Sex-dependent susceptibility to brain metabolic dysfunction and memory impairment in response to pre- and postnatal high-fat diet.

The developing brain is sensitive to the impacts of early-life nutritional intake. This study investigates whether maternal high fat diet (HFD) causes glucose metabolism impairment, neuroinflammation, and memory impairment in immature and adult offspring, and whether it may be affected by postweaning diets in a sex-dependent manner in adult offspring. After weaning, female rats were fed HFD (55.9% fat) or normal chow diet (NCD; 10% fat) for 8 weeks before mating, during pregnancy, and lactation. On postnatal day 21 (PND21), the male and female offspring of both groups were split into two new groups, and NCD or HFD feeding was maintained until PND180. On PND21 and PND180, brain glucose metabolism-, inflammation-, and Alzheimer's pathology-related markers were by qPCR. In adult offspring, peripheral insulin resistance parameters, spatial memory performance, and brain glucose metabolism (18F-FDG-PET scan and protein levels of IDE and GLUT3) were assessed. Histological analysis was also performed on PND21 and adult offspring. On PND21, we found that maternal HFD affected transcript levels of glucose metabolism markers in both sexes. In adult offspring, more profoundly in males, postweaning HFD in combination with maternal HFD induced peripheral and brain metabolic disturbances, impaired memory performance and elevated inflammation, dementia risk markers, and neuronal loss. Our results suggest that maternal HFD affects brain glucose metabolism in the early ages of both sexes. Postweaning HFD sex-dependently causes brain metabolic dysfunction and memory impairment in later-life offspring; effects that can be worsened in combination with maternal HFD.

Sex-specific effects of high-fat diet on rat brain glucose metabolism and early-onset dementia symptoms.

Peripheral metabolic disturbances are associated with a variety of clinical health consequences and may contribute to the development of neurocognitive disorders. This study investigates whether long-term high-fat diet (HFD) consumption changes the brain glucose metabolism and impairs memory performance in a sex-dependent manner. Male and female rats, after weaning, were fed HFD or normal chow diet (NCD) for 16 weeks. Behavioral tests for spatial memory and an 18 F-FDG-PET scan were performed. Also, the expression of brain insulin resistance markers and Alzheimer's pathology-related genes was assessed by qPCR. The Morris water maze and Y-maze results showed, respectively, that memory retrieval and spatial working memory were impaired only in HFD male rats compared to NCD controls. In addition, measuring whole brain 18 F-FDG uptake indicated a significant reduction in glucose metabolism in male but not female HFD rats. Analysis of 15 genes related to glucose metabolism and Alzheimer's pathology, in the hippocampus, showed that expression of GLUT3, IRS2, and IDE is significantly reduced in HFD male rats. Our results suggest that sex affects the HFD-induced dysregulation of brain glucose metabolism and cognitive performance.

Effect of Different Times of Intraperitoneal Injections of Human Bone Marrow Mesenchymal Stem Cell Conditioned Medium on Gentamicin-Induced Acute Kidney Injury.

PURPOSE: This study examined the effect of mesenchymal stem cells' conditioned media on the severity of acute kidney injury. MATERIALS AND METHODS: Acute kidney injury was induced in male rats with 100 mg/kg of gentamicin for six consecutive days intraperitoneally. After inducing the standard model of acute kidney injury, the conditioned medium of 5 × 106 cells was calculated for each kilogram of body weight of the rats. Then, it was injected in three different injection patterns other than the baseline injection of gentamicin. The rats were randomly divided into four groups: control group (n = 18) that did not receive any treatment, gentamicin group (n = 18) that received gentamicin at a dosage of 100 mg/kg for six consecutive days intraperitoneally, sham group (n = 54) that received gentamicin for six consecutive days, and an experimental group (n = 54) that received gentamicin for six consecutive days. Serum biochemical analysis and histological changes were studied and analyzed in all groups. RESULTS: Although human mesenchymal stem cells' conditioned media did not improve serum and tissue markers in the treatment groups, a relative improvement was observed in some indicators of tissue damage. CONCLUSION: Secretory factors of human mesenchymal stem cells can be partly protective against gentamicin-induced nephrotoxicity. .