A high-calorie diet (HCD) induces two mutually exacerbating effects contributing to diet-induced obesity (DIO): impaired glucose metabolism and increased food consumption. A link between the metabolic and behavioral manifestations is not well understood yet. We hypothesized that chronic inflammation induced by HCD plays a key role in linking together the two components of diet-induced pathology. Based on this hypothesis, we tested if a plasmid (DNA vaccine) encoding p62 (SQSTM1) would alleviate DIO including its metabolic and/or food consumption abnormalities. Previously we reported that injections of the p62 plasmid reduce chronic inflammation during ovariectomy-induced osteoporosis. Here we found that the p62 plasmid reduced levels of pro-inflammatory cytokines IL-1β, IL-12, and INFγ and increased levels of anti-inflammatory cytokines IL-4, IL-10 and TGFβ in HCD-fed animals. Due to this anti-inflammatory response, we further tested whether the plasmid can alleviate HCD-induced obesity and associated metabolic and feeding impairments. Indeed, p62 plasmid significantly reversed effects of HCD on the body mass index (BMI), levels of glucose, insulin and glycosylated hemoglobin (HbA1c). Furthermore, p62 plasmid partially restored levels of the satiety hormone, serotonin, and tryptophan, simultaneously reducing activity of monoamine oxidase (MAO) in the brain affected by the HCD. Finally, the plasmid partially reversed increased food consumption caused by HCD. Therefore, the administering of p62 plasmid alleviates both metabolic and behavioral components of HCD-induced obesity.
The social significance of diabetes mellitus lies in the fact that in addition to significant prevalence, this disease is associated with many complications. To facilitate the course of diabetes and its complications medicinal plants are widely used in traditional medicine. One of such plants is kidney bean (Phaseolus vulgaris). This plant is used in traditional medicine, especially for the secondary complications of diabetes. Since complications of diabetes are often associated with increased oxidative stress, the study of antioxidant properties of P. vulgaris is important to clarify the mechanism of its therapeutic effect. Present investigation shows that long-term oral administration of aqueous P. vulgaris pods extract in dose of 200mg/kg b.w. besides its pronounced hypoglycemic action also has a positive influence on the liver and kidney function markers in STZ-treated diabetic rats. The extract also inhibits free radical production and lipid peroxidation and activates antioxidant enzymes in liver and kidneys of rats with STZ-induced diabetes. Thus, our data reveal antioxidant properties of aqueous P. vulgaris pods extract that might have beneficial effect in treatment of diabetes.
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