If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Oral Plenary I Thursday, February 14 • 8:15 AM - 10:15 AM • Augustus Ballroom • Caesars Palace|
Volume 220, ISSUE 1, SUPPLEMENT , S3-S4, January 01, 2019
We, as well as others, have shown that maternal intake of high fructose has been shown to lead to sex- specific fetal programming of adult obesity, hypertension and metabolic dysfunction in mice. Our objective was to test the hypothesis that these outcomes are related to altered fructose metabolism, lipid accumulation and inflammation in the liver of adult offspring.
Study Design
Pregnant C57BL/6J dams were randomly allocated to fructose solution (10% W/V; n=10) as only drinking liquid or water (n=10), starting at ED 1 and until birth. After weaning, pups were then started on regular chow. Offspring were sacrificed when they reached adult stage (1 year of life) and their liver harvested. Protein and mRNA levels of ketohexokinase (KHK; a crucial enzyme in fructose metabolism that promotes insulin resistance and hepatic inflammation through toll like receptor-4: TLR-4), of transcription factors that lead to hepatic lipid accumulation (CHREBP: carbohydrate responsive element-binding protein; SREBP-1c: sterol regulatory element-binding protein-1c; PPAR-g: peroxisome proliferator-activated receptors-gamma), and of an enzyme responsible for tissue fat entrapment (CD36: fatty acid translocase) were assayed using Western blotting and PCR techniques. Normality was tested using Kurtosis. T-test or Mann-Whitney rank sum were used for statistical analysis. P< 0.05 was considered significant.Data are reported as mean ± SEM or median [IQR].
Results
Female adult mice born to dams in the fructose group had significantly higher liver CHREBP, SREBP-1c & KHK protein levels compared to controls (Figure 1A). No significant differences were noted in the male counterparts (Figure 1B). Despite lack of significant changes in liver protein levels of CD36 and PPAR-g, exposure to fructose was associated with upregulation of CD36, KHK & TLR-4 mRNA in females (Figure 2 A, B & C), and PPAR-g mRNA in males (Figure 2 D).
Conclusion
Exposure to high fructose diet in utero leads to gender-specific activation of molecular pathways responsible for insulin resistance, liver inflammation and liver steatosis in adults. High fructose enriched diets in pregnancy can have significant adverse long-term impact on health. Understanding the pathways involved can guide development of preventive and therapeutic approaches.
31026-3&id=fx1.jpg){kind=link}
31026-3&id=fx2.jpg){kind=link}