Philip M.B. Leung

Food intake: Regulation by plasma amino acid pattern

Abstract Food intake of rats fed diets containing a large amount of indispensable amino acids low in the growth limiting one was reduced 40–50% below that of the control in normal or cannulated rats infused with saline. When the growth limiting amino acid was infused, the food intake of the carotid artery-cannulated rats was not depressed, while the limiting amino acid infused into the jugular vein did not prevent the marked reduction in food intake of rats fed the imbalanced diets. These results provide evidence for a food intake regulatory function of some portion of the brain which is sensitive to the concentration of the growth limiting amino acid in blood.

Food intake and preference of olfactory bulbectomized rats fed amino acid imbalanced or deficient diets

Abstract Olfactory bulbectomy abolished the avoidance of certain artificially flavored diets fed to rats. However, olfactory bulbectomized animals markedly curtailed their food intake as did the intact controls when fed the amino acid imbalanced or deficient diet (threonine or isoleucine limited or missing) but not the corrected diet (threonine or isoleucine supplemented). Both bulbectomized and intact animals also reduced their food intake of a high protein (75% casein) diet. Bulbectomized rats, as did the intact animals, selected a protein-free diet over the imbalanced or deficient diet but chose the basal or the corrected diet over the protein-free diet. An intact olfactory bulb is thus not essential in the control of feeding in rats fed diets involving amino acid imbalance or deficiency or protein in excess.

Effects of somatostin on food intake in rats

Abstract We examined the possibility that somatostatin, a tetradecapeptide distributed in the gut and the central nervous system, may influence food intake and behavior in rats. Although intravenously infused somatostatin did not alter food intake in 8 hour fasted rats, intracerebroventricularly infused somatostatin resulted in a biphasic response, first increasing then decreasing food intake. We also observed that the effects of somatostatin vary depending upon whether animals are fed or fasted. In fed rats, food intake was decreased, while in fasted rats food intake was increased. These results suggests that somatostatin can act in the central nervous system to stimulate appetite; but that other factors, possibly related to gut motility or clearance, may inhibit further feeding once the stomach is full.

Norepinephrine and amino acids in prepyriform cortex of rats fed imbalanced amino acid diets

Monoamines and amino acids were measured in anterior prepyriform cortex (PPC) and anterior cingulate cortex (CC) of male Sprague-Dawley rats after they were offered basal, imbalanced (IMB) or corrected amino acid diets, limited in threonine (THR) or isoleucine (ILE). In the THR study, brains were taken after 2.5 hr of feeding, when intake of THR-IMB was just depressed. In the ILE study the brains were taken after 3.5 hr on ILE-IMB, a less severely imbalanced ration, before the onset of food intake depression. The PPC has been shown to be involved in the acute response of animals to imbalanced amino acid diets. In the PPC from the IMB diet groups, NE was reduced by 30%, but the other monoamines were unchanged. In CC, an area involved in the adaptive, but not the acute feeding response to imbalanced diets, the monoamines were unchanged in the IMB diet groups. In both studies, in both tissues, the limiting amino acids were decreased in the IMB groups, although the decrease of ILE in the CC failed to reach significance. The remaining indispensable amino acids, added to create the imbalance, were slightly reduced in the THR-IMB group, but not in the ILE-IMB group in both tissues. Thus, the amino acid patterns were altered in the PPC and CC, as they are in whole brains from animals fed imbalanced amino acid diets. These results also suggest that the concentration of NE in the PPC may be associated with the initial food intake response of animals to imbalanced amino acid diets.

Effect of anterior prepyriform and medial amygdaloid lesions on acquisition of taste-avoidance and response to dietary amino acid imbalance

Abstract Rats with bilateral lesions of the anterior prepyriform cortex or medial amygdala demonstrate attenuated behavioral sensitivity to a dietary threonine-imbalance. While rats with medial amygdaloid lesions demonstrate an attenuated ability to acquire taste-avoidances, such a deficit is not found in rats with lesions of the anterior prepyriform cortex. The effect of anterior prepyriform and medial amygdaloid lesions on behavioral sensitivity to dietary amino acid imbalances is discussed in terms of the probable roles played by these areas in amino acid intake control.

Effect of amygdaloid lesions on dietary intake of disproportionate amounts of amino acids

Abstract Male rats with bilateral electrolytic lesions in the anterior, medial or posterior aspects of the ventral amygdala and groups of intact rats were fed, in turn, basal, imbalanced or deficient amino acid diets involving threonine or isoleucine as the limiting amino acid, and then a low protein (6% casein) followed by a high protein (75% casein) diet. No change in food intake was observed in animals fed the threonine basal diet postoperatively. When the threonine or isoleucine imbalanced diet was substituted for the respective basal diet, animals with lesions in certain areas of the medial amygdala showed little or no depression in food intake of the imbalanced diets, while all other rats with amygdala lesions reduced their food intake markedly, as did intact controls, when fed such diets. All animals, however, curtailed their food intake of the deficient or high protein diets. The lack of responsiveness of the animals with medial amygdaloid lesions to the imbalanced diets suggests that these areas may be involved in a system regulating food intake of animals fed diets containing imbalanced amino acid mixtures.

Dietary amino acid imbalance and neurochemical changes in three hypothalamic areas

The impact of feeding imbalanced amino acid diets on monoamine, metabolite and amino acid concentrations was measured in the ventromedial hypothalamus (VMH), lateral hypothalamus (LH) and paraventricular nucleus (PVN). After rats were fed either an isoleucine imbalanced diet, a threonine imbalanced diet, or the appropriate basal or corrected control diets, regional differences were found in neurochemical concentrations. Contrary to our expectations, the limiting amino acid was unchanged in the imbalanced groups, tending to be decreased only in the isoleucine imbalanced-diet group in the PVN. This is the first report that the limiting amino acid was not reduced uniformly in the brain after imbalanced amino acid feeding. In the VMH, norepinephrine (NE) was increased by 22% and 63% in the threonine and isoleucine imbalanced-diet groups, respectively. Since the concentration of NE was affected even before the decrease in feeding, both in the VMH, and, as previously reported, in the prepyriform cortex, the NE system may be involved in very early responses to imbalanced amino acid diets.

Effect of amino acid imbalance and deficiency on dietary choice patterns of rats

Detailed dietary choice patterns were determined with a computerized feeding monitoring system in groups of Sprague Dawley rats kept on a 12:12 hr light-dark cycle and offered in sequence a series of dietary choice regimens involving amino acid-imbalanced or deficient diets with threonine as the most limiting amino acid. Animals established their preference for a threonine-basal diet over a threonine-imbalanced or a threonine-devoid (devoid of threonine) diet shortly (within 2-3 hr) after the consumption of small quantities of either diet in the beginning of the first dark-cycle. An intensive sampling process characterized by frequent small bouts was evident throughout the light period. Both the meal size and the meal frequency of the imbalanced or devoid diet were curtailed after prolonged choices. Animals preferred the threonine-corrected (imbalance corrected by threonine supplementation) over the threonine-basal diet initially with an increase in meal frequency. But no clear choice for either diet was observed thereafter. Animals did not establish their preference for the threonine-corrected diet when paired with the threonine-devoid diet until after 5 days with a steady decrease in the meal size of the devoid diet but not the meal frequency. When the protein-free diet was introduced as an alternative for the threonine-imbalanced diet, animals selected the protein-free diet during the first dark-cycle after consuming a small amount of the imbalanced diet. Initially there was a drastic reduction in meal size of the imbalanced diet and subsequently a decrease in meal frequency as well. Nevertheless, animals immediately rejected the protein-free diet and chose the threonine-basal diet when it replaced the imbalanced diet as an alternative. The almost exclusive preference for the basal diet occurred in the beginning of the first dark-cycle with an increase in meal size but no change in meal frequency. The sampling bouts of small quantities, which followed the first introduction of the diets in the choice regimens, may be an inherent investigative behavior whereby the physical or oropharyngeal properties of the diets are recognized. The establishment of the choices for the alternative diets in the present experiments provides additional information about the rapid time course of the food intake control mechanisms in rats fed amino acid-imbalanced or deficient diets.

Hyperphagia after ventral tegmental lesions and food intake responses of rats fed disproportionate amounts of dietary amino acids.

Abstract Bilateral electrolytic lesions in the ventral midbrain tegmental nucleus of male 260 g Sprague Dawley rats produced hyperphagia with a greater than 50% increase in food intake when fed a 6% casein basal diet or a threonine basal amino acid diet (balanced amino acid diet with threonine as the most limiting amino acid for growth). However, hyperphagic rats with tegmental lesions reduced their food intake drastically as compared to the intact controls when fed the threonine imbalanced or threonine devoid diet. These animals regained their hyperphagia after re-feeding with the 6% casein basal diet but again exhibited marked food intake depression and slower adaptation when fed a high protein diet (75% casein). The ventral noradrenergic bundle has been known to traverse through the ventral tegmental nucleus. The destruction or damage of this nucleus, although raising the food intake of balanced amino acid diets, did not prevent the food intake depression of rats fed diets containing imbalanced or deficient amino acid mixtures or balanced amino acid mixtures present in excess. Thus, neither the ventral tegmental nucleus nor the noradrenergic food intake inhibitory system appears to mediate the inhibition of food intake of rats fed diets containing disproportionate amounts of amino acids. Lesions placed in areas anterior to the ventral tegmental areas produced varying degress of temporary aphagia for up to 12 days when rats were fed the 6% casein diet, but normal eating was resumed with the 6% casein or the threonine basal amino acid diet. These animals showed food intake depression similar to that of the intact controls when fed the threonine imbalanced or devoid diet. Refeeding the 6% casein diet produced normal feeding once again. However, they curtailed their food intake drastically, as did the intact controls, when fed the 75% casein diet. Present results indicate that neural fibers that are reported to course through the above mentioned neural areas are not important in mediating the control of food intake of rats fed disproportionate quantities of dietary amino acids.

Effects of hippocampal lesions on adaptive intake of diets with disproportionate amounts of amino acids.

Bilateral double electrolytic overlapping lesions were placed in dorsal-lateral hippocampus of male 230 g rats, and their food intake responses to the ingestion of diets containing disproportionate amounts of amino acids were examined. Rats with such lesions and intact control rats maintained their normal intakes of the 6% casein basal diet or a threonine basal amino acid diet postoperatively. However, they exhibited marked initial food intake depression, similar to that of intact rats, when fed the threonine imbalanced amino acid diet. Also, animals with lesions in certain areas of the dorsal-lateral hippocampus showed facilitated adaptation to the amino acid imbalanced diet. Similar severe reduction in food intake with relative lack of adaptation were observed in both the intact controls and rats with hippocampal lesions when fed amino acid diets completely devoid of threonine. Initial food intake of rats with hippocampal lesions was inhibited drastically as was the case with the intact controls when fed a 75% casein high protein diet. All rats, either intact or lesioned, showed similar slow adaptation patterns with the prolonged ingestion of the high protein diet. The initial food intake responses and facilitated adaptation of the animals bearing lesions in certain areas of the hippocampus suggest that such areas are not crucially involved in the inhibition of food intake of rats fed disproportionate amounts of dietary amino acids. Rather, such areas of lesions in the hippocampus may play a role in a system governing the behavioral adaptation of the intake of amino acid imbalanced diets but not of diets containing amino acids in general excess. This would also indicate that different mechanisms control the intake of amino acid imbalanced diets and diets containing amino acids in excess.