Methods and related compositions for treating or preventing obesity, insulin resistance disorders, and mitochondrial-associated disorders
A technology for obesity and compounds, applied in the direction of drug combinations, active ingredients of hydroxyl compounds, anti-toxic agents, etc., can solve problems such as limited effects
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Embodiment 1
[1638] Example 1: Metabolic activity of sirtuin activators in a diet-induced obesity (DIO) mouse model
[1639] To determine whether SIRT-1 activators prevent obesity and the associated development of insulin resistance, male C57BL6J mice chronically placed on a high-fat diet for 16 weeks were given resveratrol (by food admixture). Extensive phenotypic and molecular analyzes of mice were performed to identify regulatory pathways affected by Sirt-1 activation. See, for example Figure 17-21 The results shown.
[1640] The results showed that the mice had good tolerance to resveratrol as a food additive and did not cause anorexia. In this long-term study, 50 male C57BL6J mice (age 5 weeks) were analyzed for 18 weeks. 10 animals as a group, divided into the following 5 groups:
[1641] 1: normal diet
[1642] 2: Normal diet + resveratrol (200mg / kg / day)
[1643] 3: High-fat diet
[1644] 4: High fat diet + resveratrol (200mg / kg / day)
[1645] 5: High-fat diet + resveratrol ...
Embodiment 2
[1683] Example 2: Metabolic activity of sirtuin activators in the Zucker diabetic rat model
[1684] Oral administration of resveratrol (200mg / kg), metformin (200mg / kg), or a combination of the two to Zucker fatty diabetic rats (ZOF / Gmicrl-fa / fa) twice a day (total dose 400mg / kg / day) (200mg / kg each) or vehicle (2% Tween 80, 10ml / kg) for up to 42 days. Eight rats (six weeks old, 190+10 g) were used in each group. Animals were fasted for 24 h before oral glucose tolerance test (glucose dose 2 g / kg, PO) on day 43. Blood samples were collected from the retro-orbital sinus 35 minutes before the glucose load (fasting blood glucose) and 90 minutes after the oral glucose load. Serum glucose levels were determined by a Hitachi Model 750 automatic analyzer. For the results of this experiment, see Figure 23 . Also after 43 days daily body weight and food intake showed no statistical difference among the 4 groups. Also, there was no difference between the four groups in fasting blo...
Embodiment 3
[1685] Example 3: Biochemical and histological analysis of the diet-induced obesity (DIO) mouse model
[1686] Diet-induced obesity was induced in mice as described in Example 1 above. Biochemical and histological analyzes were performed on mice fed a control diet (C), a high fat diet (HF) or a high fat diet plus 400 mg / kg / day resveratrol (HF+R400) (see Example 1).
[1687] Figure 24 Shown are the results of body weight change experiments, food intake experiments and body fat content experiments conducted as described in Example 1 above. Pups were fed a control diet (C), a control diet plus 400 mg / kg / day resveratrol (C+R400), a high-fat diet (HF), or a high-fat diet plus 400 mg / kg / day resveratrol (HF+R400). Rats were 9 weeks old. The upper left shows a graph of the body weight change of mice in the four diet groups over a 9-week period. The upper right shows a graph of mouse food intake expressed in kcal / 24 hr for the four diet groups. A comparison of the body fat conten...
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