High‐fat diet reduced dendritic spine density, but it did not affect cognitive function in spontaneous diabetic torii rats

Abstract

Diabetes is a known risk factor for dementia, several factors are involved in the pathogenesis of diabetes including genetic predisposition, and high calorie diet consumption. We previously reported that long-term high-fat diet (HFD) consumption led to prediabetes, which associated with cognitive impairments. However, the effects of long-term HFD consumption on metabolic and brain function in genetically type 2 diabetes (T2DM) model have not been investigated. Therefore, we hypothesized that long-term HFD consumption aggravates metabolic and cognitive impairments in T2DM rats. Sixteen Spontaneous Diabetic Torii (SDT) rats, which is a genetically engineered T2DM rats, and eight wild type (WT) rats were used. At the age of 8 weeks old, SDT rats were divided into two dietary groups either normal diet or HFD feeding for 12 weeks. WT rats were received a normal diet entire the study. At 20 weeks old, metabolic parameters, the hippocampal dependent cognitive function using novel object location (NOL) test, and hippocampal dendritic spine density were determined. Our data demonstrated that, at 20 weeks old, SDT rats in both dietary groups exhibited their diabetic characters as indicated by hyperglycemia, hypoinsulinemia, and insulin insensitivity. HFD feeding did not aggravate diabetic status, but it significantly induced body weight gain, visceral fat deposition, hypertriglyceridemia, and hypercholesterolemia (as shown in Figure 1). Unexpectedly, hippocampal dependent cognitive impairments were not observed in both normal diet and HFD-fed SDT rats, when compared with WT rats (Figure 1). However, brain mitochondrial dysfunction and dendritic spine loss were observed in both dietary groups of SDT rats. Interestingly, the reduction of dendritic spine density was greater in HFD-fed SDT rats than normal diet-fed SDT rats (Figure 1). Long-term HFD consumption induced truncal obesity, dyslipidemia, and reduced dendritic spine density in SDT rats, but it did not affect hippocampal dependent cognitive function. It is possible that the duration of HFD feeding was insufficient to promote cognitive impairments in genetically T2DM rats.