Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer’s disease-induced estrogen deficient rats

Abstract

Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused with β-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared to the Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly, cortisol levels were increased by Alzheimer's disease but decreased by intermittent fasting. Intermittent fasting improved dyslipidemia and liver damage index compared to ad libitum. Alzheimer's disease lowered low-density lipoprotein cholesterol and serum triglyceride levels compared to Non-Alzheimer's disease. In conclusion, Alzheimer's disease impaired not only cognitive function but also disturbed energy, glucose, lipid, and bone metabolism in ovariectomized rats. Intermittent fasting protected against the deterioration of these metabolic parameters, but it exacerbated bone mineral density loss and insulin resistance at fasting in Alzheimer's disease-induced estrogen-deficient rats. Impact statement Intermittent fasting was evaluated for its effects on cognitive function and metabolic disturbances in a rat model of menopause and Alzheimer's disease. Intermittent fasting decreased skin temperature and fat mass, and improved glucose tolerance with decreasing food intake. Intermittent fasting also prevented memory loss: short-term and special memory loss. ...

Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer’s Disease: A Scoping Review

“…All of these mice were designed to increase the deposition rate of β-amyloid in the brain with some as early as two months old [ 38 ]. Interestingly, only one study was found to employ ovariectomized female rats instead, and they were infused with β-amyloid peptides into their hippocampus [ 40 ]. The age of the mice and rats at the start of the intervention varied from study to study.…”

“…The age of the mice and rats at the start of the intervention varied from study to study. Three studies started the intervention as early as two to three months old [ 38 , 40 , 42 ], while the other at five months old [ 41 ], and lastly at 12 months old [ 39 ].…”

“…Three studies underwent the ADF method where food was deprived for a period of 24 h [ 38 , 41 , 42 ], while the remaining two studies employed a TRF protocol of 3 h per day [ 40 ] and 2 days per week of food deprivation [ 39 ]. The intervention duration was also found to be wide-ranging across studies.…”

“…For the ADF protocol, the shortest duration was 4 months [ 38 ], followed by 5 months [ 41 ], and the longest at 14 months [ 42 ]. The time-restricted protocol of 3 h per day started at the beginning of the dark cycle (7 to 10 PM), which corresponds to the morning for humans for a period of 2 months [ 40 ], while the 2 days per week food restriction was conducted for 9 months [ 39 ].…”

“…The majority of the studies reported in this review utilized immunohistochemical (IHC) analyses for the detection of β-amyloid plaque formation [ 38 , 39 , 40 , 41 ]. However, they differed in terms of the staining or primary antibodies used to detect β-amyloid.…”