Electroretinographic detection of human brain dopamine response to oral food stimulation.

OBJECTIVE: The activity of dopamine-dependent retinal signaling can be assessed using electroretinography. Response of this system to oral food stimulation might provide accessible insight into the brain dopamine response to oral stimuli as retinal dopamine concentration is dependent upon mid brain dopamine concentration was postulated. DESIGN AND METHODS: Nine individuals had cone ERG (b wave) response to oral food stimulation and oral methylphenidate (MPH) administration measured on separate days, and completed self reported eating behavior questionnaires. RESULTS: Significant and similar increases in b wave response to both stimuli (P = 0.012 and P = 0.042, MPH and food, respectively) and significant correlations of the food stimulated b wave amplitude with binge eating related behavior as measured by the Gormally Binge Eating Scale (r = 0.68, P = 0.044) and self-reported trait hunger as measured by the Stunkard and Messick Three Factor Eating Questionnaire (r = 0.67, P = 0.048) were found. CONCLUSION: The significant increase in food stimulated dopamine dependent b wave amplitude and correlation with methylphenidate stimulated b wave amplitude suggest that ERG may offer a relatively inexpensive and accessible methodology for potentially assess dopaminergic responses to food and other externally applied stimuli that have been implicated in the pathogenesis of a number of human diseases.

High-fat diet feeding elevates skeletal muscle uncoupling protein 3 levels but not its activity in rats.

OBJECTIVE: The objective of this study is to test the impact of high-fat diet (HFD) feeding on skeletal muscle (SM) uncoupling protein 3 (UCP3) expression and its association with mitochondrial ion permeability and whole-body energy homeostasis. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rats were fed ad libitum either a HFD (60% of energy from fat, n = 6) or a low-fat diet (12% of energy from fat, n = 6) for 4 weeks. Twenty-four-hour energy expenditure was measured by indirect calorimetry in the last week of the dietary treatment. Blood samples were collected for plasma leptin and free fatty acid assays, and mitochondria were isolated from hindlimb SM for subsequent determinations of UCP3 levels and mitochondrial ion permeability. RESULTS: Plasma leptin levels were higher in rats fed the HFD despite the same body weight in two groups. The same dietary treatment also rendered a 2-fold increase in plasma free fatty acid and SM UCP3 protein levels (Western blot) compared with the group fed the low-fat diet. However, the elevated UCP3 protein levels did not correlate with mitochondrial swelling rates, a measure of mitochondrial chloride, and proton permeability, or with 24-hour energy expenditure. DISCUSSION: The high correlation between the levels of plasma free fatty acid levels and SM UCP3 suggests that circulating free fatty acid may play an important role in UCP3 expression during the HFD feeding. However, the dissociation between the UCP3 protein levels and 24-hour energy expenditure as well as mitochondrial ion permeability suggests that mitochondrial proton leak mediated by muscle UCP3 may not be a major contributor in energy balance in HFD feeding, and other regulatory mechanisms independent of gene regulation may be responsible for the control of UCP3-mediated uncoupling activity.

Test meal intake in obese binge eaters in relation to mood and gender.

OBJECTIVE: We assessed test meal intake in men and women with and without binge eating disorder (BED) in relation to mood score (Zung scale). METHODS: Eighty-five overweight subjects (24 males and 61 females) participated; 30 subjects with BED and 55 without BED. Following an 8-hr fast, subjects consumed a liquid test meal until extremely full. RESULTS: BED subjects consumed significantly more (p =.009) of the test meal (1,032 g +/- 429) than the non-binge eaters (737 g +/- 399). The men ingested more than the women (p =.002). BED subjects also had higher depression scores (p =.01), without differing by gender. However, depression scores were unrelated to test meal intakes (r = -.01). DISCUSSION: The larger meal intakes of the BED group may be due to the larger stomach capacity previously found in both bulimics and obese subjects. The findings also support the premise that BED, listed in the DSM-IV appendix for further study, is found in a distinct subgroup of overweight individuals.

Gastric capacity in normal, obese, and bulimic women.

One function of the stomach is as a reservoir for food; hence, the stomach's capacity may limit the amount of food ingested. A stomach with a large capacity has been associated with bigger test meals. We compared the stomach capacity of three groups of women: normal (n=10), obese (n=11), and bulimic (n=10). Following an overnight fast, gastric capacity was estimated by filling a gastric balloon with water at 100 ml/min, with pauses for measuring intragastric pressure. One estimate was based on the maximum volume the subject could tolerate as indicated by a maximal rating of abdominal discomfort. Another estimate was based on the volume required to produce a given rise of intragastric pressure, 5 cm H(2)O. A third related measure was based on a maximal rating of fullness. Based on these estimates, the gastric capacity of the bulimics was the largest, with the obese subjects intermediate. We then separated the obese subjects according to whether they reported binge eating (n=6) or not (n=5). The gastric capacity of the binge-eating subset was similar to the bulimics, and the nonbinge-eating subset was similar to the normals. Thus, gastric capacity appears more related to binge eating behavior than to body weight.

High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects.

OBJECTIVE: To test the hypothesis that hyperinsulinemic obese subjects would respond differently to changes in the composition of hypoenergetic diets. DESIGN: A 4-week randomized dietary intervention trial. SUBJECTS: Thirteen male obese hyperinsulinemic normoglycemic subjects were divided into two groups and fed hypoenergetic diets providing 80% of their resting energy expenditure (REE). One group received a high-protein diet (HP; 45% protein, 25% carbohydrates, and 30% fat as percent of dietary energy) and the other a high-carbohydrate diet (HC; 12% protein, 58% carbohydrates and 30% fat). MEASUREMENTS: Anthropometry, body composition, fasting serum insulin and lipids, and REE were performed before and after the feeding period. RESULTS: Weight loss was higher in the HP than HC group (8.3+/-0.7 vs 6.0+/-0.6 kg, P<0. 05). There was a decrease in body fat in both groups, whereas body water decreased significantly more in the HP group. REE decreased more in the HC than the HP group (-384.3+/-84.6 vs -132.3+/-51.0 kcal, P<0.05). Serum total cholesterol, triglycerides and LDL cholesterol decreased significantly to a similar extent in both diet groups, while HDL cholesterol was decreased significantly only in the HP group. Mean fasting insulin decreased significantly in both diet groups and reached the normal range only in the HP group. CONCLUSION: A low-carbohydrate (LC), HP hypoenergetic diet could be the diet composition of choice for a weight-reducing regimen in obese hyperinsulinemic subjects.

Effects of strength or aerobic training on body composition, resting metabolic rate, and peak oxygen consumption in obese dieting subjects.

Given that resting metabolic rate (RMR) is related largely to the amount of fat-free mass (FFM), the hypothesis was that strength training, which stimulates muscle hypertrophy, would help preserve both FFM and RMR during dieting. In a randomized controlled intervention trial, moderately obese subjects (aged 19-48 y) were assigned to one of three groups: diet plus strength training, diet plus aerobic training, or diet only. Sixty-five subjects (25 men and 40 women) completed the study. They received a formula diet with an energy content of 70% of RMR or 5150 +/- 1070 kJ/d (x +/- SD) during the 8-wk intervention. They were seen weekly for individual nutritional counseling. Subjects in the two exercise groups, designed to be isoenergetic, trained three times per week under supervision. Those in the strength-training group performed progressive weight-resistance exercises for the upper and lower body. Those in the aerobic group performed alternate leg and arm cycling. After 8 wk, the mean amount of weight lost, 9.0 kg, did not differ significantly among groups. The strength-training group, however, lost significantly less FFM (P < 0.05) than the aerobic and diet-only groups. The strength-training group also showed significant increases (P < 0.05) in anthropometrically measured flexed arm muscle mass and grip strength. Mean RMR declined significantly, without differing among groups. Peak oxygen consumption increased the most for the aerobic group (P = 0.03). In conclusion, strength training significantly reduced the loss of FFM during dieting but did not prevent the decline in RMR.

Reduced stomach capacity in obese subjects after dieting.

The objective of the study was to assess the change in gastric capacity of obese subjects consuming a hypoenergetic diet. Otherwise healthy, obese subjects participated in a prospective controlled study as hospital outpatients. Fourteen (11 females, 3 males) subjects were assigned to the diet group and 9 (7 females, 2 males) were assigned to the control group. Subjects in the diet group were provided a 2508-kJ/d(600 kcal/d) formula diet for 4 wk. Subjects in the control group ate ad libitum for 4 wk. Gastric capacity was determined before the study and 4 wk later by oral insertion of a latex gastric balloon after an overnight fast. The balloon was infused with water at a rate of 100 mL/min, with pauses for measuring intragastric pressure, until no further distension was tolerated. Two indexes for estimating gastric capacity were used based on subjective and objective criteria: 1) the maximal volume that could be tolerated, and 2) the volume required to produce a rise in water pressure of 5 cm. Subjects in the diet group, who lost a mean of 9.1 kg, showed a 27% reduction in gastric capacity based on the first index (P = 0.004) and a 36% reduction based on the second index (P = 0.006). For the control subjects, gastric capacity did not change significantly with use of either index. The results demonstrate a reduction in gastric capacity in obese subjects after a restricted diet.

The relationship between daytime and nighttime food intake in an obese night-eater.

Some obese individuals consume food during awakenings from nighttime sleep. Three studies were conducted on a 28-year-old morbidly obese male with chronic sleeping complaints and insignificant weight loss, despite self-reported daily caloric restriction: I. For 3 mo, the subject recorded food intake for 24-h periods. Mean daytime intake was 1286 kcal +/- 386 (SD), and mean nighttime intake was 1036 kcal +/- 487 (SD). Caloric values of daytime and nighttime intake were negatively correlated, r = -0.22, df= 82, p < .05. II. Seven consecutive 24-h food intake recordings were obtained with an automated formula dispenser when the subject was an inpatient on a metabolic ward and received ad libitum formula as his sole food source. Mean daytime intake was 1245 +/- 662 (SD), and mean nighttime intake was 231 +/- 236 (SD). There was a non-significant negative correlation between daytime and nighttime intake, r = -0.32, df = 5, NS. III. The subject underwent polysomnographic studies on 2 non-consecutive nights, following the administration of either a low (600 kcal) or high (1800 kcal) daytime caloric condition. The subject, upon awakening from nighttime sleep, could eat from a platter of sandwich quarters placed at his bedside. The addition of 1200 kcal to daytime intake decreased nighttime intake by 654 kcal, or by 55% of the additional calories delivered during the day. The three studies (I, II, and III) show that daytime food intake can be negatively correlated with nighttime intake, and that daytime intake can influence nighttime intake in a documented obese night-eater.

Improvement of plasma lipoprotein profiles during high-flux dialysis.

Patients undergoing maintenance hemodialysis therapy have increased mortality due to cardiovascular disease. One possible etiologic factor for this increased mortality is the lipid abnormalities associated with chronic renal failure. These include elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) concentrations. Lipoprotein profiles of patients undergoing chronic hemodialysis with either saponified cellulose ester (CE) (N = 9) or polysulfone (PS) high-flux dialysis membranes (N = 10) were compared. Patients in each group received similar amounts of heparin during the dialysis. CE-dialyzed patients showed no alteration in serum TG, HDL, low-density lipoprotein, or total cholesterol when predialysis and postdialysis values were compared. PS patients, on the other hand, had a significant decrease in TG concentrations (P < 0.01) as well as a significant rise in HDL (P < 0.01). These changes might signify activation of lipoprotein lipase (LPL) during dialysis. LPL activity in PS sera was significantly greater than LPL in CE sera. Moreover, sera from PS patients inhibited LPL much less than did sera from CE patients. These findings suggest that a circulating substance not dialyzable with cellulosic membranes inhibits LPL in uremic subjects and is removed during dialysis with a PS membrane. Alternatively, the greater biocompatibility of PS may produce less LPL inhibitory cytokines during dialysis. The improvement of lipoprotein profiles in patients receiving dialysis with PS membranes may, in the long term, lead to less morbidity and mortality from atherosclerotic disease.

Gastric capacity, gastric emptying, and test-meal intake in normal and bulimic women.

The role of the stomach in regulating appetite in bulimia nervosa was examined. Subjects were nine normal and nine bulimic women of similar age, height, and weight. Gastric capacity was estimated by filling a balloon in the stomach. The mean stomach capacity of bulimic subjects was significantly larger than that of normal subjects, as revealed by the larger balloon volume tolerated (P less than 0.01) and by the larger volume needed to produce a 5 cm H2O increase in intragastric pressure (P = 0.07). The intake of a liquid meal was also significantly larger for the bulimic subjects. Gastric-emptying rate of a liquid meal was significantly delayed in the bulimic subjects during the initial 5-15 min. In all subjects, test-meal intake correlated significantly with gastric capacity (r = 0.53). In the bulimic subjects, self-reported binge intake (J) also correlated significantly with gastric capacity (r = 0.75). Binge eating in bulimic subjects may enlarge gastric capacity, which could then promote even larger binges through positive feedback.

Clinical trial of silicone-rubber gastric balloon to treat obesity.

A study was conducted to test the efficacy and safety of a 300 ml silicone-rubber gastric balloon for weight reduction. Eighty-six obese subjects were distributed into four groups: (1) gastric balloon only, (2) gastric balloon and prescribed 1000 kcal/day (239 kJ) diet, (3) 1000 kcal/day diet only, and (4) no treatment. The intervention period was 3 months. The balloon only group lost 3.2 kg +/- 0.9 (s.e.), the balloon and diet group lost 5.1 +/- 1.0 kg, the diet group lost 6.9 +/- 1.4 kg and the control group gained 0.6 +/- 0.5 kg. The three intervention groups each lost significantly more weight than the control group. The diet only group lost significantly more weight than the balloon only group. Body densitometry showed that the treatment groups lost a significant amount of body fat. Gastroscopy revealed three ulcers and two superficial erosions at balloon removal. The gastric balloons were well tolerated despite gastric spasms and nausea which abated after the initial 24-48 hours. Gastric capacity was determined in a subset of 19 subjects from the two balloon groups before the intervention by distending the stomach with a balloon and calculating the volume required to produce an increase in intragastric pressure of 5 cm H2O. Subjects with a smaller gastric capacity lost more weight with the balloon than subjects with a large capacity (r = 0.45, P less than 0.05). These results suggest that for improved efficacy, balloon volume may need to be larger than 300 ml or adjusted to the individual's gastric capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric balloon to treat obesity: a double-blind study in nondieting subjects.

To determine its efficacy and safety in treating obesity, a silicone-rubber balloon was passed into the stomach of 10 nondieting, obese subjects. In a counterbalanced sequence, the balloon was inflated with 400 mL for 1 mo and deflated for 1 mo. Lower intakes of solid and liquid test meals (NS), significantly slower gastric emptying, and concomitant changes in glucose, insulin, glucagon, and cholecystokinin concentrations consistent with slower emptying resulted during balloon inflation. After balloon inflation, one small gastric ulcer developed, which subsequently healed. Significant weight loss occurred during the second and third week of the inflation period (F[1,9] = 5.0, p less than 0.05). However, the weight loss was small and the significant effect did not continue through the fourth week.

Polysiloxane: potential noncaloric fat substitute; effects on body composition of obese Zucker rats.

Phenylmethylpolysiloxane (PS), a noncaloric, nonabsorbable liquid oil, was studied for effects on body comparison as fat substitute in the diet. Two groups of female obese Zucker rats were fed either a control low-fat (LF) or an experimental diet containing PS (22% wt/wt) incorporated into LF. Two additional groups were fed either PS or cellulose (CE) in diet providing equivalent caloric dilution. Rats on PS lost weight whereas LF control rats gained. Dissectible fat and adipocyte size of PS were smaller than those of LF. Food intake, body water, and adipocyte number did not differ between PS and LF. Body protein on PS increased only in proportion to weight. When both diets were diluted, PS animals lost more weight than CE controls despite similar food intakes, suggesting absorption of calorigenic substances derived from partial digestion of CE but not PS by intestinal microflora. Obese rats did not compensate for caloric dilution with PS.

Medium chain triglyceride in early life: effects on growth of adipose tissue.

Effects of feeding early in life a diet high in either long chain (LCT) or medium chain triglyceride (MCT) were studied on the development of adipose tissue in post-weanling rats. The diets were similar in calorie distribution and identical in nutrients except for type of fat. The caloric distribution of the two diets by percent was LCT (corn oil)/protein/carbohydrate, 70/18/12 and MCT/corn oil/protein/carbohydrate, 66/4/18/12. Male littermates with less than 5% weight difference were pair-fed the two diets randomly at age 18-20 days. One-fourth of the rats were killed at 10, 16, 22 and 28 weeks of age and analyzed for adipose depots and adipose tissue cellularity. Results showed that the LCT-fed rats were significantly heavier, with larger epididymal, retroperitoneal, omental and subcutaneous fat pads than the respective pair-fed MCT rats. Also, LCT-fed rats had larger size and number of adipocytes than MCT-fed littermates. It is concluded that the type of fat in the diet, namely LCT or MCT, when fed early in life can influence the development of adipose tissue. MCT appears less lipogenic than LCT. The mechanism for the diminished adiposity of MCT-fed rats is related to extensive oxidation of MCT and its enhancement of thermogenesis leading to lessened energy efficiency.

Role of brown adipose tissue in thermogenesis induced by overfeeding a diet containing medium chain triglyceride.

The role of brown adipose tissue in the mechanism of medium chain triglyceride (MCT)-induced thermogenesis was investigated. Under anesthesia, the interscapular brown adipose tissue (IBAT) was excised in male Sprague-Dawley rats, and the animals were fitted with gastrostomy tubes. After a 10-day recovery period, the animals were divided into two groups: one group received a diet containing MCT as 50% of calories, and the other group received an isocaloric diet containing long chain triglyceride (LCT). The diets were fed for 6 wk at a level of calorie intake that was 150% of the ad libitum intake of a parallel control group. During the last week of the study, resting and norepinephrine (NE)-stimulated O2 consumption and CO2 production were measured in a Noyons diaferometer. At the end of 6 wk, the animals were weighed and killed. The individual fat pads were dissected and weighed, and an aliquot of the right retroperitoneal fat pad was used to measure adipocyte size and number. The results showed that body weight and adipocyte size (but not adipocyte number) were significantly smaller in the MCT-fed compared to the LCT-fed animals. Resting as well as maximal NE-stimulated oxygen consumption values were significantly higher in the MCT-fed than the LCT-fed rats. It is concluded that the enhanced thermogenesis induced by MCT persists despite the absence of IBAT and that the phenomenon is likely related to more extensive oxidation of MCT- in contrast to LCT-derived fatty acids, thus leading to increased oxygen consumption, enhanced dissipation of energy as heat and diminished efficiency of weight gain and deposition of body fat.

Gastric balloon reduces food intake and body weight in obese rats.

A less invasive method than gastric reduction surgery for treating obesity was tested by inserting balloons into the stomachs of obese rats. Male Sprague-Dawley rats were placed on a high fat diet. After 4 months, the rats weighed an average of 750 g or 23% more than rats on a chow diet. Balloons were then passed orally into the stomach, inflated with 10 ml of water, and detached from the inflating tube. Eight rats had inflated balloons; six rats had no balloons. The balloons, which could be palpated, remained inflated for 12 to 49 days with a mean of 25 days. During the period of inflation, rats with balloons consumed significantly less food (p less than 0.001) relative to rats without balloons. Gastric emptying rate was significantly slowed (p less than 0.0025) in rats with inflated balloons compared to rats with balloons that had deflated and rats with no balloons. Histology of the stomachs that held inflated balloons did not reveal pathology.

Intragastric balloon reduces food intake and body weight in rats.

To test a less invasive method than gastric surgery for treating obesity, balloons were nonsurgically inserted in the stomachs of adult rats (mean wt = 537 g) for 8 wk. One group received balloons that were inflated with 7 ml of water, a second group had balloons inserted that were deflated, and a third group had no balloons inserted. Rats with inflated balloons ingested 27% less food (P less than 0.0005) during the 8 wk and weighted 16% less (P less than 0.05) at the end of this period than rats with deflated balloons or no balloons. Their food intake was significantly depressed through the 7th wk. The stomachs of the rats with inflated balloons were significantly heavier than the others with a thicker muscularis externa. Body composition was not significantly different among groups. A chronic intragastric balloon significantly reduced food intake and body weight.

Naltrexone and human eating behavior: a dose-ranging inpatient trial in moderately obese men.

To investigate the effects of the long-acting opiate antagonist naltrexone on spontaneous human eating behavior, eight moderately obese male paid volunteers were housed in a hospital metabolic unit for 28 days and offered palatable foods ad lib by a platter service method. Under double-blind conditions, equally divided doses of 100, 200 and 300 mg naltrexone, or an acetaminophen placebo, were administered twice daily in tablet form for 3-day periods each, according to a Latin Square design. The doses of naltrexone resulted in decreases of daily caloric intake from placebo level, but these reductions were neither statistically significant nor dose-related. When the averaged effects of the doses were compared to placebo, five subjects showed intake reductions but the overall intake reduction of 301.5 +/- 198.1 kcal/day (mean +/- SEM) was not statistically significant. Naltrexone administration failed to selectively alter intakes of individual meals and snacks or macronutrient consumption patterns. During active drug periods, subjects lost 0.62 +/- 0.22 lb over 3 days, while during the placebo period, subjects gained 0.46 +/- 0.68 lb. However, there was no reliable change of basal metabolic rate as a function of naltrexone administration. The present results, which indicate that naltrexone administration is relatively ineffective in reducing food intake and inducing body weight loss in obese humans, are thus in contrast with reports that administration of opiate antagonist agents promote significant reductions of food intake and attenuations of body weight gain in experimental animals.