<p>Beneficial Effect of Genistein on Diabetes-Induced Brain Damage in the ob/ob Mouse Model</p>

Abstract

Purpose: Diabetes mellitus (DM)-induced brain damage is characterized by cellular, molecular and functional changes. The mechanisms include oxidative stress, neuroinflammation, reduction of neurotrophic factors, insulin resistance, excessive amyloid beta (Aβ) deposition and Tau phosphorylation. Both antidiabetic and neuroprotective effects of the phytoestrogen genistein have been reported. However, the beneficial effect of genistein in brain of the ob/ob mouse model of severe obesity and diabetes remains to be determined. Methods: In this study, female ob/ob mice and lean control mice were fed with either a standard diet or a diet containing genistein (600mg/kg) for a period of 4 weeks. Body weight was monitored weekly. Blood was collected for the measurement of glucose, insulin and common cytokines. Mice brains were isolated for Western immunoblotting analyses. Results: Treatment with genistein reduced weight gain of ob/ob mice and decreased hyperglycemia compared to ob/ob mice fed the standard diet. The main findings show that genistein treatment increased insulin sensitivity and the expression levels of the neurotrophic factors nerve growth factor (NGF) and brain-derived neurotrophic factors (BDNF). In these mice, genistein also reduced Aβ deposition and the level of hyper-phosphorylated Tau protein. Conclusion: The results of our study indicate the beneficial effects of genistein in the obese diabetic mouse brain, including improving brain insulin signaling, increasing neurotrophic support, and alleviating Alzheimer's disease-related pathology.

Effects of Genistein and Exercise Training on Brain Damage Induced by a High-Fat High-Sucrose Diet in Female C57BL/6 Mice

“…Our results demonstrated that genistein or exercise treatment ameliorated the HFHS diet-induced increase in A β content. This effect of genistein on the A β level has been reported in the AD mouse model and the ob/ob mouse model [ 37 , 48 ]. However, to the best of our knowledge, this study was the first to show that genistein reduced the accumulation of A β using a western-style diet consisting of HFHS to induce obesity and T2DM.…”

“…Experimentally, genistein has been extensively studied in male and female mice as a promising therapy for the treatment of obesity and diabetes-induced cognitive dysfunction with similar efficacy because of its reported anti-inflammatory, anti-apoptotic, and antioxidant properties [ 32 ]. In addition, we have recently demonstrated a robust neuroprotective effect of genistein in a model of severe obesity [ 37 ]. In fact, four weeks of genistein treatment improved insulin signaling, increased expression of BDNF, and decreased the A β load and hyperphosphorylated tau in the brain of ob/ob mice [ 37 ].…”

“…In addition, we have recently demonstrated a robust neuroprotective effect of genistein in a model of severe obesity [ 37 ]. In fact, four weeks of genistein treatment improved insulin signaling, increased expression of BDNF, and decreased the A β load and hyperphosphorylated tau in the brain of ob/ob mice [ 37 ]. In the present study, the effects of exercise training and genistein supplementation on HFHS-induced brain injury were determined.…”

Early Postnatal Genistein Administration Affects Mice Metabolism and Reproduction in a Sexually Dimorphic Way

“…The hipoleptinemic action of GEN was documented in male adult rats, showing a reduction in leptin levels after only three days of treatment with a dose of 5 mg/kg body weight [ 69 ]. In female rats, GEN has no effects on the plasma levels of normal females, but it induces a reduction of serum leptin in pregnant females [ 70 ], as well as in obesity models [ 71 , 72 ].…”

The Beneficial Role of Natural Endocrine Disruptors: Phytoestrogens in Alzheimer’s Disease

“…In 2020, Li et al indicated that genistein has plenty of beneficial effects in diabetes mellitus-induced brain damage [ 66 ]. The authors revealed that this phytoestrogen not only improves brain insulin signaling but also increases neurotrophic support and alleviates AD-related pathologies, such as A β deposition and the level of hyperphosphorylated tau protein.…”