Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats.

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

Ethanol Consumption by Lactating Rats Induces Changes in Pup's Fatty Acid Profiles.

From parturition, lactating Wistar rats were given 20% ethanol in drinking water and solid diet ad libitum (ET group) or were pair-fed to the ET group (PF group) or were given water and solid diet ad libitum (control group, C). Animals were studied on day 12 of lactation and/or treatment, when dams were separated from their litters and 2-4 hours latter they were i.p. injected with oxytocin for milk collection under anaesthesia. Maternal food intake, weight gain and pup's body weight were lower in ET than in C rats. When compared to C rats, milk of ET dams had a decreased proportion of C14:0 and C22:6 n-3 fatty acids while an increase in C18:0,C16:1 and C18:1 n-9 was detected, whereas when compared to PF it had higher C8:0,C10:0,C18:0,C18:1 n-9, C18:2 n-6 and lower C20:5 n-3 and C22:6 n-3. Body weight was lower in pups from ET than in those from C or PF, and whereas brain weight and brain lipid content was lower in ET and PF pupsthan in C, total phospholipid (PL) brain content was similar among the groups. The ratio of C20:3 n-9 to C20:4 n-6 in brain PL was higher in ET pups than in either C or PF, indicating an essential fatty acid deficiency in the formers. Ethanol treatment also decreased the proportional amount of C18:2 n-6, C18:3 n-3, C20:4 n-6, C20:5 n-3 and C22:6 n-3 in brain PL as compared to C, whereas from these fatty acids only C18:3 n-3, C20:5 n-3 and C22:6 n-3 were decreased in PF. On the other hand, the proportion of C22:6 n-3 was significantly lower in the pups of ET group than in PF animals. Present results show that maternal intake of ethanol during lactation in the rat modifies milk lipid composition and that these effects are not caused by the undernutrition condition of the animals. These effects alter fatty acid composition of brain PL in pups, and such effect may contribute to its abnormal development.

Effects of ethanol intake on retinol concentration in the milk of lactating rats.

The effect of the consumption of ethanol (5%) on retinol concentration in milk was studied in the rat on day 12 after delivery, together with the evolution of dam body weight and pup growth rate. Female Wistar rats receiving alcohol (5%) in drinking water during lactation (N = 7) were compared to normal controls fed ad libitum (N = 6). The mean maternal alcohol intake was 3.96 +/- 0.23 g/kg body weight per day. To determine retinol levels in milk we used the Bessey and Lowry method, modified by Araújo and Flores ((1978) Clinical Chemistry, 24:386-392). The pups were separated from dams for a 2-4-h period, after which the dams were injected intraperitoneally with anesthetic and oxytocin. The concentration of retinol in milk was 162.88 +/- 10.60 micrograms/dl in the control group and 60.02 +/- 8.22 micrograms/dl in the ethanol group (P < 0.05). The ethanol group consumed less food than the controls and lost a significant amount of weight during lactation. On days 8, 10 and 12, the body weight of the pups from rats given ethanol (13.46 +/- 0.43, 16.12 +/- 0.48 and 18.60 +/- 0.91 g, respectively) were significantly lower (P < 0.05) than the weight of pups from controls (15.2 +/- 0.44, 18.36 +/- 0.54, 20.77 +/- 0.81 g). These data show that ethanol intake during the suckling period, even at low concentrations, decreases the amount of retinol in milk and, therefore, the amount available to the pups.

Effects of ethanol intake on retinol concentration in the milk of lactating rats

The effect of the consumption of ethanol (5 percent) on retinol concentration in milk studied in the rat on day 12 after delivery, together with the evolution of dam body weight and pup growth rate. Female Wistar rats receiving alcohol (5 percent) in drinking water during lactation (N=7) were compared to normal controles fed ad libitum (N=6). The mean maternal alcohol intake was 3.96 + 0.23 g/kg body weight per day. To determine retinol levels in milk we used the Bessey and Lowry method, modified by Araújo and Flores (1978) Clinical Chemistry, 24:386-392). The pups were separated from dams for a 2-4h period, after which the dams were injected intraperitoneally with anesthetic and oxytocin. The concentration of retinol in milk was 162.88 + 10.60 mug/dl in the control group and 60.02 + 8.22 mug/dl in the ethanol group (P<0.05). The ethanol group consumed less food than the controls and lost a significant amount of weight during lactation. On days 8, 10 and 12, the body weight of the pups from rats given ethanol (13.46 + 0.43, 16.12 + 0.48 and 18.60 + 0.91 g, respectively) were significantly lower (P<0.05) than the weight of pups from controls (15.2 + 0.44, 18.36 + 0.54, 20.77 + 0.81 g). These data show that ethanol intake during the suckling period, even at low concentrations, decreases the amount of retinol in milk and, therefore, the amount available to the pups.