Israel Ramirez

Integrated metabolic control of food intake

Inhibition of glycolysis and fatty acid oxidation by combined treatment with 2-deoxyglucose (2DG) and methyl palmoxirate, or inhibition of glycolysis and lipolysis by combined treatment with 2DG and nicotonic acid synergistically increased food intake in rats. Methyl palmoxirate treatment alone increased food intake in rats fed a high-fat, but not low-fat diet. These results provide direct evidence for a mechanism in the control of food intake that integrates signals generated by the metabolism of glucose and fatty acids. In addition, they strongly indicate a role for fatty acid oxidation in the control of eating and raise the possibility that an interaction between glucose and fat metabolism underlies the link between regulation of body fat stores and short-term food intake.

Fatty acid oxidation affects food intake by altering hepatic energy status

Inhibition of fatty acid oxidation stimulates feeding behavior in rats. To determine whether a decrease in hepatic fatty acid oxidation triggers this behavioral response, we compared the effects of different doses of methyl palmoxirate (MP), an inhibitor of fatty acid oxidation, on food intake with those on in vivo and in vitro liver and muscle metabolism. Administration of 1 mg/kg MP selectively decreased hepatic fatty acid oxidation but did not stimulate food intake. In contrast, feeding behavior increased in rats given 5 or 10 mg/kg MP, which inhibited hepatic fatty acid oxidation to the same extent as did the low dose but in addition suppressed fatty acid oxidation in muscle and produced a marked depletion of liver glycogen. Dose-related increases in food intake tracked dose-related reductions in liver ATP content, ATP-to-ADP ratio, and phosphorylation potential. The findings suggest that a decrease in hepatic fatty acid oxidation can stimulate feeding behavior by reducing hepatic energy production.Inhibition of fatty acid oxidation stimulates feeding behavior in rats. To determine whether a decrease in hepatic fatty acid oxidation triggers this behavioral response, we compared the effects of different doses of methyl palmoxirate (MP), an inhibitor of fatty acid oxidation, on food intake with those on in vivo and in vitro liver and muscle metabolism. Administration of 1 mg/kg MP selectively decreased hepatic fatty acid oxidation but did not stimulate food intake. In contrast, feeding behavior increased in rats given 5 or 10 mg/kg MP, which inhibited hepatic fatty acid oxidation to the same extent as did the low dose but in addition suppressed fatty acid oxidation in muscle and produced a marked depletion of liver glycogen. Dose-related increases in food intake tracked dose-related reductions in liver ATP content, ATP-to-ADP ratio, and phosphorylation potential. The findings suggest that a decrease in hepatic fatty acid oxidation can stimulate feeding behavior by reducing hepatic energy production.

Dietary hyperphagia in rats : role of fat, carbohydrate, and energy content

Dietary energy, fat and carbohydrate content were varied to determine the nutritional factors responsible for hyperphagia induced by feeding rats high-fat diets. In the first experiment, rats were fed isoenergetic high-fat or high-carbohydrate diets for 2 weeks. Weight gain and energy intake were lower in rats given the high-fat diet. When some of the rats were switched to a diet that was high in fat, carbohydrate and energy, gram food intake was initially unchanged, resulting in a substantial increase in energy intake and weight gain. Energy intake gradually declined over the 4 weeks following the switch to the high-energy diet. In the second experiment, rats were fed high-fat diets that were either high or low in carbohydrate content and either high or low in energy content (kcal/g). Rats fed a high-fat diet that was high in energy and carbohydrate ate the most energy and gained the most body weight and carcass fat. In the third experiment, rats were fed high-carbohydrate diets varying in fat and cellulose content. Energy intake and body weight gain varied directly as a function of caloric density regardless of the fat or cellulose content of the diets. It is concluded that hyperphagia induced by feeding high-fat diets is not due to the high dietary fat content alone. Rather, high levels of fat, carbohydrate, and energy interact to produce overeating and obesity in rats fed high-fat diets.

Chemoreception for fat: do rats sense triglycerides directly?

Rats given a choice between fluid containing 0.1-0.5% triglyceride oil and the same fluid without oil, generally preferred the fluid containing oil. Several experiments indicate that this preference is based on the detection of impurities rather than triglycerides per se. Rats preferred crude triolein to a greater degree than they did highly purified triolein or corn oil. Rats did not show any preference for or aversion to tristearin, a fat that does not decompose as readily as triolein. Rats that have been trained to avoid a dilute suspension of triolein, also avoided an aqueous extract of triolein. Since rats that had been trained to avoid triolein oil also avoided corn oil, it seems likely that different oils may possess similar impurities. Since training rats to avoid mineral oil did not reduce preference for triolein, these substances may have different flavors. It is proposed that rats use fat decomposition products to detect the presence of fats in foods.

Why do sugars taste good

The preference humans and animals show for sweet solutions has been the subject of hundreds of publications. Nevertheless, the evolutionary origin of sweet preference remains enigmatic because of the relatively low nutritional value of sugars and the absence of specific tastes for other, more essential, nutrients. Moderate concentrations of sugars are found in most plant foods because sugars play an important role in plant physiology. Widespread occurrence of sugars in plants is paralleled by widespread preference for sugar solutions in mammals. These observations suggest that preference for sugars evolved because they are common in plants and easy to detect rather than because of any special nutritional merits they offer. Perception of sweetness cannot be used to accurately meter the metabolizable energy or nutritive value of a food.

Dietary hyperphagia and obesity: what causes them?

Diets that cause animals to overeat and become obese have been used in many investigations of obesity. Most of this research, however, has concentrated on the consequences rather than the causes of overeating. Furthermore, in most studies, several nutritional variables were manipulated simultaneously, making cause and effect relationship impossible to disentangle. Consequently, progress has been slow. Diets could alter energy intake by virtue of their effects on oral-sensory, gastrointestinal or postabsorptive effects. Palatability is the most popular oralsensory hypothesis but the empirical basis for this hypothesis is particularly weak. A substantial body of evidence is consistent with the possibility that the osmotic effects of diets in the gastrointestinal tract and metabolic postabsorptive factors may play a major role in dietary hyperphagia and obesity. Suggestions for future research directions are offered.

Differential effects of medium- and long-chain triglycerides on food intake of normal and diabetic rats ☆

Three experiments were performed to examine the effect of ingestion of medium- (MCT) and long-chain (LCT) triglyceride oils at the beginning of the normal feeding period on subsequent food intake of normal and diabetic rats. In the first experiment, diabetic rats reduced food intake more than normal animals in the first 6 hr after ingestion of 2.0 ml of MCT or LCT oil. In the second experiment, diabetic rats reduced food intake to a similar extent by 6 hr after ingestion of 1.5 ml of MCT or LCT oil, but the time course of this effect depended on the oil ingested. Ingestion of MCT oil produced a decrease in food intake within 2 hr, whereas ingestion of LCT oil reduced food intake 2-4 hr later. In the third experiment, a direct comparison was made of the differential time course of food intake suppression by MCT or LCT oil in both normal and diabetic rats. Diabetic rats decreased food intake after ingestion of 1.5 ml MCT or LCT oil, whereas normal rats did not. Again, in diabetic rats, ingestion of MCT oil produced a more rapid reduction in food intake than ingestion of LCT oil. It is proposed that the more pronounced reduction in food intake of diabetic rats after oil ingestion is due to a greater degree of hepatic oxidation of ingested fat, whereas the differential effect of MCT and LCT oil ingestion in diabetic rats is due to a differential rate of delivery of the ingested lipid substrate to the liver.

Does starch taste like polycose

Rats are capable of tasting or detecting maltooligosaccharides (e.g., Polycose) and starch in water, two substances that are bland to humans. Because both substances are glucose polymers, it has been suggested that they may be detected by the same mechanism. The present experiments examined whether rats conditioned to avoid one of these substances also avoid the other. Rats were injected with lithium chloride after being allowed to drink a 3% corn starch suspension. These rats subsequently avoided corn, potato, rice, and waxy maize (high-amylopectin) starch but did not avoid 0.1-3% Polycose Rats treated with lithium chloride after ingesting 3% Polycose avoided 3% and 0.5% Polycose, but they did not avoid 3% corn starch, 6% corn starch, or 3% waxy maize starch. These results indicate that rats can discriminate between starch and Polycose (maltooligosaccharides). It therefore seems likely that Polycose and starch have different sensory qualities.

When does sucrose increase appetite and adiposity

Two methods of sucrose feeding have been employed in studies with rodents. In the nutritional method, part or all of the starch in a diet is replaced with sucrose. In the solution method, animals maintained on a nutritionally complete diet are given a sucrose solution to drink. The solution method is generally a more effective and reliable method of producing obesity except for weanling rodents. These two methods yield different results with regard to interactions with the fat and protein content of the diet, efficiency of weight gain, disaccharide effects and effects of meal feeding. It is suggested that for the nutritional method, sucrose alters food intake and adiposity via its effects on fat oxidation. For the solution method, the critical factor may be presenting a wet source of calories rather than sucrose per se. Differences in the way sucrose is fed do not account for all divergent results. Different investigators conducting similar experiments have often obtained different results. For these and other reasons, animal studies do not support the idea that sucrose intake causes obesity in humans.

Intragastric carbohydrate exerts both intake-stimulating and intake-suppressing effects.

Ingestion-contingent infusions of 6% carbohydrate did not affect saccharin intake during the first ingestive bout, but later they greatly stimulated ingestion, slowed the rate of decline of ingestion during bouts, and increased the average bout size. This suggests that the intake-stimulating effect of carbohydrate infusions is partly attributable to conditioned desatiation. Satiation can also be conditioned because more concentrated infusions (24% carbohydrate) did not increase daily intake or average bout size, even though both concentrations stimulated ingestion during the first 0.5-6.0 min of a test session, as well as during extinction tests when only water was infused. Increased intake may be partly mediated by a hedonic mechanism because naloxone, an opioid antagonist, decreased intake in rats infused with carbohydrate to a greater degree than it decreased intake in rats infused with water.