Kidney lesions in copper-deficient rats

Rats fed a diet deficient in copper were found, in comparison to control rats, to have lesions in the cortex, medulla and papilla of the kidney. Within the cortex, the lesions consisted of mild atrophy of the convoluted tubules, thickening of their basement membranes and fragmentation of the reticulin framework. In the medulla and papilla, selected zones of the loop of Henle were disorganized, with their epithelia appearing atrophied and their basement membranes fragmented and irregular. The epithelial cells of the collecting tubules were atrophied and vacuolated and their basement membranes thickened. Throughout the kidney, blood vessels were distented and engorged with large numbers of erythrocytes. The most likely explanation for these lesions is vascular underperfusion which could be due to a primary effect of copper deficiency on the kidney or could be secondary to the other cardiovascular lesions that are known to occur in copper deficiency.     

Carrageenan oedema in copper-deficient rats

Carrageenan-induced hind paw oedema has been studied in rats deprived of copper for different lengths of time.A common feature observed in normally fed and copper-deficient rats was the rise of serum copper levels coccurring between 10 and 24 h after the injection of the irritant.After 1 month of copper-deficient diet no differences are seen in the oedema developed by controls and copperdeprived animals, while after 3 months the oedema developed by copper-deficient rats was significantly greater compared with the controls.These results are briefly discussed.     

Adjuvant Arthritis in young copper-deficient rats

Adjuvant arthritis has been studied in young copper-deficient rats and a very strong inhibition of the disease following 60 days of deficient diet (0.4 ppm of copper) was found. No difference in lung prostaglandin synthesis and in rat stomach strip and colon reactivity to exogenous prostaglandins was noticed between controls and copper-deficient animals.These results are briefly discussed.     

Avoidance of GABA-containing diets by olfactory bulbectomized rats

In order to test the importance of olfaction in the avoidance of GABA-containing diets by intact rats, olfactory bulbectomized and sham-operated control rats were allowed to choose between a low protein control diet and this diet supplemented with 2.5% GABA; the specificity of the response was examined by also testing for responses to other amino acids. Both groups of rats markedly avoided the GABA diet initially; the bulbectomized rats later tended to increase their intake of this diet. The bulbectomized rats chose similar amounts from the control diet and one supplemented with alanine whereas the control rats ultimately strongly preferred the latter diet. Both groups only moderately avoided a threonine-supplemented diet. The results suggest that (1) the odor of GABA is not critical in the avoidance of diets containing this amino acid; and (2) patterns of food selection from diets containing GABA differ from choices from diets containing other small neutral amino acids such as alanine or threonine.     

Self-selection of dietary casein and soy-protein by the cat

Growing specific-pathogen-free kittens were fed for two weeks a choice between two complete diets differing only in protein content. When casein diets containing 18, 36 and 54% protein were offered in the three possible combinations, the kittens consistently avoided the higher casein diets and kittens offered the two highest levels of casein significantly reduced their total food intake. In one soy-protein choice study, 16, 31 and 63% protein diets were each offered with a protein-free (PF) diet. When diets were similar in physical consistency, kittens selected similar amounts of both diets with the result that the PF:16% group consumed below their requirement of protein. In another soy-protein experiment the 16, 31 and 63% protein diets were offered in their three possible combinations. Kittens in all three groups selected similar amounts of both diets. Except for their avoidance of casein, the kittens did not regulate in a consistent manner their intake of protein and therefore, behaved very differently from the rat in the self-selection of dietary protein.     

The role of the mast cell in acute inflammatory responses of copper-deficient rats

Macromolecular leakage associated with mast cell degranulation was studied in the cremaster muscle microcirculation of copper-deficient rats. Male Sprague-Dawley rats were fed a purified diet either adequate for copper (6 g copper/gram diet) or deficient (no added copper) 4 weeks prior to experimentation. The rats were anesthetized and the cremasters (with nerve and blood supply intact) were spread in a tissue bath filled with Kreb's solution.In vivo television microscopy was used to observe the microcirculation. Intravascular fluorescein isothiocyanate conjugated to bovine serum albumin was injected and interstitial fluorescent emission intensity was used as an index of macromolecular leakage. Topical administration of the mast cell degranulator compound 48/80 (1.0 and 10.0 g/ml) induced a significantly greater macromolecular leakage in the copper-deficient animals. The compound 48/80 leakage was blocked in both groups of rats by pretreatment with diphenhydramine which is a histamine H₁ receptor blocker. Topical administration of the inflammatory mediators histamine, serotonin, and bradykinin all induced macromolecular leakage which was not significantly different between groups. These results suggest that copper deficiency increases macromolecular leakage associated with mast cell degranulation by a primary effect on the mast cell rather than on the endothelium.This material is based upon work supported by the Cooperative State Research Service, U.S. Department of Agriculture, under Agreement No. 92-37200-7676. Mention of a trademark of proprietary product does not constitute a guarantee or warranty of the product by the U.S. Department of Agriculture, and does not imply its approval to the exclusion of other products that may also be suitable.     

The effect of liver denervation on the consumption of various diets by rats

Liver afferents have been proposed to influence food intake control, however, previous studies have shown that chow (pellet) intake is apparently not altered in total liver denervated rats. The present study explored whether total liver denervation could alter the rats' intake of various diets other than chow pellets. Total liver denervations were verified using staining histological and monoamine histofluorescence techniques. The denervated and sham operated rats were given short-term (4-6 days) exposure to four diets: (diet 1, chow plus a 32% w/v sucrose-water solution; diet 2, 1:1 mixture of powdered chow and granular glucose; diet 3, 33% w/w Crisco and powdered chow mixture and diet 4, a 5% w/v glucose-water solution plus chow. Body weight gains were not affected-by either surgery or diet exposure. Daily consumptions of the diets were similar in both groups, nevertheless, there was a trend for the denervated rats to consume slightly more of a high fat diet, which lends support for one hypothesized liver satiety mechanism. Also, the denervated rats consumed less (an average 5 kcal/day) of the 5% glucose solution (one hypothesis tested would predict an increase consumption of glucose by the denervated rats). Thus the liver may play a role, albeit small, through several ill defined mechanism(s) in the regulation of feeding.     

Preference for high carbohydrate over various high fat diets by diabetic rats

Streptozotocin-diabetic male rats were hyperphagic relative to nondiabetic controls when offered only high carbohydrate (CHO) laboratory chow. Diabetics and controls ate about the same amount of high fat diets made from 67% w/w chow and 33% either coconut oil (saturated) or safflower oil (unsaturated). However, when offered a simultaneous choice of high fat diets and chow, nondiabetics and low dose (35 mg/kg) streptozotocin-diabetics showed a preference for the high fat diet: in contrast the high dose (65 mg/kg) streptozotocin diabetics developed a preference for chow. When pairs of isocaloric synthetic diets were offered, diabetics again preferred low fat/high CHO to high fat/low CHO diets, but the actual intake of fat was not constant across different diet pairs. Nondiabetics also selected away from the high fat diets in these synthetic diet pairs, even when saccharin was added to the high fat diet in an attempt to equate its sweetness with that of the paired low fat-high CHO diet. Plasma ketone levels of diabetics during obligatory high fat diet consumption were negatively correlated with their subsequent preference for the fat diet over simultaneously-offered chow. These data show that strong dietary preferences do not develop for fat in diabetics and suggest that high fat diets do not have net beneficial postingestional effects in these rats.     

Structure and function of copper-containing amine oxidases

Inflammation Research -     

High-fat diets stimulate transient hyperphagia whereas wet diets stimulate prolonged hyperphagia in Fischer rats

The effectiveness of several different kinds of diets in stimulating hyperphagia in Fischer strain rats was compared. Of three different high-fat diets examined, only one stimulated significant hyperphagia and stimulated weight gain; this diet was high in both fat and carbohydrate. However, this hyperphagia and increased weight gain was transient, lasting less than four weeks. A high-sucrose diet stimulated energy intake for only one week. In contrast, adding water to a high-starch diet or adding saccharin to a wet diet stimulated energy intake and weight gain for at least ten weeks. Once water or saccharin were removed from these diets, hyperphagia subsided or even turned into hypophagia, until body weights approached control levels. The degree of hyperphagia during the first week did not correlate with subsequent hyperphagia or weight gain. These results suggest that wet diets act by different mechanisms than do dry high-fat and high-sucrose diets.     

Hypothalamic hyperphagic rats overeat bitter sucrose octa acetate diets but not quinine diets.

Female rats were made hyperphagic with knife cuts or lesions in the ventromedial hypothalamus (VMH) and their aversion to food made bitter by adulteration with quinine or sucrose octa acetate (SOA) was examined. In short-term choice tests VMH obese rats, as well as controls, strongly preferred a 0.1% quinine diet to a 1.0% SOA diet. Yet, in 24 hr intake tests VMH obese rats overate, relative to controls, the 1% SOA diet, but underate the 0.1% quinine diet. VMH rats in both dynamic and static stages also overate SOA diets in concentrations up to 16%. However, VMH obese rats underate a 1% SOA diet when previously fed a 0.1% quinine diet. The results indicate that the VMH rat's finickiness to quinine diets may not be due to bitter taste alone, but may result from toxic postingestive effects of quinine and the development of a conditioned taste aversion.     

Immunolocalization of collagen types I, III and IV, elastin and fibronectin within the heart of normal and copper-deficient rats

Collagen types I, III and IV, fibronectin and elastin were detected by immunohistochemistry in the normal and copper-deficient rat heart. All rats maintained on a copper-deficient diet for at least 6 weeks were found to have areas of abnormal distribution of these connective tissue components within the endo- and perimysium although the normal appearance observed in control animals prevailed. It appeared that the proliferation of the fibrillar collagens and fibronectin was associated with fibrosis and scar tissue formation. In contrast, the fragmented and disorganized appearance of the myocyte basement membrane and the endomysial elastin did not seem to be associated with the fibrotic process and may be an early indication of copper deficiency. The vascular system of the copper-deficient hearts appeared normal. These results are discussed with reference to the functional and mechanical abnormalities that occur in copper-deficient animals.     

Parabrachial lesions disrupt responses of rats to amino acid devoid diets, to protein-free diets, but not to high-protein diets

Normal rats "reduce" intake of diets that lack an essential amino acid (THR-DEV), are protein free (PO%), or contain a high proportion of protein (P75%). We tested the importance of the parabrachial nuclei (PBN) in signaling such adjustments of food intake by placing electrophysiologically guided lesions in these nuclei at points that responded to gustatory stimuli. When fed the THR-DEV diet, rats with PBN lesions (PBNx) decreased their food intake significantly less than the controls (78.5 vs. 44.4%). When put on a P0% diet, PBNx animals decreased their intake only 8% compared with 23% for our CONT group. When put on a P75% diet, however, both groups decreased their intake in an equivalent amount. These experiments show that the PBN is involved in the learned aversion to an amino acid devoid diet.