Dorothy W. Gietzen

Protein is more potent than carbohydrate for reducing appetite in rats.

The purpose of this study was to characterize further the effects of loads of protein versus carbohydrate on subsequent food intake in rats. We used an intraoral cannula to deliver isoenergetic isovolumic loads, in a tightly controlled time frame allowing for both metabolic responses and orosensory components of the load. Our results showed that the gluten load (GLT-100%) induced a greater depression in food intake than an isocaloric wheat starch load (GLT-0%). The types of protein used in the load (total milk protein vs. GLT) did not seem to influence their appetite-suppressive effect. There was a dose-dependent effect of the satiating effects of the protein loads, the GLT-100% load being more effective than either the GLT-35% or GLT-50% loads. Pattern analysis of the meal following the load suggested that animals were more satiated by protein, at least when loads contained 35% or 50% of protein, than by carbohydrate. At least 1 day was necessary before we saw a significant decrease in the energy intake following the protein loads. Thus, the animals had to learn the postingestive effects of the loads before the response stabilized. Taken together, the present results confirm that protein has a greater satiating effect than carbohydrate and extend these results by revealing that the larger the proportion of protein in the food, the larger the satiating effect, and that the quality of protein does not seem to play a significant role.

A high-protein diet enhances satiety without conditioned taste aversion in the rat

In order to determine the respective roles of conditioned food aversion, satiety and palatability, we studied behavioral responses to a 50% total milk protein diet, compared with those to a normal protein diet containing 14% total milk protein. Different paradigms were employed, including meal pattern analysis, two-choice testing, flavor testing, a behavioral satiety sequence (BSS) and taste reactivity. Our experiments showed that only behavioral and food intake parameters were disturbed during the first day when an animal ate the high-protein (P50) diet, and that most parameters returned to baseline values as soon as the second day of P50. Rats adapted to P50 did not acquire a conditioned taste aversion (CTA) but exhibited satiety, and a normal BSS. The initial reduction in high-protein diet intake appeared to result from the lower palatability of the food combined with the satiety effect of the high-protein diet and the delay required for metabolic adaptation to the higher protein level.

Dietary Preference for Sweet Foods in Patients with Dementia

Using a telephone survey, patients with probable Alzheimers disease (n = 31) and vascular dementia (n = 14) were compared with elderly normal controls (n = 43) in preferences for different foods. Patients with Alzheimers disease had a greater preference than normal controls for relatively high‐fat, sweet foods and for high‐sugar, low‐fat foods, but did not significantly differ in preference for other foods, including those high in complex carbohydrates and protein. Vascular dementia patients showed a similar pattern, not significantly different from that for Alzheimers patients. Results did not consistently support a hypothesis that increased sweet preference is a nonspecific form of disinhibited behavior related to declining mental status, nor was a hypothesis relating sweet preference to serotonin activity within the brain consistently supported. Results provide preliminary evidence that craving for sweet food may be a significant part of the clinical syndrome of dementia, but further research is needed to delineate the psychological and biological mechanisms accounting for it.

Elevated serum lactate associated with panic attacks induced by hyperventilation

Several lines of evidence suggest that lactate metabolism may be altered in panic disorder. We recently reported exaggerated increases in serum lactate in panic patients following hyperventilation during glucose infusion. In the current study, lactate metabolism was stimulated by hyperventilation following glucose ingestion in 12 panic patients and 12 controls. The seven patients who panicked during hyperventilation exhibited larger increases in serum lactate levels than nonpanicking patients or controls. The lactate response was significantly correlated with peak ratings of anxiety and panic symptoms, but not correlated with insulin or cortisol levels, heart rate, pCO2, adiposity, exercise habits, or diet. Hyperventilation-induced panic appears to be associated with metabolic changes leading to elevated serum lactate.

Cholecystokinin and serotonin receptors in the regulation of fat-induced satiety in rats

The present study investigated the relationship between endogenous CCK and serotonin (5-HT) in fat-induced satiety. Male Wistar rats with duodenal cannulas were adapted to eating 6 h/day along with receiving an infusion of saline or one of two isocaloric solutions (10 ml, 1 kcal/ml, 0.45 ml/min) varying in fat and carbohydrate content (20 or 80% energy from fat). Rats were infused 10 min after food presentation. The satiation/satiety response was determined from measures of meal size (MS), intermeal interval (IMI), and total food intake (TFI). Infusion with either fat solution reduced MS compared with saline; however, the 80% fat infusate reduced TFI and lengthened the IMI compared with saline and the 20% fat infusate. CCK and 5-HT involvement in fat-induced satiety was investigated by preceding the 80% fat infusate with CCK and/or 5-HT3 receptor antagonists Devazepide (Dev) and Tropisetron (Trop). A CCK releaser, trypsin inhibitor (TI), was added to the 20% fat infusate to enhance satiety. Pretreatment with Dev or Trop alone attenuated the inhibitory effects of the 80% solution on IMI, whereas reversal of the inhibitory effects on MS and TFI were sensitive only to Dev at the doses provided. Both antagonists together completely blocked the satiating effects of the 80% fat infusate on all feeding variables measured. Addition of TI to the 20% fat infusate lengthened the IMI but did not affect MS or TFI. These results provide evidence for the participation of both endogenous CCK and 5-HT in the satiety response to fat in the intestine.The present study investigated the relationship between endogenous CCK and serotonin (5-HT) in fat-induced satiety. Male Wistar rats with duodenal cannulas were adapted to eating 6 h/day along with receiving an infusion of saline or one of two isocaloric solutions (10 ml, 1 kcal/ml, 0.45 ml/min) varying in fat and carbohydrate content (20 or 80% energy from fat). Rats were infused 10 min after food presentation. The satiation/satiety response was determined from measures of meal size (MS), intermeal interval (IMI), and total food intake (TFI). Infusion with either fat solution reduced MS compared with saline; however, the 80% fat infusate reduced TFI and lengthened the IMI compared with saline and the 20% fat infusate. CCK and 5-HT involvement in fat-induced satiety was investigated by preceding the 80% fat infusate with CCK and/or 5-HT3 receptor antagonists Devazepide (Dev) and Tropisetron (Trop). A CCK releaser, trypsin inhibitor (TI), was added to the 20% fat infusate to enhance satiety. Pretreatment with Dev or Trop alone attenuated the inhibitory effects of the 80% solution on IMI, whereas reversal of the inhibitory effects on MS and TFI were sensitive only to Dev at the doses provided. Both antagonists together completely blocked the satiating effects of the 80% fat infusate on all feeding variables measured. Addition of TI to the 20% fat infusate lengthened the IMI but did not affect MS or TFI. These results provide evidence for the participation of both endogenous CCK and 5-HT in the satiety response to fat in the intestine.

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.

Meal pattern analysis to investigate the satiating potential of fat, carbohydrate, and protein in rats

We examined meal patterns after isocaloric duodenal infusions of fat, carbohydrate (CHO), and protein by measuring meal size, intermeal interval (IMI) and total food intake (TFI). Wistar rats were adapted to normal feeding 6 h/day, with continuous computer monitoring of feeding patterns. One of five solutions (10 ml of 1 kcal/ml at 0.45 ml/min; 0, 20, 50, 80, or 100% of energy from fat) or saline (control) was infused 10 min after initiation of eating. Separate rats received casein or casein hydrolysate at 18.5 or 37% energy. Equivalent energy loads varying in fat, CHO, and protein content compared with saline resulted in similar reductions in first meal intakes. The second meal did not differ among fat and CHO treatments including saline; however, infusion with a protein-containing solution increased the size of meal 2. The IMI was doubled by protein infusion independently of dose or source but extended dose dependently by fat. TFI was lower after high fat and higher after protein than after saline infusion. The results indicate that the concentrations of fat, CHO, and protein differentially affect the qualitative and quantitative aspects of feeding in rats.We examined meal patterns after isocaloric duodenal infusions of fat, carbohydrate (CHO), and protein by measuring meal size, intermeal interval (IMI) and total food intake (TFI). Wistar rats were adapted to normal feeding 6 h/day, with continuous computer monitoring of feeding patterns. One of five solutions (10 ml of 1 kcal/ml at 0.45 ml/min; 0, 20, 50, 80, or 100% of energy from fat) or saline (control) was infused 10 min after initiation of eating. Separate rats received casein or casein hydrolysate at 18.5 or 37% energy. Equivalent energy loads varying in fat, CHO, and protein content compared with saline resulted in similar reductions in first meal intakes. The second meal did not differ among fat and CHO treatments including saline; however, infusion with a protein-containing solution increased the size of meal 2. The IMI was doubled by protein infusion independently of dose or source but extended dose dependently by fat. TFI was lower after high fat and higher after protein than after saline infusion. The results indicate that the concentrations of fat, CHO, and protein differentially affect the qualitative and quantitative aspects of feeding in rats.

Lymphocyte Beta-Adrenoreceptor Density in Patients with Unipolar Depression and Normal Controls

Values of binding maximum (Bmax) and dissociation constant (Kd) of (-)3-[125I]iodocyanopindolol (ICYP) were determined in beta-adrenergic receptors of membranes of peripheral lymphocytes in 32 patients with unipolar depression (DSM-III-R) and 31 normal controls. Results were analyzed by a two-way Analysis of Covariance method. A significant difference was noted for group assignment (patient versus control, p less than 0.05). Mean Bmax (fmol ICYP bound/mg lymphocyte membrane fraction total protein) of patients was 31.9 +/- 3.84 (SE) and controls 46.3 +/- 3.92 (SE). A significant interaction was found between group membership and gender (p less than 0.05). In the female patient group (n = 14), mean Bmax was 30.5 +/- 5.79 (SE); in female controls, mean Bmax was 56.0 +/- 5.15 (SE). Differences between male patients and male controls were not significant. Mean values of Kd (pmol/liter) showed a trend for patient values to be lower than control values [69.0 +/- 13.66 (SE) versus 108.5 +/- 14.42 (SE), respectively]. A significant inverse relationship was noted between lymphocyte beta-receptor Bmax and frequency of panic attacks during the depressive episode in 18 patients (p = 0.05). No relationship was found between values of Kd and frequency of panic attacks in these patients. Thus, preliminary evidence is provided for relationships among altered beta-adrenergic receptor binding, gender, and indices of panic-anxiety in unipolar depressed patients.

Temporal-spatial pattern of c-fos expression in the rat brain in response to indispensable amino acid deficiency I. The initial recognition phase

Rats reduce their food intake after ingestion of a small amount of an amino acid imbalanced (AA-IMB) diet that induces a pronounced amino acid deficiency. Two hours after ingesting a threonine-IMB diet, just when food intake is depressed significantly, the concentration of threonine is decreased in some but not all brain areas. Neural recognition of this decrease in the limiting amino acid is thought to be the first step in the anorectic responses to AA-IMB diets. To identify the regions of the brain that may be activated upon recognition of an AA-IMB diet, we examined the temporal-spatial distribution of Fos immunoreactive neurons at intervals after introduction of either threonine-IMB or control diets. We found that Fos immunoreactivity in the anterior piriform cortex and immediately surrounding areas, along with the infralimbic cortex, was increased selectively early (by 2 h) after introduction of the AA-IMB diet, and remained elevated through 3 h. The anterior piriform cortex is believed to function in neural recognition of amino acid deficiency. Fos immunoreactivity in the AA-IMB group increased over the control diet groups somewhat later in the dorsomedial nucleus of the hypothalamus. We hypothesize that these areas in the rostral forebrain may serve as neural relays in the early phases of the anorectic responses that occur upon recognition of amino acid deficiency.

Behavioral and Neurochemical Changes in Folate-Deficient Mice

Weanling mice were fed an amino acid-based diet supplemented with 0 or 11.3 mumol folic acid/kg diet for approximately 38 days to study behavior and neurochemistry in folate deficiency. After approximately 5 wk, mice fed the unsupplemented diet weighted approximately 70% as much those fed the supplemented diet. After 2 wk, mice fed the unsupplemented diet consistently discarded (spilled) more food, and after approximately 5 wk, they had spilled 3 times more than mice fed the supplemented diet. Serum folate, brain folate and brain S-adenosylmethionine of mice fed the unsupplemented diet were 4, 53, and 60% as high, respectively, as those of mice fed the supplemented diet. Pathologic changes were not evident in brain, spinal cord, or skeletal muscle of folate-deficient mice. The hypothalamic 5-hydroxyindole acetic acid/serotonin ratio and caudate dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid concentrations were lower in deficient than control mice. Folate-deficient mice develop a behavioral activity, food spilling, which may have a neurochemical basis in the serotonin and dopamine systems.