（HP 戦略研究・若手大学院奨励研究報告）

Effect of maternal glucoraphanin intake on chronic inflammation in thehypothalamus, cerebrum, and liver of high fructose-diet-fed rat offspring
exposed to maternal undernutrition
Anishma Karmacharya＊
Graduate School of Health Sciences, Aomori University of Health and Welfare
1 Glucoraphanin, ○2 Fructose, ○3 Lipid, ○4 Glucose, ○5 Maternal undernutrition
Key words ○Ⅰ．Background
The fetal and neonatal environment is associated with subsequent development of diseases in adulthood (1).
Maternal undernutrition during pregnancy and lactation can cause dyslipidemia, hyperglycemia which canaffect different organs and cause metabolic disorders such as chronic liver disease, Type 2 diabetes, andhypertension in offspring during their adulthood (2, 3).
Fructose, a simple monosaccharide, is used as a sweetener in food and drinks. High dietary fructose is amajor contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions (4).
Glucoraphanin (GR) derived from broccoli, is a water soluble, relatively inert precursor ofsulforaphane; the reactive isothiocyanate which has shown to be effective in different metabolic disorders
such obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD)(5). However, less is known
about the effect of GR intake during lactation on the lipid and glucose metabolism in the adult rat offspring
programmed by maternal protein restriction.
Ⅱ．Objectives
The aim of the present study was to explore the effect of maternal intake of GR-containing broccoli powder(BP) during lactation on lipid and glucose metabolism of high-fructose-diet fed male rat adult offspringborn from dams with low or normal protein diets.
Ⅲ．Materials and Methods
The Animal Research Committee, Aomori University of Health and Welfare, approved this study and all
experimental procedures were performed in accordance with the Institutional Guidelines for Animal
Experimentation (Permission number: 21008). Pregnant rats received diets containing 20 % (NormalProtein; NP) or 8 % (Low Protein; LP) casein. While 0 or 0.74% BP containing NP diets (NP/NP or NP/NP+BP) in Experiment (Expt.) 1 and 0 or 0.74% BP containing LP diets (LP/LP or LP/LP+BP in Expt. 2
were provided during lactation. At weaning, pups that received a diet of distilled water (W) or 10% fructose
solution (Fr) were divided into six groups: NP/NP/W, NP/NP/Fr, NP/NPBP/Fr in Expt. 1 and LP/LP/W,
LP/LP/Fr, LP/ LPBP /Fr in Expt. 2. The body weights, food intake, and water and fructose intake of pups
post weaning (PW) were recorded. At week 13 after treatment, male pups were weighed, and blood samples
were taken. The livers and adipose tissues (Epididymal Fat tissue; EFT and Perirenal Fat tissue PFT) weredissected and weighed. Glucose (Glc), triglyceride (TG), aspartate transaminase (AST), and alaninetransaminase (ALT) in the plasma levels and hepatic TG levels were measured.
Ⅳ．Results and Discussion
1. Body weights
During gestation, the body weights of dams in NP and LP groups didn’t differ significantly. During＊

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lactation, there was no significant difference in the body weights of male pups per litter between NP/NPand NP/NPBP groups in Expt. 1, and between LP/LP and LP/LPBP groups in Expt. 2, respectively. Afterweaning, there were no significant differences in the body weights of between BP and Fr groups in bothExpt. 1 and Expt. 2.
2. Food, water, and fructose intake
After weaning, the daily food intake of NP/NP/Fr was significantly lower than that of NP/NP/W group at
all PW weeks. While it was higher in NP/NPBP/Fr than NP/NP/Fr group in PW 8 and 10 weeks in Expt.1.
Similarly, the daily food intake was seen to be lower in LP/LP/Fr compared to LP/LP/W in PW8, 10, and12 weeks while it was higher in LP/LPBP/Fr than LP/LP/Fr in PW8 in Expt. 2. In Expt. 1, the fructose
intake was higher in NP/NP/Fr compared to NP/NP/W group in all PW weeks while it was higher inNP/NPBP/Fr than NP/NP/Fr in PW8 and PW12 week. Similarly in Expt. 2, the fructose intake was higherin LP/LP/Fr compared to LP/LP/W in PW8, 10, and 12 weeks while higher between LP/LPBP/Fr andLP/LP/Fr in PW5 weeks
3. Organ weights and hepatic function
The relative weight of livers and PFT were found to be higher in NP/NP/Fr group compared to NP/NP/W
group in Expt. 1. However, no significant differences were found between BP and Fr groups in Expt.1. InExpt.2, the relative weight of livers was found to be decreased in LP/LPBP/Fr compared to LP/LP/Fr. No
statistical significance was observed with weights of other organs in these groups.
The plasma AST and ALT level in LP/LPBP/Fr were lower than those in LP/LP/Fr. However, nosignificant differences in AST and ALT level were found among the three groups in Expt.1.
4. Effect of BP intake during lactation on plasma Glc and TG contents and hepatic content.
The plasma Glc and TG levels in NP/NP/Fr and NP/NPBP/Fr were significantly higher than that NP/NP/W.
No significant differences were observed between NP/NP/Fr and NP/NPBP/Fr in Expt. 1. Likewise, theplasma Glc and TG levels in LP/LP/Fr and LP/LPBP/Fr were significantly higher than those in LP/LP/W inExpt. 2. There was no significant difference in the Glc levels between LP/LP/Fr and LP/LPBP/Fr, whereas
the plasma TG levels in LP/LPBP/Fr were significantly lower than that in LP/LP/Fr. Although hepatic TG
levels were observed to be higher in BP groups compared to Fr groups, they were not found to bestatistically significant in both Expt.1 and Expt. 2, respectively.
V. Conclusion
Maternal BP intake during lactation may be involved in the alterations in weights of liver, adipose tissue aswell as lipid, glucose metabolism, and liver function parameters of adult male offspring fed on highfructose diet.
VI. References
1. Barker DJ et al. Nat Clin Pract Nephrol. 2006;2:700-7.
2. Bol VV et al. Obesity (Silver Spring). 2008;16:2760-3.
3. Lillycrop KA et al. J Nutr. 2005;135:1382.
4. Zhang DM et al. Nutrients. 2017;9:335
5. Du K et al. Sci Rep. 2021 Apr 8;11(1):7804.
VII. Presentation
Karmacharya A, et al. Effect of maternal glucoraphanin intake on lipid and glucose metabolism in highfructose-fed male rat offspring exposed to maternal protein restriction. 2022 年度青森県保健医療福祉研究発
表会, 2022 年 12 月, 青森市