The long-term ingestion of a diet high in extra virgin olive oil produces obesity and insulin resistance but protects endothelial function in rats: a preliminary study.

BACKGROUND: It has been hypothesized that fatty acids derived from a diet high in saturated fat may negatively affect endothelial function more significantly than a diet high in unsaturated fat; nevertheless, the effects of the long-term ingestion of monounsaturated fatty acids on endothelial function have been poorly studied. METHODS: To examine the chronic effects of monounsaturated (e.g., extra virgin olive oil (EVOO)) or saturated (e.g., margarine (M)) fatty acid-rich diets on the development of insulin resistance and endothelial dysfunction in rats, three groups of rats were fed control, high-EVOO or high-M diets for 20 weeks. Body weight, energy consumption, insulin resistance, lipid peroxidation and in vitro vascular reactivity with and without metformin were assessed during the study period. RESULTS: Both high-fat diets produced obesity and insulin resistance. EVOO-fed rats showed smaller increases in total cholesterol and arterial lipid peroxidation when compared with M-fed rats. Vascular reactivity to phenylephrine and sodium nitroprusside was not modified, but the vasodilating effect of carbachol was especially reduced in the M-fed rats compared with the EVOO-fed or control groups. Metformin addition to the incubation media decreased the vascular response to phenylephrine; decrease that was lower in rats fed with both high fat diets, and increased the carbachol and nitroprusside effects, but the metformin-enhanced response to carbachol was lower in the M group. CONCLUSIONS: Our results suggest that feeding rats with high quantities of EVOO, despite producing obesity and insulin resistance, produces low levels of circulating cholesterol and arterial lipoperoxidation compared to M fed rats and shows a preserved endothelial response to carbachol, effect that is significantly enhanced by metformin only in rats fed with control and EVOO diets.

Perinatal undernutrition programmes thyroid function in the adult rat offspring.

Increasing evidence suggests that alterations in early nutrition programme physiological changes in adulthood. In the present study, we determined the effects of undernutrition during gestation and lactation on the programming of thyroid function in adult rat offspring. Perinatal undernutrition was achieved by a 40% food restriction in female Wistar rats from the mating day to weaning. On postpartum day 21, the offspring of the control and food-restricted dams were weaned and given free access to a commercial diet until adulthood. The results showed that undernourished rats exhibited decreased 3,5,3'-triiodothyronine (T3) levels but had normal thyroxine (T4) and thyrotropin (TSH) levels at weaning; on day 90, these rats displayed a significant flip, exhibiting normalised T3 (total and free) and total T4 levels, but low free T4 and persistently higher TSH levels, which were maintained even on postnatal day 140. This profile was accompanied by a scarce fat depot, a lower RMR and an exacerbated sympathetic brown adipose tissue (BAT) tone (deiodinase type 2 expression) in basal conditions. Moreover, when a functional challenge (cold exposure) was applied, the restricted group exhibited partial changes in TSH (29 v. 100%) and T4 (non-response v. 17%) levels, a significant decrease in leptin levels (75 v. 32%) and the maintenance of a sympathetic BAT over-response (higher noradrenaline levels) in comparison with the control group. The findings of the present study suggest that undernutrition during the perinatal period produces permanent changes in the hypothalamus-pituitary-thyroid axis with consequent low body weight and decreased RMR and facultative thermogenesis. We hypothesise that these changes predispose individuals to exhibiting adult subclinical hypothyroidism.

Dendritic morphology of neurons in medial prefrontal cortex, hippocampus, and nucleus accumbens in adult SH rats.

We have studied, in spontaneously hypertensive (SH) rats at different ages (2, 4, and 8 months old), the dendritic morphological changes of the pyramidal neurons of the medial prefrontal cortex (mPFC) and hippocampus and medium spiny neurons of the nucleus accumbens (NAcc) induced by the chronic effect of high-blood pressure. As control animals, we used Wistar-Kioto (WK) rats. Blood pressure was measured every 2 months to confirm the increase in arterial blood pressure. Spontaneous locomotor activity was assessed, and then brains were removed to study the dendritic morphology by the Golgi-Cox stain method followed by Sholl analysis. SH animals at 4 and 8 months of age showed decreased spine density in pyramidal neurons from the mPFC and in medium spiny cells from the NAcc. At 8 months of age as well the pyramidal neurons from the hippocampus exhibited a reduction in the number of dendritic spines. An increase in locomotion in a novel environment at all ages in the SH rats was observed. Our results indicate that high-blood pressure alters the neuronal dendrite morphology of the mPFC, hippocampus, and NAcc. The increased locomotion behavior supports the idea that dopaminergic transmission is altered in the SH rats. This could enhance our understanding of the consequences of chronic high-blood pressure on brain structure, which may implicate cognitive impairment in hypertensive patients.

Glucosamine attenuates increases of intraabdominal fat, serum leptin levels, and insulin resistance induced by a high-fat diet in rats.

The levels of circulating nonesterified fatty acids increase during obesity and contribute to insulin resistance by inhibiting insulin-stimulated glucose transport and phosphorylation in human muscles. In cells, glucose-6-phosphate is primarily used in glycogenesis and glycolysis; only 1% to 3% is converted to glucosamine-6-phosphate, which enters the hexosamine-biosynthesis pathway. The major end product of this pathway, uridine-5'-diphosphate-N-acetyl-glucosamine, which is increased by exogenous glucosamine (GlcN) administration, mediates insulin resistance. We hypothesized that the administration of GlcN to rats receiving a high-fat (HF) diet may potentiate the effects of an HF diet on glucose tolerance and other metabolic variables. To evaluate this relationship, 2 groups of rats were fed with a control or HF diet; and another 2 groups received glucosamine hydrochloride at a dose of 500 mg/kg dissolved in drinking water for 21 weeks. Metabolic variables related to insulin resistance were then measured. The levels of blood glucose and serum insulin were higher in a glucose tolerance test in the HF group as compared with the control group. Rats receiving GlcN had reduced liver glycogen and only slightly worsened glucose tolerance as compared with control rats, although this did not induce insulin resistance as evaluated by the homeostasis model assessment. Glucosamine administration was able to partially or completely inhibit some effects of the HF diet by reducing fat depot weight and serum leptin levels, thus resulting in a smaller increase in the insulinemic response to a glucose injection and lower postabsorptive glycemia.

Some metabolic effects on lactating rats of a low-energy diet restricted in good-quality protein.

Adult female Sprague-Dawley rats were fed ad libitum during pregnancy and lactation a control diet (CD; 16.1 kJ/g) or a low-energy diet with wheat gluten as the main protein source (LED; 13.3 kJ/g). Body weight, food intake, resting energy expenditure, respiratory quotient and substrate use by the mammary gland were measured. After the animals had been killed, the parametrial and retroperitoneal fat pads were weighed. The mean food intake (g) of the two groups of rats was similar, resulting in a lower energy intake by the LED rats, significantly different during the last 2 weeks of lactation. The mean body weight of both dams and pups in the LED group was lower, starting at day 9 of lactation. The resting energy expenditure increased gradually during lactation in the control group, whereas this increase was not seen in rats of the LED group in the last week of lactation. Rats that had fasted overnight had a respiratory quotient of 0.7 or less, whereas for rats that had been fed, the mean respiratory quotient was over 1.0. Under both conditions, rats showed ketonuria. The arteriovenous difference in 3-hydroxybutyrate level was higher and those for glucose, lactate and triacylglycerol were lower across the mammary glands of LED rats. The parametrial fat depot weighed less in LED rats. Reducing the increase in resting energy expenditure and using ketone bodies to a greater extent as fuels may represent important mechanisms in the LED dams to cover the energy cost of milk production.