Expression of apoptosis on rat liver by hepatic vagus hyperactivity after ventromedial hypothalamic lesioning

We examined whether the Fas (APO-1/CD95)/Fas ligand system mediates apoptosis in rats with ventromedial hypothalamus (VMH) lesions. Northern and Western blotting indicated that VMH lesions lead to a significant increase in Fas mRNA and protein expression from day 1 to day 7 and in Fas ligand mRNA and protein expression from day 2 to day 7. Immunohistochemistry indicated that the region of strongest Fas expression shifted from acinar zone 1 to zones 2 and 3 by day 7 after VMH lesioning and that at days 2-7 Fas-ligand-positive hepatocyte cell membranes and cytoplasm were randomly distributed in acinar zones 1-3. We also analyzed activation of caspase 3-like proteases in hepatocytes, Kupffer cells, and sinusoidal endothelial cells. Spectrofluorometric assay demonstrated that caspase 3-like activity significantly increased only in hepatocytes after VMH lesioning. Moreover, electron microscopy and TUNEL assay showed that VMH lesions induced apoptosis. All of these effects were completely inhibited by hepatic vagotomy and administration of atropine. Vagal firing after VMH lesioning may stimulate Fas/Fas ligand system-mediated apoptosis through the cholinergic system in the rat liver.     

Changes in glycosaminoglycan expression in the rat developing intestine

Synthesis of glycosaminoglycan (GAG) chains was studied in the developing rat intestine. Intestinal segments, taken at various developmental stages, were exposed to 3H-glucosamine and 35S-sulfate for 6 hours. The amounts of 3H-GAGs (total GAGs) and of 35S-GAGs (sulfated GAGs) showed a clear age-dependence, with a broad maximum in the fetal period when dramatic growth and morphogenesis occur. Characterization of individual GAG species indicated that hyaluronic acid (HA), heparan and chondroitin sulfate (HS and CS) synthesis was modified quantitatively or qualitatively during development: decrease of HA with age; production of undersulfated HS molecules during embryonic life; shift towards a lower hydrodynamic form of HA and HS molecules after birth. We postulate that these alterations are crucial in the elaboration of an age-related specific extracellular microenvironment allowing intestinal growth and differentiation.     

Reduced sympathetic nervous system activity in rats with ventromedial hypothalamic lesions

To determine if alterations in sympathetic nervous system (SNS) activity occur in rats with ventromedial hypothalamic (VMH) lesions, norepinephrine (NE) turnover rates were examined in various tissues of lesioned and control, weanling rats. VMH-lesioned rats fed a high-carbohydrate diet ad libitum for 4 weeks following surgery were not hyperphagic, but they gained 50% more body energy than control rats. VMH lesions extended the half-life of ³H-NE in interscapular brown adipose tissue (BAT) by 42%, in abdominal white adipose tissue (WAT) by 201%, in heart by 61% and in pancreas by 85%, and reduced total NE turnover (ng/organ/hr) in BAT (38%), WAT (57%), heart (30%) and pancreas (53%). Reduced SNS activity in BAT is consistent with the decreased energy expenditure (heat production) and increased energy efficiency observed in VMH-lesioned rats. In WAT, decreased SNS activity coupled with hyperinsulinemia would facilitate energy storage as fat by reducing lipid mobilization. In the pancreas, reduced SNS activity would contribute to hyperinsulinemia. These results support the hypothesis that VMH lesions decrease SNS activity in several organs. This change in autonomic tone is very likely a major factor in the development of obesity in VMH-lesioned animals.     

Increased hepatic triacylglycerol secretion in fasted rats with ventromedial hypothalamic lesions.

Adult female rats with lesions in the ventromedial hypothalamic area and sham-operated controls were given Triton WR 1339 intravenously after 24 h without food for measurement of liver triacylglycerol secretion rate. Tritiated water was injected for measurement of lipogenesis in liver, perirenal and subcutaneous adipose tissues in vivo. The experiments were performed on unrestrained animals with a chronically implnted venous heart cannula after 24 h without food. By the use of this technique, anesthesia and handling of the animals during the experiments was avoided. The following differences in the lesioned animals compared to the sham-operated controls were found: relative hypertriglyceridemia. A significant increase of triacylglycerol accumulation in the plasma. Increased incorporation of 3H FROM 3H20 into liver fatty acids. The experiments demonstrate that hepatic lipid synthesis during fasting is greater in the lesioned than in the control animals, but not high enough to account for the increased triacylglycerol secretion. A shift in the hepatic metabolism of fatty acids, leading to greater triacylglycerol formation at the expense of other processes is therefore suggested. The possible role of insulin in these metabolic changes is discussed.     

Lateral hypothalamic lesions and striatal dopamine levels

Rats with bilateral lateral hypothalamic lesions were killed on the third day after surgery and their brains were assayed for tel-diencephalic norepinephrine and striatal dopamine. Lesion-induced weight loss was highly correlated with depletion of striatal dopamine but not with tel-diencephalic norepinephrine. In rats with severe dopamine depletions, the degree of weight loss was related more to the striatum with the highest remaining level of dopamine suggesting that a critical level of dopamine in one striatum may be essential for lateral hypothalamic recovery.     

Combination unilateral amygdaloid and ventromedial hypothalamic lesions: evidence for a feeding pathway

Previous studies have reported hyperphagia and obesity in female rats with bilateral lesions of the most posterodorsal part of the amygdala. In rats with unilateral posterodorsal amygdaloid lesions, a dense pattern of anterograde degeneration appears in the ipsilateral ventromedial hypothalamus, but not the contralateral nucleus. In the present study, female rats with unilateral ventromedial hypothalamic lesions or sham lesions were given either sham lesions or unilateral lesions of the posterodorsal amygdala (PDA) 20 days later. Unilateral lesions of the ventromedial hypothalamus resulted in hyperphagia and excessive weight gain. Subsequent amygdaloid lesions that were contralateral to the initial hypothalamic lesions resulted in hyperphagia and additional excessive weight gains, but amygdaloid lesions ipsilateral to the initial hypothalamic lesions did not. It is concluded that the effects of the two lesions on body weight are not additive and that the PDA and ventromedial hypothalamus are part of the same ipsilateral pathway regulating feeding behavior and body weight regulation.     

大鼠局灶性脑缺血后一氧化氮合酶基因表达的变化

目的:观察大鼠局灶性脑缺血后3种类型一氧化氮合酶(NOS)mRNA表达的变化.方法:大鼠随机分为正常对照组、缺血后2、6、12、24 h组,以逆转录-聚合酶链反应(RT-PCR)法分别检测缺血脑组织NOS基因表达的变化.结果:脑缺血后eNOS、nNOSmRNA表达增强,分别于2、6 h达高峰;iNOS mRNA表达亦增高,但在缺血后12 h达高峰.结论:大鼠脑缺血早期eNOS和nNOS占主要地位,缺血后期iNOS占主要地位.