Long-Term High-Fat Diet Consumption Depletes Glial Cells and Tyrosine Hydroxylase-Containing Neurons in the Brain of Middle-Aged Rats.

Mei-Chuan Chou,Yen-Chin Liu,Patrick Szu-Ying Yen,Ching-Kuan Liu,Hsiang-Chun Lee,Tzu-Han Hsieh,Shiou-Lan Chen,Chu-Huang Chen

doi:10.3390/cells11020295

Abstract

Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of neuronal degeneration. However, the effects of chronic dyslipidemia on brain function, especially in older individuals, remain unclear. In this study, middle-aged 37-week-old male Wistar-Kyoto rats were fed a normal diet (ND) or a 45% high-fat diet (HFD) for 30 weeks (i.e., until 67 weeks of age). To study the effects of chronic dyslipidemia on the brain, we analyzed spontaneous locomotor activity, cognitive function, and brain tissues in both groups of rats after 30 weeks. Compared with age-matched rats fed a ND, Wistar-Kyoto rats fed a HFD had dyslipidemia and showed decreased movement but normal recognition of a novel object. In our brain analyses, we observed a significant decrease in astrocytes and tyrosine hydroxylase–containing neurons in the substantia nigra and locus coeruleus of rats fed a HFD compared with rats fed a ND. However, hippocampal pyramidal neurons were not affected. Our findings indicate that the long-term consumption of a HFD may cause lipid metabolism overload in the brain and damage to glial cells. The decrease in astrocytes may lead to reduced protection of the brain and affect the survival of tyrosine hydroxylase–containing neurons but not pyramidal neurons of the hippocampus.

Highlights

Dopaminergic (DA) neurons are associated with the coordination of body movement
Compared with the normal diet (ND) group, rats in the high-fat diet (HFD) group showed a significant reduction in the number of tyrosine hydroxylase (TH)-containing neurons in the substantia nigra (SN) and locus coeruleus (LC), whereas the number of pyramidal neurons, which correlate with cognitive function and memory in the hippocampus, was similar between groups
We could not exclude the effects of obesity or organ damage induced by a long-term HFD on behavior, our results showed that long-term hyperlipidemia in middle-aged rats reduced locomotor activity and induced molecular changes in the rostral and caudal parts of the SN related to the progression of Parkinson’s disease (PD)

Summary

Introduction

The apoptosis of DA neurons in the substantia nigra (SN) induces motor deficiency and is believed to be a step in the progression of Parkinson’s disease (PD). Identifying the putative pathogenic factors and developing preventive strategies against DA neuron apoptosis has become of critical importance. Dyslipidemia may be a risk factor for neuronal degeneration. In patients with metabolic syndrome (MetS), dyslipidemia, such as hyperlipidemia or hypercholesterolemia, has been associated with an increased risk of diseases in the cardiovascular and nervous systems, such as atherosclerosis [3], heart disease [4], diabetes [5], and neurodegenerative disease [6,7]. Whether MetS or obesity is associated with degenerative neuronal disease is not clear. Several studies in animals have verified the effect of dyslipidemia on the progressive apoptosis of DA neurons, but all animal studies to date of DA neurons involving a high-fat diet (HFD) have been conducted in young adult rodents that do not represent middle-aged humans

Methods

Findings

Discussion

Conclusion