Methyl Donors Supplementation Attenuates the Adverse Effects of Maternal High Fructose Diet of Offspring Emotional and Cognitive Behaviors

Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.

Effect of Berberine on Expression of Hepatocyte Nuclear Factor-4α in Rats with Fructose-induced Insulin Resistance

The effects of berberine on the expression of hepatocyte nuclear factor-4α （HNF-4α） in liver of rats with fructose-induced insulin resistance and the molecular mechanism of berberine preventing insulin resistance were investigated. The experimental animals were divided into two groups of 16 animals each. The control group received a control routine diet containing 60% carbohydrate, and the study group a high-fructose diet containing 60% fructose as the sole source of carbohydrate. At the end of 6 weeks these were each subdivided into two groups. One was administered with berberine [187.5 mg/（kg·d） in 5 g/L carboxymethyl cellulose] by intragastric intubation and the other group was treated with a vehicle （5 g/L carboxymethyl cellulose）. The rats were fed on the same dietary regimen for the next 4 weeks. After the experimental period of 10 weeks, plasma glucose, insulin and triglyceride levels were measured. HOMA insulin resistance index （HOMA-IR） was assayed. Immunohistochemistry, semiquantitative RT-PCR and western blot were used to detect the expression of HNF-4α in liver. Compared with control diet, fructose feeding induced hyperinsulinemia, HOMA-IR and increased triglyceride （all P〈0.01）. Berberine prevented the rise in plasma insulin （P〈0.01）, HOMA-IR （P〈0.01） and triglyceride （P〈0.05） in the fructose-fed rats. No change in plasma glucose was seen among these groups. The mRNA and protein expression of HNF-4α was decreased in the fructose-fed rats, but berberine could promote its expression. It was concluded that berberine could prevent fructose-induced insulin resistance in rats possibly by promoting the expression HNF-4α in liver.

Glutathione depleting drugs, antioxidants and intestinal calcium absorption

Glutathione （GSH） is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2＋ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2＋ ab-sorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxida-tive/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca transport or the paracellular Ca route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2＋ pathway are decreased. The favonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2＋ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2＋ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2＋ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety,pharmacokinetics and pharmacodynamics of them.

Long-term high fructose and saturated fat diet affects plasma fatty acid profile in rats

As the consumption of fructose and saturated fatty acids(FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome,the aim of this study was to investigate the effects of a mod-erate(10 weeks) and a prolonged(30 weeks) high fructose and saturated fatty acid(HFS) diet on plasma FA com-position in rats.The effects of a few weeks of HFS diet had already been described,but in this paper we tried to es-tablish whether these effects persist or if they are modified after 10 or 30 weeks.We hypothesized that the plasma FA profile would be altered between 10 and 30 weeks of the HFS diet.Rats fed with either the HFS or a standard diet were tested after 10 weeks and again after 30 weeks.After 10 weeks of feeding,HFS-fed rats developed the metabolic syndrome,as manifested by an increase in fasting insulinemia,total cholesterol and triglyceride levels,as well as by impaired glucose tolerance.Furthermore,the plasma FA profile of the HFS group showed higher proportions of monounsaturated FAs like palmitoleic acid [16:1(n-7)] and oleic acid [18:1(n-9)],whereas the proportions of some polyunsaturated n-6 FAs,such as linoleic acid [18:2(n-6)] and arachidonic acid [20:4(n-6)],were lower than those in the control group.After 30 weeks of the HFS diet,we observed changes mainly in the levels of 16:1(n-7)(decreased) and 20:4(n-6)(increased).Together,our results suggest that an HFS diet could lead to an adaptive response of the plasma FA profile over time,in association with the development of the metabolic syndrome.