Nutr Res Pract.  2021 Apr;15(2):160-172. 10.4162/nrp.2021.15.2.160.

Maternal high-fructose intake during pregnancy and lactation induces metabolic syndrome in adult offspring

• Koo S
• Kim M
• Cho HM
• Kim I

• KMID: 2514438
• DOI: http://doi.org/10.4162/nrp.2021.15.2.160

Abstract

BACKGROUND/OBJECTIVES
Nutritional status and food intake during pregnancy and lactation can affect fetal programming. In the current metabolic syndrome epidemic, highfructose diets have been strongly implicated. This study investigated the effect of maternal high-fructose intake during pregnancy and lactation on the development of metabolic syndrome in adult offspring.
SUBJECTS/METHODS
Drinking water with or without 20% fructose was administered to female C57BL/6J mice over the course of their pregnancy and lactation periods. After weaning, pups ate regular chow. Accu-Chek Performa was used to measure glucose levels, and a tail-cuff method was used to examine systolic blood pressure. Animals were sacrificed at 7 months, their livers were excised, and sections were stained with Oil Red O and hematoxylin and eosin (H&E) staining. Kidneys were collected for gene expression analysis using quantitative real-time Polymerase chain reaction.
RESULTS
Adult offspring exposed to maternal high-fructose intake during pregnancy and lactation presented with heavier body weights, fattier livers, and broader areas under the curve in glucose tolerance test values than control offspring. Serum levels of alanine aminotransferase, aspartate aminotransferase, glucose, triglycerides, and total cholesterol and systolic blood pressure in the maternal high-fructose group were higher than that in controls. However, there were no significant differences in mRNA expressions of reninangiotensin-aldosterone system genes and sodium transporter genes.
CONCLUSIONS
These results suggest that maternal high-fructose intake during pregnancy and lactation induces metabolic syndrome with hyperglycemia, hypertension, and dyslipidemia in adult offspring.

Keyword

Dyslipidemia; hypercholesterolemia; hyperglycemia; hypertension

Figure

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  Fig. 1 Effects of maternal high-fructose intake on body weight and liver size. The representative pictures of female and male offspring at 7 months of age. Dams were fed drinking water, either with or without 20% fructose. Offspring were fed chow diets and drunken tepid water after weaning. (A) Photographs of representative mice of each group after 7 months. Photograph of visceral fat and liver in offspring. (B) Body weight at 7 months of offspring. Data are presented as mean ± SE (n = 8). Statistical analyses were conducted using 2-way analysis of variance, followed by Tukey's post hoc tests for multiple comparisons (*P < 0.05, control vs. fructose).

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  Fig. 2 Effects of maternal high-fructose intake on fatty liver development. (A) Representative microscopic images of livers from female and male offspring at 7 months. Liver sections were stained with Oil Red O or H&E (bar = 50 μm, 100× magnification). (B) Hepatic TG level was measured by colorimetric method using TG quantification kit. Data are presented as mean ± SE of 6 mice in each group.TG, triglyceride; H&E, hematoxylin and eosin.Statistical analyses were conducted using 2-way analysis of variance, followed by Tukey's post hoc tests for multiple comparisons (**P < 0.01, control vs. fructose).

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  Fig. 3 Effects of maternal high-fructose intake on lipid metabolism in liver. (A, B) The expression of lipogenesis proteins was detected by western blotting in female and male offspring. Maternal high-fructose exposure increased the expression of lipogenesis in both gender. The gel is representative of 3 independent experiments. Glyceraldehyde-3-phosphate dehydrogenase expression was used as control. (C) Densitometry analysis of expressed ACC, FAS, SCD1, and SREBP using ImageJ program and normalized by the control level.Statistical analyses were conducted using 2-way analysis of variance, followed by Tukey's post hoc tests for multiple comparisons (*P < 0.05, **P < 0.01, control vs. fructose. ## P < 0.01, between female and male controls).

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  Fig. 4 Effects of maternal high-fructose intake on glucose tolerance. (A) GTTs were performed on female and male offspring at 7 months. Statistical analyses were conducted using Student's t-test. (B) Corresponding AUC values were obtained (A). Maternal high-fructose intake was strongly associated with glucose intolerance. (C) Glycated HbA1c was measured by colorimetric method using HbA1c Assay Kit.GTT, glucose tolerance test; AUC, area under the curve; HbA1c, hemoglobin A1c.Statistical analyses were conducted using 2-way analysis of variance, followed by Tukey's post hoc tests for multiple comparisons. Data are presented as mean ± SE of 8 mice in each group (*P < 0.05, **P < 0.01, control vs. fructose).

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  Fig. 5 Maternal high-fructose intake induced hypertension. (A) SBP was measured using a tail-cuff method in female and male mice at 7 months. Maternal high-fructose intake induced hypertension. (B-D) Serum renin, angiotensin II, and aldosterone (renin; expressed as ng/mL of the serum) were measured using enzyme-linked immunosorbent assay. Data are presented as mean ± SE of 6 mice in each group.SBP, systolic blood pressure.Statistical analyses were conducted using 2-way analysis of variance, followed by Tukey's post hoc tests for multiple comparisons (*P < 0.05, control vs. fructose).

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  Fig. 6 Effects of maternal high-fructose intake on the expression of oxidant enzyme and antioxidant enzyme genes in offspring kidneys. Expression of oxidant enzyme genes such as (A) Cyba, (B) Cybb, and (C) Nox4 in the kidney was quantified using qPCR. Expression of antioxidant enzyme genes such as (D) Sod1 and (E) Cat in the kidney was quantified using qPCR. Data are presented as mean ± SE of 6 mice in each group.qPCR, quantitative polymerase chain reaction.Statistical analyses were conducted using 2-way analysis of variance, followed by Tukey's post hoc tests for multiple comparisons (*P < 0.05, control vs. fructose. ## P < 0.01, between female and male controls).

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