Dietary fat modulation of apoA-II metabolism and prevention of senile amyloidosis in the senescence- accelerated mouse

Abstract

Senescence-accelerated mouse-prone (SAMP1; SAMP1@Umz) is an animal model of senile amyloidosis with apolipoprotein A-II (apoA-II) amyloid fibril (AApoAII) deposits. This study was undertaken to investigate the effects of dietary fats on AApoAII deposits in SAMP1 mice when purified diets containing 4% fat as butter, safflower oil, or fish oil were fed to male mice for 26 weeks. The serum HDL cholesterol was significantly lower ( P Ͻ 0.01) in mice on the diet containing fish oil (7.4 ؎ 3.0 mg/dl) than in mice on the butter diet (38.7 ؎ 12.5 mg/dl), which in turn had significantly lower ( P Ͻ 0.01) HDL levels than mice on the safflower oil diet (51.9 ؎ 5.6 mg/dl). ApoA-II was also significantly lower ( P Ͻ 0.01) in mice on the fish oil diet (7.6 ؎ 2.7 mg/dl) than on the butter (26.9 ؎ 7.3 mg/dl) or safflower oil (21.6 ؎ 3.7 mg/dl) diets. The mice fed fish oil had a significantly greater ratio ( P Ͻ 0.01) of apoA-I to apoA-II, and a smaller HDL particle size than those fed butter and safflower oil. Severe AApoAII deposits in the spleen, heart, skin, liver, and stomach were shown in the fish oil group compared with those in the butter and safflower oil groups (fish oil Ͼ butter Ͼ safflower oil group, P Ͻ 0.05). These findings suggest that dietary fats differ in their effects on serum lipoprotein metabolism, and that dietary lipids may modulate amyloid deposition in SAMP1 mice.

Effect of Dietary Lipids on Longevity and Memory in the SAMP8 Mice

“…Previous studies have shown that a diet heavy in butter, saturated fatty acids, or fish oil with n -3 PUFAs, advances the severity of age-related senile amyloidosis, whereas soybeans enriched with n -6 PUFAs alleviate the severity of the age-related disease ( 19 ). These findings are contrary to the popular hypothesis that n -3 PUFAs are beneficial to health.…”

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

“…In our previous study, we reported that SAMP1 mice that were fed a fish oil diet had significantly lower apoA-II concentrations but more AApoAII deposits than those on a butter and safflower oil diet. 38 These results suggested altered metabolism or clearance of amyloid protein might be another factor controlling susceptibility towards amyloidosis. 39 ApoA-II is synthesized mainly in the liver in mice and secreted to the blood very quickly.…”

ApoA-I deficiency in mice is associated with redistribution of apoA-II and aggravated AApoAII amyloidosis

“…In this experiment, HDL appeared monotonic ( Fig. 2A ), and we marked size classes of HDL 1 , HDL 2 , and HDL 3 based on the distributions of apoA-I and apoA-II in WT mice and our previously reported results ( 14,29 ).…”

“…Electrophoresis was carried out at 25 mA for 2 h ( 14,29 ). The distribution of apoA-I, apoA-II, apoE, apoA-IV, and apoC-II protein among the HDL species was determined by Western blot analysis of 0.5, 2, 1, 1, and 2 l plasma, respectively, separated by nondenaturing PAGE.…”