Ovarian hormones inhibit fat intake under binge-type conditions in ovariectomized rats

Binge eating is more common in females than in males. This study investigated the effects of ovarian hormones on binge-eating behavior in a diet-related rat model. Six groups of ovariectomized Sprague-Dawley rats were used (n = 13/group). All rats had continuous access to chow and water throughout the study. One half of the rats were injected every fourth day with estradiol benzoate (2 µg/100 µl sesame oil) and progesterone (500 µg/100 µl sesame oil); the other half received only the sesame oil vehicle. Three feeding protocols were tested in each hormone injection condition: (1) chow only: no additional dietary fat access; (2) low-restriction: 1-h fat access every day; (3) high-restriction: 1-h fat access on Monday, Wednesday, and Friday. As previously reported in intact male and female rats, the high-restriction groups exhibited binge-like increases in 1-h energy intake during fat access. The major new finding of this study is that 1-h energy intake was tonically, but not cyclically, reduced in the hormone-treated high-restriction (binge) rats. Specifically, both low- and high-restriction hormone-treated rats consumed significantly less energy than did the oil-treated rats during the 1-h fat period (p < 0.0001) and overall (p < 0.0001), indicating a tonic inhibition of eating. However, food intake during the 1-h fat access period was also cyclically reduced in the hormone-treated low-restriction rats, but not in the hormone-treated high-restriction rats. These results indicate that the normal cyclic inhibitory influence of ovarian hormones on eating, but not their normal tonic inhibitory influence, is disrupted by conditions leading to binge-type eating.     

Access conditions affect binge-type shortening consumption in rats

When non-food-deprived rats are given intermittent access to certain substances, consumption of those substances is greater than when more frequent access is provided. The present study examined the effects of three different shortening access conditions on subsequent shortening intake in rats. Each of the three different shortening conditions lasted five weeks and was followed by a five-week period in which shortening access was limited by time (1 h of availability) on either an Intermittent (Monday, Wednesday, Friday) or Daily schedule of access. In Part 1, limiting the quantity of shortening provided during the 1-h period of availability attenuated subsequent 1-h shortening intake in the Intermittent access group, but had no statistically significant effect in the Daily access group. In Part 2, unrestricted availability of shortening (24 h/day-7 days/week) attenuated subsequent 1-h shortening intake in all groups. In Part 3, shortening non-availability for five weeks enhanced subsequent 1-h shortening intake in all groups. It was also shown that rats under an Intermittent, but not a Daily, schedule of access consumed as much shortening during a 1-h period of availability, as was consumed in 24 h when shortening availability was unrestricted. These results demonstrate that while intermittent access is necessary and sufficient to stimulate binge-type eating in rats, the behavioral history can modulate binge size.     

Carbohydrate intake reduces fat oxidation during exercise in obese boys

The recent surge in childhood obesity has renewed interest in studying exercise as a therapeutic means of metabolizing fat. However, carbohydrate (CHO) intake attenuates whole body fat oxidation during exercise in healthy children and may suppress fat metabolism in obese youth. To determine the impact of CHO intake on substrate utilization during submaximal exercise in obese boys, seven obese boys (mean age: 11.4 ± 1.0 year; % body fat: 35.8 ± 3.9%) performed 60 min of exercise at an intensity that approximated maximal fat oxidation. A CHO drink (CARB) or a placebo drink (CONT) was consumed in a double-blinded, counterbalanced manner. Rates of total fat, total CHO, and exogenous CHO (CHO_exo) oxidation were calculated for the last 20 min of exercise. During CONT, fat oxidation rate was 3.9 ± 2.4 mg × kg fat-free mass (FFM)⁻¹ × min⁻¹, representing 43.1 ± 22.9% of total energy expenditure (EE). During CARB, fat oxidation was lowered (p = 0.02) to 1.7 ± 0.6 mg × kg FFM⁻¹ × min⁻¹, contributing to 19.8 ± 4.9% EE. Total CHO oxidation rate was 17.2 ± 3.1 mg × kg FFM⁻¹ × min⁻¹ and 13.2 ± 6.1 mg × kg FFM⁻¹ × min⁻¹ during CARB and CONT, respectively (p = 0.06). In CARB, CHO_exo oxidation contributed to 23.3 ± 4.2% of total EE. CHO intake markedly suppresses fat oxidation during exercise in obese boys.     

Ghrelin reduces hypertonic saline intake in a variety of natriorexigenic conditions

Ghrelin is a gut peptide that has been studied extensively for its role in food intake and energy balance. More recent studies show that ghrelin reduces water intake in rats and some non-mammalian species. Despite the importance of the regulation of NaCl intake in body fluid homeostasis, the effects of ghrelin on saline intake have not been investigated. Accordingly, we tested the effect of ghrelin on water and 1.8% NaCl intake in two-bottle test conditions with the following five stimuli that increase hypertonic saline intake: central angiotensin II administration; 24 h fluid deprivation; water deprivation followed by partial rehydration; dietary sodium deficiency; and polyethylene glycol administration combined with dietary sodium deficiency. We found that ghrelin attenuated saline intake stimulated by angiotensin II, by water deprivation followed by partial rehydration and by dietary sodium deficiency. We did not detect an effect of ghrelin on saline intake after 24 h fluid deprivation without partial rehydration or after the combination of polyethylene glycol and dietary sodium deficiency. The finding that ghrelin reduced hypertonic saline intake in some, but not all, natriorexigenic conditions mirrors the previously published findings that in one-bottle tests of drinking, ghrelin reduces water intake in only some conditions. The results provide evidence for a new role for ghrelin in the regulation of body fluid homeostasis.     

Enterostatin (Val-Pro-Asp-Pro-Arg), the activation peptide of procolipase, selectively reduces fat intake

Valine-proline-aspartate-proline-arginine (VPDPR), the amino terminal pentapeptide of pancreatic procolipase, produced a dose-dependent reduction in food intake when injected intraperitoneally into Osborne-Mendel rats that had been starved overnight. This inhibition of feeding was observed when the rats were fed a high-fat diet but not in rats fed a high-carbohydrate, low-fat diet. At higher doses of VPDPR, the inhibition of feeding was maintained for over 6 hours. An equimolar mixture of the free amino acids had no effect on food intake. In rats adapted to a three-choice macronutrient diet, VPDPR inhibited fat intake but had no effect on carbohydrate or protein intake. This selective inhibition of fat intake was observed in both overnight-fasted rats presented with food and in ad-lib-fed rats at the beginning of the dark-onset feeding period. It is suggested that this peptide may be a feedback signal to regulate the intake of dietary fat.     

Physical activity, fat intake and body fat

The body fatness of a subject is a long-term reflection of the energy balance, the more intake exceeds expenditure the more energy is stored as fat. There is not yet a clear answer on the question whether the current obesity epidemic is a consequence of gluttony or sloth. Review studies do not show a reduction of physical activity over the years, and food intake is difficult to measure in daily life conditions. Food intake can only be derived from self-report, where under-reporting of food intake and selective underreporting of fat intake are major issues. Fat intake might be an important factor in the increase of body weight. Many studies suggest the capacity of the body to oxidize dietary fat is a major risk factor for a positive energy balance. Additionally, there is evidence that most of the fat consumed is stored before oxidation. Obesity prone subjects might be characterized by a higher storage of dietary fat. The only way to increase the oxidation of dietary fat, other than consuming more dietary fat, is to increase energy expenditure by an increase of physical activity. Indeed, there are indications that physical activity is an important determinant of fat oxidation. Based on the evidence presented, it is concluded that the obesity epidemic is mainly due to a high dietary intake, especially as fat, and that physical activity can be a tool to modulate the effect of fat intake on body fat.     

Naloxone reduces food intake in humans

Hypotheses generated from animal studies that the endogenous opioid system is an important modulator of food intake suggest that blockade of the system in humans should affect eating behavior. To assess this hypothesis, seven normal volunteers were given 2 mg/kg naloxone or placebo on separate days in a double-blind, random but balanced cross-over experimental design. Compared to placebo, naloxone was found to reduce significantly total food intake from preselected prepared trays served 2.75 and 7.75 hours after drug administration (p less than 0.02). The reduction was considerable (28%), and although the magnitude varied greatly among individuals, reduction occurred in each. This reduced food intake was not accompanied by a demonstrable alteration of the volunteers' perceptions of their hunger. Further cautious experimental investigation of naloxone's effects during long-term administration and in patients with eating disorders is warranted in light of its apparent effect of reducing food intake in humans while not decreasing their satiety.     

Glycerol reduces food intake in diabetic rats

Streptozotocin diabetic rats received four daily subcutaneous injections of glycerol or a glycerol solution in place of water for a seven day period. Both night and total food intake in the subcutaneous glycerol group were significantly suppressed below untreated diabetic controls. The oral glycerol group showed a nonsignificant decrease in night food intake and a significant reduction in day and total food intake. Consumption of additional fluid calories by the oral glycerol group contributed to the suppression of food intake in this group, but suppression in the subcutaneous group was unrelated to calculated calories obtained from glycerol. The oral glycerol group also consumed more of the glycerol solution than the other diabetic groups did of water. Results of this study support previous findings that subcutaneous and oral glycerol suppress food intake in normal rats although suppression with oral glycerol may have been related to caloric intake, and suggest that low plasma concentrations of insulin do not interfere with the effects obtained with glycerol in normal animals.     

Reproducibility of single- and multi-voxel 1H MRS measurements of intramyocellular lipid in overweight and lean subjects under conditions of controlled dietary calorie and fat intake

The reproducibility of repeated single-voxel 1H MRS (SV-MRS) and spectroscopic imaging (MRSI) measurements of intramyocellular lipid (IMCL) in the tibialis anterior muscle of five lean and five overweight female Caucasians, during 7 days of controlled dietary fat and calorie intake, was assessed at 1.5 T. Duplicate measures of IMCL relative to total muscle creatine (IMCL/tCr) obtained 3 days apart by both SV-MRS and MRSI correlated well (r = 0.65 and r = 0.95, respectively, P < 0.05). The coefficients of variation for repeated measures of IMCL/tCr by SV-MRS and MRSI were 24.4% and 10.7%, respectively. IMCL/tCr measured by MRSI was higher in overweight subjects than in lean subjects (8.3 +/- 3.8 vs 4.3 +/- 2.4, P < 0.05). Although both methods achieved good reproducibility in measuring IMCL in vivo, MRSI was found to offer greater flexibility and reliability, and higher sensitivity to IMCL differences, whereas SV-MRS was advantageous with respect to shorter scan time and ease of implementation.     

Changes in body fat percentage during body weight stable conditions of increased daily protein intake vs. control

Objective

The objective of this study was to examine if increased protein intake vs. control influences body fat percentage during stable body weight.

Design

Body composition was assessed before and after a 3-month isoenergetic dietary intervention of 2MJ/d supplements exchanged with 2MJ/d of habitual ad libitum energy intake. The parallel design consisted of protein-rich supplements in the protein group (n = 12) and an isoenergetic combination of carbohydrate and fat supplements in the control group (n = 12). Daily protein intake was calculated from a 24 h urinary nitrogen. Body composition was measured by a combination of underwater-weighing technique, deuterium-dilution technique and whole-body dual-energy X-ray absorptiometry (DXA), a method that allows for estimation of 4-body compartments (fat and lean; water, bone and rest).

Results

Subjects were weight stable and did not change their habitual physical activity. Daily protein intake increased in the protein group during the intervention compared to baseline with + 11 ± 14 g (P < 0.05) vs. the control group that did not change their protein intake − 1 ± 15 g. This resulted in a significant difference in protein intake during the intervention of 80 ± 21 g of the protein group vs. 59 ± 11 g of the control group (P < 0.01). Change in body fat percentage showed a significant group × time interaction of decreased body fat percentage of − 1.0 ± 1.1% of the protein group vs. 0.1 ± 0.6% of the control group (P < 0.05). The group × time interaction of change in fat mass was significant (P < 0.05), and change in fat-free mass was a trend (P = 0.05). Fat-free mass of the protein group had increased with + 0.9 ± 0.6 kg (P < 0.01), and fat mass had decreased with − 0.6 ± 0.8 kg (P < 0.05), while the control group had not changed.

Conclusion

During increased daily protein intake vs. control body fat percentage decreased with unchanged physical activity during 3 months of stable body weight.     

Central administration of zinc reduces salt intake in rats

The aim of the present study was to investigate the effect of third ventricle injections of zinc on salt intake in rats in the three different experimental models where sodium appetite is increased: fluid deprivation, central angiotensinergic stimulation and sodium depletion. Adult Wistar male rats received third ventricle injections of Zn(Ac)2 in three different doses (0.03, 0.3 and 3.0 nmol/rat). Central angiotensinergic stimulation was achieved by third ventricle injections of angiotensin II in the dose of 25 ng/rat 30 min before central zinc administration. As expected, fluid deprivation, central angiotensinergic stimulation and sodium depletion significantly increased sodium appetite. Water intake was also enhanced after fluid deprivation and central angiotensinergic stimulation. After sodium depletion, no increase in water intake was observed. Third ventricle injections of zinc inhibited salt intake in all three experimental models studied. Water intake was also inhibited by central zinc administration after fluid deprivation and central angiotensinergic stimulation. Conversely, third ventricle injections of zinc were unable to modify food intake or body temperature. It is suggested that zinc, acting on central structures related to the control of body fluid homeostasis, inhibits the drive for salt intake that is normally observed during fluid deprivation, central angiotensinergic stimulation and sodium depletion.     

Truncal vagotomy reduces food and liquid intake in man

Truncal vagotomy reduces food and liquid intake in laboratory animals but has not been studied in man. Seven (6F) morbidly obese patients kept 4-day dietary diaries with validation by urine nitrogen analysis before and 3 and 9 months after truncal vagotomy without drainage. Significant reductions in body weight were accompanied by reductions in self-reported total calorie intake from 2800 kcal/day to 1800 at 3 months and 2000 kcal/day at 9 months. The correlation between reported and validated protein intake was .72 (p less than 0.001) with a mean underreporting of protein intake by at least 27%. Macronutricant postoperative reductions in total volume and calorie density of liquid intake. Liquid calories were reduced by 47% at 3 months and 50% at 9 months and solid calories by 33% at 3 months and 27% at 9 months. It is concluded that truncal vagotomy reduces food and liquid intake in man preferentially through liquid reduction. These results have implications for surgical treatment of morbid obesity.     

Inhibition of histamine catabolism suppresses fat intake but not the intake of carbohydrates and protein

Inflammation Research -     

Lipopolysaccharide reduces sodium intake and sodium excretion in dehydrated rats

The objective of this study was to find out if lipopolysaccharide (LPS) administered intraperitoneally affects sodium and water intake and renal excretion in dehydrated rats. LPS (0.3-5 mg/kg b.w.) inhibited 0.3 M NaCl intake induced by subcutaneous injection of the diuretic furosemide (FURO, 10 mg/kg b.w.) combined with the angiotensin converting enzyme inhibitor, captopril (CAP, 5 mg/kg b.w.). Only the highest doses of LPS (2.5 and 5 mg/kg) inhibited water intake induced by FURO/CAP. LPS (0.6 mg/kg) reduced urinary volume and sodium excretion, but had no effect on mean arterial pressure or heart rate of rats treated with FURO/CAP. LPS (0.3-5.0 mg/kg) abolished intracellular thirst and reduced by 50% the urine sodium concentration of rats that received 2 ml of 2 M NaCl by gavage. LPS (0.3-5.0 mg/kg) also reduced thirst in rats treated with FURO alone (10 mg/rat sc). The results suggest that LPS has a preferential, but not exclusive, inhibitory effect on sodium intake and on intracellular thirst. The inhibition of hydro-mineral intake and the antinatriuresis caused by LPS in dehydrated rats may contribute to the multiple effects of the endotoxin on fluid and electrolyte balance and be part of the strategy to cope with infections.     

Estrogen reduces total food and carbohydrate intake,but not protein intake,in female rats

Female rats were given simultaneous access to two isocaloric, isocarbohydrate diets that contained 5% or 45% protein. During four consecutive estrous cycles, rats reduced their total food and carbohydrate intake at estrus but maintained protein intake at levels found during the other stages of the estrous cycle. Administration of estradiol benzoate (EB) to ovariectomized rats given the same 5% or 45% protein diet choices also reduced total food and carbohydrate consumption while maintaining protein consumption. By contrast, administration of EB to ovariectomized rats given isocaloric, isonitrogenous diets containing 25% or 70% carbohydrate significantly reduced both total food and carbohydrate intake. The effects of estrogen on food and protein intake reported here are similar to those previously found after administration of drugs that enhance serotoninergic neurotransmission. Thus, the effects of estrogen on nutrient selection may depend, in part, on activation of a serotoninergic mechanism.     

MTII administered peripherally reduces fat without invoking apoptosis in rats

The melanocortin (MC) system in the brain is believed to be an important downstream effector of leptin signaling; interference with MC functioning results in severe obesity. Melanotan II (MTII), an MC3/4-receptor agonist, produces similar behavioral and metabolic outcomes to those observed after leptin treatments, which enhance apoptosis in specific fat depots. To determine whether MTII also mediates adipose apoptosis induced by leptin treatment, two groups of rats (n=8) received MTII (2 mg/kg, i.p.) or saline (2 ml/kg) once daily for 4 days and had free access to food and water, and a third group was injected with saline and pair-fed (PF) to MTII treated rats. Food intake, water intake, body temperature, and body weight were measured daily. MTII reduced food and water intake and body weight gain (P<.05) and decreased body temperature compared to PF and saline-treated control groups. Retroperitoneal white adipose tissue (WAT) mass and epididymal WAT mass were reduced 46.3% and 21.1%, respectively (P<.05), after MTII, but not after PF, compared with the saline control rats. Both MTII- (25.0%) and PF (33.3%)-treated rats had decreased brown fat weight (P<.05), whereas muscle mass remained unchanged. Free fatty acid concentrations in serum were not different between MTII and control groups, but increased by 56.4% in PF group. DNA fragmentation assay did not support a role for MTII as an apoptotic signal in any of the fat tissues tested. These results show that in addition to reducing food intake and inhibiting body weight gain, intraperitoneal administration of MTII reduces fat mass, most likely by accelerated lipid mobilization, but not by apoptosis.     

Enterostatin and its target mechanisms during regulation of fat intake

A high-fat diet easily promotes hyperphagia giving an impression of an uncontrolled process. Fat digestion itself however provides control of fat intake through the digestion itself, carried out by pancreatic lipase and its protein cofactor colipase, and through enterostatin, a peptide released from procolipase during fat digestion. Procolipase (-/-) knockout mice have a severely reduced fat digestion and fat uptake, pointing to a major role of the digestive process itself. With a normal fat digestion, enterostatin basically restricts fat intake by preventing the overconsumption of fat. The mechanism for enterostatin might be an inhibition of a mu-opioid-mediated pathway, demonstrated through binding studies on SK-N-MC-cells and crude brain membranes. Another target protein of enterostatin is the beta-subunit of F1F0-ATPase, displaying a distinct binding of enterostatin, established through an aqueous two-phase partition system. The binding of enterostatin to F1-ATPase was partially displaced by beta-casomorphin, a peptide stimulating fat intake and acting competitively to enterostatin. We frame a hypothesis that regulation of fat intake through enterostatin contains a reward component, which is an F1-ATPase-mediated pathway, possibly complemented with an opioidergic pathway.     

Adrenal modulation of the enhanced fat intake subsequent to fasting

Elevations in corticosterone have been linked with the enhanced fat appetite of genetically obese Zucker rats. The present study set out to describe the effects of elevations in corticosterone in adult male Sprague-Dawley rats. Previous studies have shown that food deprivation leads to a time-dependent increase in basal corticosterone concentrations. It was predicted that rats would select a high fat diet during initial refeeding subsequent to a 24-hour fast and more severe food deprivation (48 hours) would promote greater fat consumption. Dependence upon adrenal hormones for this enhanced fat intake was examined with adrenalectomized animals. It was hypothesized that adrenalectomy would prevent the increase in fat intake seen in intact animals. Two experiments were performed. In the first, rats were given access to three separate macronutrient sources and allowed to self-select a diet for 7 days. They were then divided into groups and deprived of food for 0, 24, or 48 hours. At the end of the restriction period each rat was tail bled and macronutrient access was restored. Intakes were measured and blood samples taken at 1, 3, 6, 12, and 24 hours following restored access. During the first hour of refeeding, food-deprived animals ate significantly more fat than nondeprived animals. The enhanced fat intake was positively correlated with the elevations in corticosterone observed at the start of the refeeding period (r = .72). In the second experiment, rats were allowed to self-select a diet for 9 days. On Day 10 the rats received either bilateral adrenalectomies or sham operations.(ABSTRACT TRUNCATED AT 250 WORDS)