To identify the causative substances for the shortening of survival time by rapeseed (Canola) oil in stroke-prone spontaneously hypertensive rats (SHRSP), SHRSP were fed on a standard chow supplemented with 10 w/w% soybean oil (control), rapeseed oil, one of the fractions of rapeseed oil obtained by super critical gas extraction (SCE) under a pressure of 180-bar or 350-bar, at 40 degrees C, or the residue from the extraction (with 0.5% NaCl in drinking water). In another series of experiment, SHRSP were fed for 8 weeks on the above-mentioned diets without salt loading and autopsied. Fatty acid compositions in these diets were similar, except in the soybean oil diet, and phytosterol contents were: (diet containing) 180-bar fraction>residue>rapeseed oil>350-bar fraction>soybean oil. Survival times in the rapeseed oil, 350-bar fraction and residue groups were shorter than, whereas that in the 180-bar fraction was similar to in the soybean oil group. In the 8-week feeding experiment, chronic nephropathy was found frequently in the groups other than the soybean oil group. The heart weights were higher in the rapeseed oil and residue groups. Cerebral necrosis was found in the residue group. Taken together, the followings are concluded, (1) Neither the fatty acid composition, nor the amount of phytosterols in the diets appeared to be decisive in the shortening of life. (2) SCE appeared to produce a safe (180-bar) fraction, though it failed to separate clearly the causative substances into specific fractions. (3) The factors that facilitate the genetic disease of SHRSP appear to exist in rapeseed oil. However, they might not be identical to those responsible for the life-shortening, since there were no findings common across the rapeseed oil, 350-bar and residue groups, which showed similar life-shortening.

Algorithms↗

PubMed2005

Changes in dietary fatty acids and life style as major factors for rapidly increasing inflammatory diseases and elderly-onset diseases.

Explore the source record for details and available documents.

Aging↗

PubMed2005

[Need to change the direction of cholesterol-related medication--a problem of great urgency].

The cholesterol hypothesis implies that reducing the intake of saturated fatty acids and cholesterol and increasing that of polyunsaturated fatty acid are effective in lowering serum total cholesterol (TC), and thereby reducing the incidence of coronary heart disease (CHD). However, these dietary recommendations are essentially ineffective in reducing TC in the long run, but rather increase mortality rates from CHD and all causes. The reported "apparent relative risk of high TC in CHD mortality" (the ratio of mortality at the highest/lowest TC levels) varied several-fold among populations studied. The incidence of familial hypercholesterolemia (FH) in a population was proposed to be a critical factor in the observed variability, which could be accounted for by assuming that 1) the high CHD mortality rate in high-TC groups is mainly a reflection of the incidence and severity of FH, and 2) high TC is not a causative factor of CHD in non-FH cases. This interpretation is supported by recent observations that high TC is not positively associated with high CHD mortality rates among general populations more than 40-50 years of age. More importantly, higher TC values are associated with lower cancer and all-cause mortality rates among these populations, in which relative proportions of FH are likely to be low (circa 0.2%). Although the effectiveness of statins in preventing CHD has been accepted in Western countries, little benefit seems to result from efforts to limit dietary cholesterol intake or to TC values to less than approximately 260 mg/dl among the general population and the elderly. Instead, an unbalanced intake of omega6 over omega3 polyunsaturated fats favors the production of eicosanoids, the actions of which lead to the production of inflammatory and thrombotic lipid mediators and altered cellular signaling and gene expression, which are major risk factors for CHD, cancers, and shorter longevity. Based on the data reviewed here, it is urgent to change the direction of current cholesterol-related medication for the prevention of CHD, cancer, and all-cause mortality.

Anticholesteremic Agents↗

PubMed2004

HIV-1 nef suppression by virally encoded microRNA.

BACKGROUND: MicroRNAs (miRNAs) are 21 to approximately 25-nucleotides (nt) long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi), depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs) inhibited the transcription of HIV-1. RESULTS: Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA) that corresponded to a predicted nef miRNA (approximately 25 nt, miR-N367) can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2). In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. CONCLUSIONS: These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.

Acquired Immunodeficiency Syndrome↗

PubMed2004

HIV-1 Nef protein in the nucleus influences adipogenesis as well as viral transcription through the peroxisome proliferator-activated receptors.

BACKGROUND: Although the HIV-1 Nef protein (27 kDa) localizes primarily in cytoplasm, there is considerable evidence suggesting its occasional localization in the nucleus. Nef is known to play an important role in transcriptional events and viral replication, but the actual target of Nef in the nucleus remains to be identified. OBJECTIVE: To examine the functional roles of Nef in the nucleus and its possible interactions with other unknown factors in the nucleus. METHODS: High-density microarray analysis was used to screen directly the unique functions of Nef on host gene transcription. The nuclear localization of Nef and its effects on the expression of peroxisome proliferator-activated receptors (PPAR) was examined using PPAR promoter/reporter assay and immunoblotting. A long terminal repeat/reporter assay was used to investigated the effects of Nef and PPAR on viral transcription. RESULTS: Nef in the nucleus suppressed PPAR gamma expression and reduced fatty acid levels in human T and macrophage cell lines. Expression of Nef or PPAR suppressed viral replication; the effect of PPAR gamma or retinoid X receptor-alpha on viral replication were reduced by coexpression of Nef in MT(-)4 T cells. CONCLUSION: Nef may be involved in both viral replication and the wasting syndrome associated with AIDS.

Adipose Tissue↗

PubMed2004

Factors other than phytosterols in some vegetable oils affect the survival of SHRSP rats.

Unusual survival-shortening activities of some vegetable oils were detected in stroke-prone spontaneously hypertensive (SHRSP) rats, and phytosterol (PS) in the oils and the tissue tocopherol status have been suggested to be the factors for the activities. Here, we re-evaluated the contribution of PS to the survival-shortening, and examined the hepatic tocopherol status. A basal diet for rodents and a test oil were mixed at a 9:1 ratio, and the diet was given to male SHRSP rats upon weaning. The total and major PS contents of the diets and tissue lipids did not correlate with relative survival time. The free fatty acid fractions obtained by lipase and alkaline hydrolyses of canola oil (Can) and the original Can contained PS in comparable amounts but the free fatty acid fractions did not exhibit survival-shortening activities compared with the soybean oil (Soy) group. The activity was not detected in the ethyl acetate extracts of the aqueous phase after the hydrolysis. When a commercially available PS preparation was added to the Soy diet at an amount 2.8-fold higher than that in the Can diet, the mean survival time was shortened but was still significantly longer than that of the Can group. The hepatic tocopherol level was significantly higher in the Can group than in the hydrogenated Soy group and Soy group, but the former two groups exhibited a survival-shortening activity. These results indicate that factors other than PS, tocopherol status and fatty acid composition in some vegetable oils are critical for the survival-shortening activity observed in SHRSP rats.

Animals↗

PubMed2004

Dietary polyunsaturated fatty acids suppress acute hepatitis, alter gene expression and prolong survival of female Long-Evans Cinnamon rats, a model of Wilson disease.

In the Long-Evans Cinnamon rat, copper accumulates in the liver because of a mutation in the copper-transporting ATPase gene, and peroxidative stresses are supposed to be augmented. We examined the effects of dietary fatty acids on hepatitis, hepatic gene expression, and survival. Rats were fed a conventional, low-fat diet (CE2), a CE2 diet supplemented with 10 wt% of lard (Lar), high-linoleic soybean oil (Soy), or a mixture of docosahexaenoic acid (DHA)-rich fish oil and soybean oil (DHA/Soy). Among female rats, the mean survival times of the DHA/Soy and the Soy groups were longer by 17 approximately 20% than in the Lar and the CE2 groups. Among male rats, the survival times were much longer than in the females, but no significant difference in survival was observed among the dietary groups. Serum ceruloplasmin levels in female and male rats of all of the dietary groups were similar. Serum transaminase levels of the DHA/Soy group tended to be lower than in the CE2 group. Histological examinations revealed a marked degeneration in hepatic tissue integrity in the Lar and CE2 groups but not in the DHA/Soy group. Hepatic levels of metal-related genes, transferrin and ceruloplasmin, as well as those related to bile acid synthesis were up-regulated, and an inflammation-related gene (cyclooxygenase [COX]-2) was down-regulated in the DHA/Soy group. Some proliferation-related genes were also affected by the dietary fatty acids. These results indicate that polyunsaturated fatty acids suppress the development of acute hepatitis and prolong survival in females, regardless of whether they are of the n-6 or n-3 type, which are associated with altered gene expressions.

Acute Disease↗