Galactose metabolism and ovarian toxicity

Liu, Gentao; Hale, Georgina E.; Hughes, Claude L.

doi:10.1016/s0890-6238(00)00096-4

Cited by 88 publications

(57 citation statements)

References 74 publications

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“…This conversion of galactose to glucose can be enhanced by glucose via an increase in the activity of galactose-1-phosphate uridyltransferase (GALT) in the liver and also via the action of insulin 17) . If there is a block in either step, galactosemia occurs, which can cause disorders such as ovarian dysfunction or cirrhosis 18) . If galactose is present as a monosaccharide in VLDL and the liver, galactose should be converted to glucose by GALT.…”

Section: Discussionmentioning

confidence: 99%

Kefiran Reduces Atherosclerosis in Rabbits Fed a High Cholesterol Diet

Uchida

Ishii

Inoue

et al. 2010

JAT

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Aim:Kefiran is an exopolysaccharide produced by Lactobacillus kefiranofaciens, and has been proposed to have many health-promoting properties. We investigated the antiatherogenic effect of kefiran on rabbits fed a high-cholesterol diet. Methods: Male New Zealand White rabbits were fed a 0.5% cholesterol diet without (control group, n 7) or with kefiran (kefiran group, n 8) for eight weeks. The aorta was analyzed by histochemistry and atherosclerotic lesions were quantified. Lipids and sugars in serum were measured. Foam cell formation of RAW264.7 by VLDL derived from both groups of rabbits was also investigated. Results: Cholesterol, triglyceride and phospholipids levels of serum and lipoprotein fractions were not significantly different between these groups. Atherosclerotic lesions of the aorta in the kefiran group were statistically lower than those of the control group, with marked differences in the abdominal aorta. T-lymphocytes were not detectable in the aorta of the kefiran group. Cholesterol contents in stools were almost identical in both groups. Cholesterol content in the liver of the kefiran group was statistically lower than in the control group. Galactose content of VLDL derived from the kefiran group was higher, and the lipid peroxidation level was much lower than in the control group. RAW264.7 macrophages treated with VLDL from the kefiran group showed a more spherical shape and accumulated statistically lower cholesterol than macrophages treated with VLDL from the control group. Conclusion: Orally derived kefiran is absorbed in the blood. Kefiran prevents the onset and development of atherosclerosis in hypercholesterolemic rabbits by anti-inflammatory and anti-oxidant actions. J Atheroscler Thromb, 2010; 17:980-988.

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Section: Discussionmentioning

confidence: 99%

Kefiran Reduces Atherosclerosis in Rabbits Fed a High Cholesterol Diet

Uchida

Ishii

Inoue

et al. 2010

JAT

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“…This suggests that galactose does not enter glycolysis in granulosa cells, despite the theoretical availability of this pathway. The ovary in rodents and humans has an abundance of the enzymes required to metabolise galactose utilising the Leloir pathway (Liu et al 2000), but little is known of the patterns of expression of these enzymes in ruminants. The accumulation of galactose or its metabolites is associated with impaired ovarian function in the human, which arises typically because of a deficiency or a mutation of galactose-1-phosphate uridyltransferase, one of the key enzymes required for the metabolism of galactose.…”

Section: Discussionmentioning

confidence: 99%

The effect of monosaccharide sugars and pyruvate on the differentiation and metabolism of sheep granulosa cells in vitro

Campbell¹,

Onions²,

Kendall³

et al. 2010

Reproduction

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The objective of this study was to investigate the effect of three monosaccharides or pyruvate on the ability of gonadotrophins to induce cellular proliferation and differentiation of cultured sheep granulosa cells. Lactate production and levels of mRNA expression for the glucose transporters SLC2A1, SLC2A4, SLC2A5 and SLC2A8 were also determined. No energy source in the culture media reduced cell number (50%) and oestradiol (E 2 ) production. Dose and type of monosaccharide had a highly significant (P!0.001) effect on FSHinduced differentiation of the granulosa cells, and there was a highly significant interaction (P!0.001). Glucose supported higher levels of E 2 production than fructose, which was in turn higher than galactose (P!0.001). In contrast, pyruvate at low doses supported similar levels of E 2 production as glucose, but higher doses were markedly inhibitory to E 2 production (P!0.001). Cells responded positively to insulin (P!0.001) in the presence of all three monosaccharides. Glucose and the high doses of fructose resulted in the accumulation of lactate (P!0.001), but pyruvate, galactose and the low dose of fructose resulted in low lactate production. SLC2A5 expression was not detected and SLC2A8 expression was not affected, but SLC2A1 and SLC2A4 expression was depressed (P!0.05) by culture in the presence of fructose and glucose. These data show that glucose, metabolised under anoxic conditions to lactate, is the preferred energy substrate to support the gonadotrophin-induced differentiation of ovine granulosa cells in vitro, and that fructose and pyruvate, but not galactose, are alternative energy substrates despite marked differences in the way these substrates are metabolised.

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“…In ruminants, fructose is thought to be rapidly metabolised to glucose in the liver (Luick et al 1957), which may then trigger insulin release, but in primates and humans, fructose has been reported to have little effect on insulin and leptin release or on the concentrations of blood glucose (Curry 1989, Havel 1997, Teff et al 2004. In contrast, enzymes involved in the metabolism of galactose are abundantly and actively expressed in the ovary (Heidenreich et al 1993) and in humans ovarian dysfunction is observed in individuals with deficiencies or mutations in these enzymes (Liu et al 2000). In ruminants, however, the supplementation of diets high in galactose, such as those containing lupin grain (van Barneveld 1999), stimulates folliculogenesis and increases fecundity in ewes (Knight et al 1975) although evidence of the effects of this intervention on insulin concentrations is equivocal (Munoz-Gutierrez et al 2002, Somchit et al 2007.…”

Section: Introductionmentioning

confidence: 99%

The effect of systemic and ovarian infusion of glucose, galactose and fructose on ovarian function in sheep

Campbell¹,

Kendall²,

Onions³

et al. 2010

Reproduction

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Glucose is a critical metabolic fuel in most mammals although many foodstuffs also contain high levels of the monosaccharides, galactose and fructose. The aims of this work were to determine the insulin response to challenges of these sugars (experiment 1) and to examine the effect of systemic (experiment 2) and direct ovarian (experiment 3) infusion of these monosaccharides on ovarian function in ewes with autotransplanted ovaries. In experiment 1, both fructose (fourfold increase peaking in 2 h) and galactose (twofold increase; 30 min) elicited markedly different (P!0.001) insulin responses than glucose (sevenfold increase; 20 min) although the total amount released following fructose and glucose challenge was similar. In experiment 2, low-dose systemic fructose infusion had no acute effect on insulin but did depress FSH (P!0.05), and following the end of fructose infusion, a transient increase in FSH and insulin was observed (P!0.05), which was associated with an increase (P!0.05) in ovarian oestradiol and androstenedione secretion. Systemic infusion of neither glucose nor galactose had a significant effect on ovarian steroidogenesis although glucose acutely suppressed insulin levels. In contrast, ovarian arterial infusion of fructose and glucose had no effect on ovarian function whereas galactose suppressed ovarian follicle number and steroid secretion (P!0.05). In conclusion, this work indicates that fructose and galactose can influence ovarian function in vivo in sheep and that different mechanisms are involved. Thus, fructose exerts stimulatory effects through indirect modulation of peripheral insulin and/or gonadotrophin levels whereas galactose exerts primarily suppressive effects by direct actions on the ovary.

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Galactose metabolism and ovarian toxicity

Cited by 88 publications

References 74 publications

Kefiran Reduces Atherosclerosis in Rabbits Fed a High Cholesterol Diet

Kefiran Reduces Atherosclerosis in Rabbits Fed a High Cholesterol Diet

The effect of monosaccharide sugars and pyruvate on the differentiation and metabolism of sheep granulosa cells in vitro

The effect of systemic and ovarian infusion of glucose, galactose and fructose on ovarian function in sheep

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