Korean J Physiol Pharmacol.  2021 Jan;25(1):39-49. 10.4196/kjpp.2021.25.1.39.

Ovariectomy, but not orchiectomy, exacerbates metabolic syndrome after maternal high-fructose intake in adult offspring

• Kim M
• Kim I

• KMID: 2509653
• DOI: http://doi.org/10.4196/kjpp.2021.25.1.39

Abstract

High fructose diet is associated with the global metabolic syndrome (MtS) pandemic. MtS develops in early life, depending on prenatal and postnatal nutritional status. We hypothesized that ovariectomy increases the chances of developing MtS in adult offspring following high fructose intake by the mother. Pregnant C57BL/6J mouse dams drank water with or without 20% fructose during pregnancy and lactation. After weaning, the pups were fed regular chow. The offspring were evaluated until they were 7 months of age after the mice in each group, both sexes, were gonadectomized at 4 weeks of age. The offspring (both sexes) of the dams who had high fructose intake developed MtS. In the offspring of dams who drank tap water, orchiectomy increased the body weight gain and body fat accumulation, while ovariectomy increased the body fat accumulation as compared to the sham controls. In the offspring of dams with high fructose intake, orchiectomy decreased the body weight gain, body fat accumulation, visceral adiposity, and glucose intolerance, while ovariectomy exacerbated all of them as compared to the sham operations. These data indicate that ovariectomy encourages the development of MtS in adult offspring after maternal high fructose intake, while orchiectomy prevents the development of MtS. The sex difference indicates that male and female sex hormones play contradictory roles in the development of MtS.

Keyword

Fructose; Metabolic syndrome; Orchiectomy; Ovariectomy; Sex difference

Figure

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  Fig. 1 Study design and effects of gonadectomy on maternal high fructose exposure induced weight gain. We randomly assigned 8-week-old pregnant C57BL/6J mice (F0) to groups provided with drinking water with or without 20% fructose over the course of the pregnancy and lactation periods. After weaning, the pups were fed regular chow. (A) Four-week-old mice were randomly divided into 8 groups and half of those in each group, both male and female, were gonadectomized. The mice were evaluated at 7 months of age. (B, C) Their body weights were measured every week. The graph shows intervals of 4 weeks. (D, E) Body weight in male and female mice at 28 weeks (+p < 0.05, control sham vs. control gonadectomy; *p < 0.05, control sham vs. fructose sham; #p < 0.05 and ##p < 0.01, fructose sham vs. fructose gonadectomy).

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  Fig. 2 Effect of gonadectomy on maternal high fructose exposure induced glucose intolerance. Glucose tolerance tests (GTT) were performed on male offspring at 7, 11, 16, and 28 weeks of age. (B) The corresponding area under the curve (AUC) value was obtained from (A). Maternal high fructose intake caused glucose intolerance. Orchiectomy suppressed glucose intolerance in the maternal fructose exposure group. Data are presented as mean ± standard error for six mice (*p < 0.05 and **p < 0.01, control sham vs. fructose sham; #p < 0.05, fructose sham vs. fructose gonadectomy).

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  Fig. 3 Effect of gonadectomy on maternal high fructose exposure induced glucose intolerance. (A) Glucose tolerance tests (GTT) were performed on female offspring at 7, 11, 16, and 28 weeks of age. (B) The corresponding area under the curve (AUC) value was obtained from (A). Maternal high fructose intake caused glucose intolerance. Ovariectomy promoted glucose intolerance in the maternal fructose-exposed group. Data are presented as mean ± standard error for 6 mice (#p < 0.05, fructose sham vs. fructose gonadectomy; *p < 0.05, control sham vs. fructose sham).

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  Fig. 4 Effects of gonadectomy on maternal high fructose exposure induced steatosis. Representative images of offspring livers are shown (each group, n = 6). Liver sections were stained with Oil Red O or H&E (bar = 50 μm, stain magnification ×100). Maternal high fructose intake induced steatosis.

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  Fig. 5 Effects of gonadectomy on maternal high fructose exposure induced lipogenesis in offspring livers. The expression of lipogenesis proteins was detected using Western blotting in male offspring (A) and female offspring (C). Maternal high fructose exposure increased the expression of lipogenesis in both the sexes. All the samples were run in the same condition. (B, D) Relative protein expression was quantified using optical densitometry (ImageJ software, http://rsbweb.nih.gov). The sample was obtained from mice liver (each group, n = 6). The graphs show the mean ± standard error for 3 independent experiments (*p < 0.05 and **p < 0.01, control sham vs. fructose sham; #p < 0.05 and ##p < 0.01, fructose sham vs. fructose gonadectomy).

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  Fig. 6 Effects of gonadectomy on maternal high fructose exposure increased fat mass. (A) Representative micro-computed tomography image of body fat mass at 28 weeks. Maternal high fructose exposure increased body fat. (B, C) Percentages of visceral adipose tissue (VAT) in male and female mice. Data are expressed as mean ± standard error for 6 mice (+p < 0.05, control sham vs. control gonadectomy; *p < 0.05, control sham vs. fructose sham; #p < 0.05, fructose sham vs. fructose gonadectomy).

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  Fig. 7 Effects of gonadectomy on maternal high fructose exposure increased adipocyte size. Representative images of white adipose tissue (WAT) in the offspring are shown (each group, n = 6) WAT sections were stained with H&E (A), and the adipocyte size was quantified using optical densitometry (ImageJ software, http://rsbweb.nih.gov) (B, C) (bar = 200 μm, stain magnification ×200) (**p < 0.01, control sham vs. fructose sham; ##p < 0.01, fructose sham vs. fructose gonadectomy).

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