Previous studies have shown that canola oil (CA), compared with soybean oil (SO), shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats, a widely used model for hemorrhagic stroke. SHRSP rats are highly sensitive to dietary cholesterol manipulations because a deficiency of membrane cholesterol makes their cell membranes weak and fragile. Phytosterols, abundant in CA but not in SO, can inhibit the absorption of cholesterol and also replace a part of cholesterol in cell membranes. This study was performed to determine whether the high concentration of phytosterols in CA might account for its life-shortening effect on SHRSP rats. Male, 35-d-old SHRSP rats (n = 28/group) were fed semipurified diets containing CA, SO, CA fortified with phytosterols (canola oil + phytosterols, CA + P), SO fortified with phytosterols (soybean oil + phytosterols, SO + P), corn oil (CO), olive oil (OO) or a fat blend that mimicked the fat composition of a representative Canadian diet (Canadian fat mimic, CFM; 10 g/100 g diet). These fats provided 97, 36, 207, 201, 114, 27 and 27 mg phytosterols/100 g diet, respectively. Ten rats from each group were killed after 30-32 d for blood and tissue analyses. The remaining rats (18/group) were used for determination of life span. The life span of SHRSP rats fed the high phytosterol oils (CA, CA + P, SO + P and CO) was significantly (P<0.05) shorter than that of CFM- and SO-fed rats. At 30-32 d, the groups fed the high phytosterol oils had greater levels of phytosterols and significantly (P<0.05) higher ratios of phytosterols/cholesterol in plasma, RBC, liver and kidney, and a significantly (P<0.05) lower RBC membrane deformabilty index than the groups fed oils low in phytosterols (SO, OO and CFM). The mean survival times were correlated with RBC deformability index (r(2) = 0.91, P = 0.0033) and cholesterol concentration (r(2) = 0.94, P = 0.0016), and inversely correlated with RBC phytosterol concentration (r(2) = 0.58, P = 0.0798) and phytosterols/cholesterol (r(2) = 0.65, P = 0.0579), except in the OO group. This study suggests that the high concentration of phytosterols in CA and the addition of phytosterols to other fats make the cell membrane more rigid, which might be a factor contributing to the shortened life span of SHRSP rats.

In a 16-wk study, weanling Wistar rats (32 males and 32 females) were fed a modified AIN-76 diet containing 20% fat with various (n-3) fatty acids. All dietary fats provided the same amount of saturates, monounsaturates, and total essential fatty acids [(n-6) + (n-3)]. The control diet contained lard/corn oil (L/CO). The other diets contained (n-3) fatty acids from linseed oil (LSO), from linseed oil + menhaden oil (LSO + MO) or from menhaden oil (MO). The (n-3) diets reduced total and HDL-cholesterol, particularly in rats fed the MO diet. Platelet thromboxane levels were equally depressed by the LSO and MO diets. Dietary (n-3) fatty acids significantly elevated docosahexaenoic acid in livers and hearts of male and female rats, with females reaching higher levels. This increase was accompanied by reduced arachidonic acid, except for hearts of females in which the major decrease was in linoleic acid. Overall, enzyme activities in the MO-fed group were decreased to the following levels (relative to the activity in the control group): heart Mn superoxide dismutase (SOD), 28%; liver CuZnSOD, 82%; aorta CuZnSOD, 32%. Greater reductions in these enzyme activities were seen in the female rats fed the MO diet compared with male rats. Lipid peroxidation, assessed by urinary, heart and liver thiobarbituric acid reactants, was increased by dietary (n-3) fatty acids (MO greater than LSO + MO greater than LSO greater than L/CO) and was higher in females than in males. These results indicate that enhanced lipid peroxidation occurs with the increased oxidative stress of elevated tissue (n-3) fatty acids accompanied by reduced SOD activity.

Perfluorooctanesulfonate (PFOS) is one of a class of industrial chemicals known as perfluoroalkyl acids, which have a wide variety of uses as surfactants and stain repellants. The presence of fluorochemical residues in human blood, plasma, or serum from sample populations worldwide is indicative of widespread human exposure. Previous studies demonstrated that PFOS alters fatty acid metabolism in the liver of rodents and that this leads to peroxisome proliferation. This study was undertaken to (1) confirm the effects of PFOS on rat liver, (2) identify additional target organs and systems, and (3) further explore the biochemical and molecular changes associated with PFOS exposure. The results confirmed that liver was a primary target for PFOS. Hepatomegaly, decreased serum triglycerides and cholesterol, and increased expression of the genes for acyl-coenzymeA oxidase 1 (ACOX1) and cytochrome P-450 4A22 (CYP4A22) were indicative of exposure to a peroxisome proliferator. Changes in liver fatty acid profiles included increased total monounsaturated fatty acid levels and decreased total polyunsaturated fatty acids, as well as an increase in linoleic acid levels and a decrease in longer chain fatty acids. These changes were similar to those induced by relatively weak peroxisome proliferators. Disruptions in hepatic fatty acid metabolism may contribute to changes in red blood cell membranes, resulting in increased lysis and cell fragility. Serum thyroid hormone levels were decreased in PFOS-treated rats, while the kidney and cardiovascular systems were not significant targets. Residue analyses indicated that PFOS accumulation in tissues was dose dependent, appearing preferentially in the liver at lower doses but increasing in serum and other organs relative to liver at higher doses.

There is increased acceptance of fortifying habitual foods with plant sterols and their saturated derivatives, stanols, at levels that are considered safe. These sterols and stanols are recognized as potentially effective dietary components for lowering plasma total and LDL cholesterol. Our previous studies have shown that daily consumption of plant sterols promotes strokes and shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats. These studies question the safety of plant sterol additives. The present study was performed to determine whether a large intake of plant stanols would cause nutritional effects similar to those seen with plant sterols in SHRSP rats. Young SHRSP rats (aged 26-29 d) were fed semipurified diets containing commercial margarines fortified with either plant stanols (1.1 g/100 g diet) or plant sterols (1.4 g/100 g diet). A reference group of SHRSP rats was fed a soybean oil diet (0.02 g plant sterols/100 g diet and no plant stanols). Compared to soybean oil, both plant stanol and plant sterol margarines significantly (P < 0.05) reduced the life span of SHRSP rats. At the initial stages of feeding, there was no difference in the survival rates between the two margarine groups, but after approximately 50 d of feeding, the plant stanol group had a slightly, but significantly (P < 0.05), lower survival rate. Blood and tissue (plasma, red blood cells, liver, and kidney) concentrations of plant sterols in the plant sterol margarine group were three to four times higher than the corresponding tissue concentrations of plant stanols in the plant stanol group. The deformability of red blood cells and the platelet count of SHRSP rats fed the plant sterol margarine were significantly (P < 0.05) lower than those of the plant stanol margarine and soybean oil groups at the end of the study. These parameters did not differ between the soybean oil and plant stanol margarine groups. These results suggest that, at the levels tested in the present study, plant stanols provoke hemorrhagic stroke in SHRSP rats to a slightly greater extent than plant sterols. The results also suggest that the mechanism by which plant stanols shorten the life span of SHRSP rats might differ from that of plant sterols.

SUMMARYWhen compared with laboratory chow, a defined, semipurified diet prevented diabetes, reduced the frequency of insulitis, increased thymus weight and total white blood cell count, and doubled thymus T-helper/T-suppressor cell ratios in diabetes-prone BB rats. These data show that the diabetic syndrome in BB rats may be prevented or delayed by changes in diet, which may occur through alteration of pathogenic defects in the immune system. DIABETES 1985; 34:1059-62.T he fact that only up to 50% of unaffected twins of individuals with type I, insulin-dependent diabetes mellitus (IDDM) become diabetic underscores the major role of environmental factors in the expression of this genetically transmitted disease. With the exception of tropical malnutrition diabetes, a unique ketosis-resistant form of IDDM in which there is an acknowledged involvement of diet, 1 there are no data directly linking diet to incidence of type I IDDM in humans. 2 The two main obstacles have been the inability to identify prospective diabetic humans and the inherent difficulties in obtaining accurate and representative dietary information.The recent availability of the spontaneously diabetic BB rat has provided a unique model that has many of the features of human type I diabetes, permitting long-term prospective studies to be carried out. 34 BB rat diabetes appears to be an autoimmune disease resulting from the destruction of the insulin-producing beta cells of the pancreas by the animal's own immune system. Development of overt diabetes may require inheritance of at least three characteristics: mononuclear cell infiltration of the pancreas (insulitis), the pres- ence of the major histocompatibility complex haplotype (RT1 U ), and lymphopenia. 56 The protective effect of neonatal thymectomy, 78 decreased thymus (T)-derived lymphocytes in blood and lymphoid organs, 9 reduced T-helper (T h )/T-suppressor (T s ) cell ratios, 6 and decreased thymus weight in diabetes-prone BB rats all point to a key role for the thymus in the pathogenesis of this syndrome.Diet can have dramatic effects on the immune system, particularly the thymus, which seems uniquely sensitive to manipulation of nutritional variables. 10 Furthermore, it has recently been hypothesized that environment (diet) could be an important factor influencing development of diabetes in BB rats. 811 In previous studies we observed differences in incidence and age at onset, which suggested that, compared with a chow diet, a defined, semipurified AIN-76 diet 12 might modify development of the syndrome. 8 Any approach to this question must consider at least three points: (1) effect of diet on insulitis, diabetes incidence, age at onset; (2) net diet/ immune system interactions (i.e., varying susceptibility of specific T-cell subsets); and (3) presence or absence of diabetogens in the diet. MATERIALS AND METHODSExperiment 1. This experiment was designed to examine directly the effects of ad libitum feeding of a ground laboratory rat chow diet (N = 40) or a defined, semipurified AIN-76 ...