for adult offspring, be confirmed by additional research, the public health potential of type 2 diabetes/metabolic syndrome primary prevention strategies based on this finding could be significant.
The authors would like to acknowledge the funding support provided by the UNLV Edwards and Olswang and the Rocchio research grants. We would also like to acknowledge the helpful contributions of Alyssa Crittenden and Celeste Giordano.