High-fat diets rich in soy or fish oil distinctly alter hypothalamic insulin signaling in rats

Hypothalamic insulin inhibits food intake, preventing obesity. High-fat feeding with polyunsaturated fats may be obesogenic, but their effect on insulin action has not been elucidated. The present study evaluated insulin hypophagia and hypothalamic signaling after central injection in rats fed either control diet (15% energy from fat) or high-fat diets (50% energy from fat) enriched with either soy or fish oil. Soy rats had increased fat pad weight and serum leptin with normal body weight, serum lipid profile and peripheral insulin sensitivity. Fish rats had decreased body and fat pad weight, low leptin and corticosterone levels, and improved serum lipid profile. A 20-mU dose of intracerebroventricular (ICV) insulin inhibited food intake in control and fish groups, but failed to do so in the soy group. Hypothalamic protein levels of IR, IRS-1, IRS-2, Akt, mTOR, p70S6K and AMPK were similar among groups. ICV insulin stimulated IR tyrosine phosphorylation in control (68%), soy (36%) and fish (34%) groups. Tyrosine phosphorylation of the pp185 band was significantly stimulated in control (78%) and soy (53%) rats, but not in fish rats. IRS-1 phosphorylation was stimulated only in control rats (94%). Akt serine phosphorylation was significantly stimulated only in control (90%) and fish (78%) rats. The results showed that, rather than the energy density, the fat type was a relevant aspect of high-fat feeding, since blockade of hypothalamic insulin signal transmission and insulin hypophagia was promoted only by the high-fat soy diet, while they were preserved in the rats fed with the high-fat fish diet.     

Intestinal absorption and lymphatic transport of fish oil (MaxEPA) in the rat

Adult male, chow-fed Sprague-Dawley rats were given intraduodenally a bolus of emulsion of 0.5 ml of fish oil (MaxEPA) or olive oil plus 0.5 ml of 20 mM sodium taurocholate. Intestinal lymph was collected from a cannula in the main intestinal lymph trunk for various times after oil administration. There was no difference in the absorption of either type of oil over 6 and 24 h, over which times about 40 and 70% of the administered dose was taken up. For MaxEPA, the flux of triacylglycerols remained at a basal level of 0.07 mumol/min for 30 min, after which it rose rapidly to a maximum of 0.87 mumol/min between 90 and 120 min. The flux was 0.4 mumol/min for the subsequent 4 h. After 30 min, the composition of the lymph triacylglycerols began to change to show the presence of large proportions of fatty acyl chains that were characteristic of fish oil, especially eicosapentaenoate (20:5(n-3] and docosahexaenoate (22:6(n-3]. The composition of the lymph remained fairly similar to that of the fish oil for up to 6 h, the last time point at which detailed analysis was done. The docosahexaenoate in the triacylglycerols of the fish oil was primarily in the sn-2 position of glycerol, whereas a more random distribution of eicosapentaenoate over all glycerol positions was found. The positional distribution of the acids in the lymph triacylglycerols was similar to that in the fish oil. There was no evidence of substantial chain elongation or shortening during absorption. The results indicate that fish oil is effectively absorbed from the rat intestine without substantial alteration in the acyl chains of the triacylglycerols.     

Zinc deficiency and the activities of lipoprotein lipase in plasma and tissues of rats force-fed diets with coconut oil or fish oil

The present study was performed to investigate the effect of zinc deficiency on the activities of lipoprotein lipase in postheparin serum and tissues of rats fed diets containing either coconut oil or fish oil as dietary fat, using a bifactorial experimental design. To ensure an adequate food intake, all the rats were force-fed by gastric tube. Experimental diets contained either 0.8 mg zinc/kg (zinc-deficient diets) or 40 mg zinc/kg (zinc-adequate diets). The effects of zinc deficiency on the activities of lipoprotein lipase in postheparin serum and postprandial triglyceride concentrations and distribution of apolipoproteins in serum lipoproteins depended on the type of dietary fat. Zinc-deficient rats fed the coconut oil diet exhibited a reduced activity of lipoprotein lipase in postheparin serum and adipose tissue, markedly increased concentrations of triglycerides in serum, and a markedly reduced content of apolipoprotein C in triglyceride-rich lipoproteins and high density lipoproteins compared with zinc-adequate rats fed coconut oil. By contrast, zinc-deficient rats fed the fish oil diet did not exhibit reduced activities of lipoprotein lipase in postheparin serum and adipose tissue and increased concentrations of serum lipids compared with zinc-adequate rats fed the fish oil diet. This study suggests that a reduced activity of lipoprotein lipase might contribute to increased postprandial concentrations of serum triglycerides observed in zinc-deficient animals. However, it also demonstrates that the effects of zinc deficiency on lipoprotein metabolism are influenced by dietary fatty acids.     

Feeding diets containing 2% cheno- or urso-deoxycholic acid or cholestyramine to rats for two weeks alters intestinal morphology and bile acid absorption

This study was undertaken to examine the effect of supplementing chow for 2 weeks with 2% cheno- (CDC) or ursodeoxycholic (UDC) acid or cholestyramine (CHOL) on the intestinal morphology and in vitro uptake of bile acids in adult rats. Food intake was higher in UDC and CHOL as compared with animals fed chow or CDC, or in animals pair-fed a chow-restricted diet (CRD). Body weight gain was lower in CDC and CRD but was unchanged by feeding UDC or CHOL. Jejunal mucosal surface area was similar in the five groups, although the ileal mucosal surface area was lower in UDC than in the other animals. Feeding UDC reduced the ileal uptake of cholic acid (C), taurocholic acid (TC), and glycocholic acid (GC). Feeding CDC had no effect on bile acid uptake except when compared with animals fed a chow-restricted diet. Feeding CHOL reduced the active ileal uptake of C, had no effect on the uptake of TC or GC or CDC, and was associated with increased uptake of stearic, linoleic, and linolenic acids. These effects were likely related to a direct effect of changes in the luminal bile acids rather than due to an indirect effect of the reduced food intake, since the ileal uptake of CDC and GC was greater in animals fed CDC than in those fed a chow-restricted diet with comparable weight gain. Thus, 2 weeks of feeding bile acids or bile acid binding agents may alter the form and function of the rat intestine, and as well may lead to changes in food intake and body weight gain.     

Failure of insulin to stimulate lipogenesis and triacylglycerol secretion in perfused livers from rats adapted to dietary fish oil

Livers from male rats fed a standard commercial diet supplemented with 8% (w/w) marine fish or safflower oils were perfused for 70 min with undiluted blood in the presence and absence of insulin. Lipogenesis, as measured by the incorporation of ³H₂O into liver and perfusate fatty acids, was inhibited by the feeding of fish oil. Net triacylglycerol secretion was also depressed by this dietary treatment. Infusion of insulin stimulated triacylglycerol secretion and the incorporation of newly synthesised fatty acids into liver and perfusate lipids with dietary safflower oil but not with fish oil. Hepatic cholesterol synthesis was also depressed by feeding fish oil. Net ketogenesis was raised by feeding fish oil and was depressed by insulin with both safflower and fish oil. Blood glucose was raised in the fish oil group but with both dietary oils the hormone exerted a significant hypoglycaemic effect. The data are discussed with respect to the observations that in vivo dietary fish oil (but not safflower oil) opposes the hypertriglyceridaemia arising from the hepatic overproduction of very-low-density lipoproteins.     

Dietary fish oil delays puberty in female rats.

Marine oils contain eicosapentaenoic acid, a fatty acid that competes for cyclooxygenase and reduces the synthesis of dienoic prostanoids including prostaglandin E2 (PGE2). Since PGE2 plays an important role in the estrogen-stimulated release of hypothalamic GnRH on proestrus, it was postulated that a diet containing fish oil would delay first ovulation through inhibitory effects on GnRH release. Thirty, 22-day-old female Sprague-Dawley rats were fed a diet containing fish oil ad libitum. Controls were pair-fed an identical diet with the substitution of safflower oil as the dietary fat. All rats were killed on the morning of first metestrus after vaginal opening and the display of an estrous smear(s). Fish oil feeding did not affect growth as indicated by the lack of an observed effect on body weights or femur lengths. On the other hand, pituitary, ovarian, and uterine weights were significantly lower in the rats fed fish oil (p < 0.001). The age at first estrus of the rats fed fish oil was significantly increased compared with the controls (42.9 +/- 1.0 vs. 36.1 +/- 0.3 days; p < 0.001), whereas the number of rats with corpora lutea (CL), as well as the number of CL per ovary (2.3 +/- 0.4 vs 4.8 +/- 0.6 for controls; p < 0.001) was significantly reduced by fish oil feeding. GnRH concentration in the preoptic area/hypothalamus was significantly increased in the fish oil-fed rats (21.4 +/- 4.0 pg/mg vs. 7.6 +/- 2.2 pg/mg for controls; p < 0.01); radioimmunoassable hypothalamic PGE2 was concomitantly reduced (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma lipoprotein cholesterol and triglycerides and lipoprotein lipase activity in epididymal white adipose tissue of rats fed high sucrose or high corn oil diets

The present study was undertaken to compare plasma lipoprotein lipid composition, as well as white adipose tissue lipoprotein lipase activity, in rats fed purified diets high in either sucrose or corn oil. The experimental diets (65% of calories as sucrose or corn oil, 15% as the opposite nutrient, and 20% as casein) were given ad libitum for 4 weeks. An additional group was fed a nonpurified diet as a reference diet. Both sucrose and oil diets were spontaneously consumed in isocaloric amounts by the animals. Despite energy intakes that were 35% lower than that of the reference group, the sucrose and oil groups exhibited final body weights that were only 6 and 9% lower, respectively, than that of the reference group, and accumulated more fat in the epididymal depots. Postprandial as well as fasting total cholesterol levels were similar in the sucrose and oil groups, while the high-density lipoprotein to total cholesterol ratio was highest in the animals fed corn oil. In both the fasted and fed states, plasma total triglyceride levels were 73% higher in the sucrose group than in the corn oil group. The largest triglyceride differences due to diet were observed in the chylomicron + very-low-density lipoprotein fraction. The oil-fed rats accumulated large amounts of triglycerides in their livers. Postprandial lipoprotein lipase activity in epididymal adipose tissue was almost twice as high in the sucrose group as in the oil group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of diets high in corn oil or in extra virgin olive oil on oxidative stress in an experimental model of breast cancer

Molecular Biology Reports - Experimental evidence highlights the importance of dietetic factors on breast cancer. In this work we aimed to analyze the effects two oils, corn oil (rich in n-6...     

Corn fiber oil lowers plasma cholesterol levels and increases cholesterol excretion greater than corn oil and similar to diets containing soy sterols and soy stanols in hamsters

The aims of this study were to compare the cholesterol-lowering properties of corn fiber oil (CFO) to corn oil (CO), whether the addition of soy stanols or soy sterols to CO at similar levels in CFO would increase CO's cholesterol-lowering properties, and the mechanism(s) of action of these dietary ingredients. Fifty male Golden Syrian hamsters were divided into 5 groups of 10 hamsters each, based on similar plasma total cholesterol (TC) levels. The first group of hamsters was fed a chow-based hypercholesterolemic diet containing either 5% coconut oil + 0.24% cholesterol (coconut oil), 5% CO, 5% CFO, 5% CO + 0.6% soy sterols (sterol), or 5% CO + 0.6% soy stanols (stanol) in place of the coconut oil for 4 weeks. The stanol diet significantly inhibited the elevation of plasma TC compared to all other dietary treatments. Also, the CFO and sterol diets significantly inhibited the elevation of plasma TC compared to the CO and coconut oil diets. The CFO, sterol, and stanol diets significantly inhibited the elevation of plasma non-high density lipoprotein cholesterol compared to the CO and coconut oil diets. The stanol diet significantly inhibited the elevation of plasma high density lipoprotein cholesterol (HDL-C) compared to all other dietary treatments. The sterol diet significantly inhibited the elevation of plasma HDL-C compared to the CO and coconut oil diets, whereas the CFO diet significantly inhibited the elevation of plasma HDL-C compared to the coconut oil diet only. No differences were observed between the CFO and CO for plasma HDL-C. There were no differences observed between groups for plasma triglycerides. The CO and CFO diets had significantly less hepatic TC compared to the coconut oil, sterol, and stanol diets. The CO and CFO diets had significantly less hepatic free cholesterol compared to the sterol and stanol diets but not compared to the coconut oil diet; whereas the coconut oil and sterol diets had significantly less hepatic free cholesterol compared to the stanol diet. The CFO, sterol, and stanol diets excreted significantly more fecal cholesterol compared to the coconut oil and CO diets. In summary, CFO reduces plasma and hepatic cholesterol concentrations and increases fecal cholesterol excretion greater than CO through some other mechanism(s) in addition to increase dietary sterols and stanols-possibly oryzanols.     

Intestinal iron absorption and mucosal transferrin in rats subjected to hypoxia

Three days hypoxia (0.5 atm) increased the haemoglobin and haematocrit values in rats paralleled by enhanced intestinal iron absorption. The destination of recently-absorbed iron was primarily the erythropoietic system, viz. bone marrow, spleen and red cells. Total plasma transferrin, was increased by 30%, but no significant changes in mucosal transferrin were found. No increase in labelling of mucosal transferrin by absorbed iron was observed. These results suggest that mucosal transferrin does not play a major role in the regulation of intestinal iron absorption in hypoxia.     

Effects of dietary fish oil and corn oil on rat mammary tissue

The effects, on the maternal mammary gland, of diets containing similar lipid percentages but differing in composition of polyunsaturated fatty acids (PUFA) have been assessed in rats during pregnancy and lactation. For this purpose, tuna fish oil (an n-3-PUFA-enriched oil) and corn oil (an n-6-PUFA-enriched oil) were included in diets at ratios such that the caloric inputs were the same as that of the control diet. As expected, the maternal diet affected the tissue composition of dams. Unexpectedly, only the tuna fish oil diet had an effect on pup growth, being associated with the pups being underweight between the ages of 11 and 21 days. The maternal mammary gland of rats fed the tuna fish oil diet displayed two main modifications: the size of cytoplasmic lipid droplets was increased when compared with those in control rats and the mammary epithelium showed an unusual formation of multilayers of cells. These results show that the tuna fish oil diet, during pregnancy and lactation, exerts specific effects on mammary cells and on the formation of lipid droplets. They suggest that this maternal diet affects the functioning of the mammary tissue.     

Intestinal metabolism and absorption of cholecystokinin analogs in rats

Intestinal metabolism and poor permeability were known to be major barriers for oral absorption of large peptide drugs. Dimensionless wall permeability values of C-terminal octa- and tetra-peptides cholecystokinin analogs (CCK8 and CCK4) were estimated and found out to be greater than 1, suggesting no permeability-limited absorption for CCK analogs. Thus, a strategy employing enzyme inhibitors and a specific delivery site to improve the absorption was developed and tested with CCK8, followed by identification of metabolites of the analogs and their participating enzymes in rabbit brush-border membrane vesicles. Thiorphan and amastatin, a specific enzyme inhibitor for enkephalinase and aminopeptidase, respectively, in pH 4 buffer solution were coadministered with CCK8 to the ileum in fistulated rats. The absolute bioavailability (F) of CCK8 was 5.4% and increased to 19% in the presence of the enzyme inhibitors, while the F values following oral administration were close to zero. These results indicate that peptide oral delivery is possible.     

Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets

Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets.