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Biomedical subjects

M Apfelbaum

Publications and source records attributed to M Apfelbaum.

At least 55 records · Page 3Linked to original sources

Permanent administration of d-fenfluramine in rats: paradoxical effects.

In order to test the hypothesis of Levitzky that d-fenfluramine (d-F) acts by modifying the ponderal set-point, we compared the effects of a permanent infusion of d-F on food intake and body weight (BW). The effect on the weight persisted as long as the infusion; the clear-cut anorectic effect lasted only a few days. This paradox is compatible with the set-point hypothesis. In rats rendered overweight by insulin treatment, the d-F-induced decrease in BW was approximately four times smaller than in controls. In rats rendered overweight by a cafeteria diet, the decrease in BW was twice as large in permanently cafeteria fed rats as in cafeteria, then, ad lib fed rats. In rats rendered underweight by a restricted chow diet and then returned to an ad lib feeding, the final BW depended only on the doses of d-F (0.6 or 12 mg/kg BW/day), whatever the weight at the beginning of infusion. Thus, the underweight paradigm fits well with the set-point hypothesis; the overweight paradigm fits only partially.

Animals

Effects of a new anorectic drug (PM 170) on development of gold thioglucose-induced obesity in mice.

Gold thioglucose (GTG)-injected mice and lean mice were treated for 16 days with PM 170. The body weight and body fat were significantly increased by GTG injection and these increases in the GTG-obese group were reduced by PM 170. PM 170 also reduced food intake (16%), total body triacylglycerol (51%) and total body cholesterol (36%). Basal lipolysis of white adipose tissue, as measured by glycerol release, was stimulated by 150%. Compared to GTG-PM 170 mice, body weight gain was 2 times higher in GTG-pair-fed mice. Body fat and total body lipid content remained elevated.

Adipose Tissue

The effects of a constant T3 level and thermoneutrality in diet-induced hyperphagia.

Rats were thyroidectomized, then fitted with a miniosmotic pump infusing T3, thereby assuring a constant circulating level of T3. After a ten-day recovery period, they were submitted either to a chow or to a cafeteria diet. Body weight, food intake, and energy expenditure were recorded during a thirty day period. Thyroidectomized T3 supplemented rats did not exhibit hyperphagia when fed a cafeteria diet. Despite this puzzling normophagia, they still chose nutrients in a distribution similar to that of other cafeteria-fed rats and, though maintaining the same weight as chow-fed rats, increased their proportion of fatty weight compared to these rats. The relationship between energy expenditure, T3 concentration, and cafeteria diet are discussed.

Adipose Tissue

Effects of a moderate dietary fibre supplement on hunger rating, energy input and faecal energy output in young, healthy volunteers. A randomized, double-blind, cross-over trial.

The effects of moderate dietary-fibre supplementation on satiety, energy intake and faecal energy excretion were studied in 20 young healthy volunteers of normal body weight, mean body mass index 20.9, receiving a dietary fibre supplement of 7.3 g per day in a randomized, double-blind, cross-over study. Hunger feeling, energy intake, and defaecation pattern, were recorded daily during a 2-week control period and then, during two 4-week treatment periods. Furthermore, faecal energy output was determined during the last week of each treatment period. The fibre treatment, as compared to placebo, resulted in a significantly higher faecal energy excretion: 173 kcal/d (163-183 kcal/d) vs 153 kcal/d (135-171 kcal/d), respectively (P less than 0.05); a decrease in hunger rating (using a visual analogue scale) (P less than 0.05); an increase in number of bowel movements (P less than 0.05), and a softer consistency of the stools (P less than 0.05). There was no significant difference in mean energy intake between the two treatment periods. This study demonstrated that moderate dietary fibre supplementation in normal man increases faecal energy excretion with simultaneously decreased hunger feeling. These beneficial effects may have therapeutic value in the management of obesity.

Adult

Decreased insulin binding to adipocytes precedes both hyperinsulinemia and decreased insulin binding to erythrocytes in cafeteria-fed rats.

The relationship between food intake, obesity, insulin binding to adipocytes and erythrocytes, plasma insulin and plasma glucose was studied in an animal model of nutritional obesity--'the cafeteria-fed rats'--after 3 days, 10 days, and 3 weeks of cafeteria feeding. The antilipolytic effect of insulin was also studied. The cafeteria-fed rats ate more carbohydrates after 3 days of diet, while from the 10th day, as previously found, they ate about the same amount of carbohydrates but more lipids and increased in weight. Insulin binding to adipocytes started to decrease (P less than 0.05) 10 days after beginning the cafeteria diet despite the absence of hyperinsulinemia. This decrease in insulin binding to adipocytes was accompanied by a decrease in the responsiveness of adipocytes to the antilipolytic effect of insulin. Hyperinsulinemia (P less than 0.01) appeared only after 3 weeks. At the same time, insulin binding to erythrocytes started also to decrease (P less than 0.05). Plasma glucose levels in the cafeteria-fed rats were unchanged when compared to their controls at any time of the study. There was no correlation between body weight, plasma insulin and insulin binding, to adipocytes and to erythrocytes, at any time of the study. Thus it is possible that factors other than hyperinsulinemia could be involved in the decrease in insulin binding to both adipocytes and erythrocytes.

Adipose Tissue

Time-course, magnitude and nature of the changes induced in HDL by moderate alcohol intake in young non-drinking males.

The effects of moderate alcohol intake on the lipoprotein profile were evaluated in 10 normolipemic abstinent male subjects aged 18-21 years. The experimental period lasted 4 weeks during which 30 g of alcohol were ingested daily as red table wine. It was preceded and followed by 3 weeks of total abstinence. Lipoproteins were analyzed by gradient ultracentrifugation at the end of each abstinence period and weekly during the experimental period, to follow the time-course of alteration. Total HDL were increased by 25% (range 14-72%) during the first 2 weeks of alcohol, lighter HDL3, but not HDL2, exhibiting a greater response than other classes. The effect of alcohol regressed with time and by the 4th week mean HDL levels were only 14% higher than prior to treatment. HDL levels returned to normal on weaning. The wide variations in individual responses were consistent over the experimental period and are suggestive of differences in individual susceptibility.

Adolescent

Comparative effects of several simple carbohydrates on erythrocyte insulin receptors in obese subjects.

The effects of simple carbohydrates on erythrocyte insulin receptors, plasma insulin and plasma glucose were studied during four hypocaloric, hyperproteic, diets. One diet contained no carbohydrate; the other three contained 36 g of either glucose, galactose or fructose. These diets were given for a 14-day period to groups of moderately obese subjects. The hypocaloric carbohydrate-free diet produced a decrease in plasma insulin and glucose concentrations concomitant with an increase in the number of insulin receptors. A similar increase in insulin receptor number was found when the diet was supplemented with glucose or galactose, but not with fructose. The presence of fructose in the diet prevented any increase in insulin receptor number.

Blood Glucose

Effects of a chronic administration of two benzodiazepines on food intake in rats given a highly palatable diet.

Chronic administration of benzodiazepines is known to increase food intake in numerous species. But this effect has been studied only after a unique daily injection and over a short part of the 24 hr cycle. In the present study, during 28 days, drugs were administered to rats receiving ordinary chow or a highly palatable diet (cafeteria diet): diazepam (DZ) (2.5 mg/kg IP) twice a day, or brotizolam (BR) (1 mg/kg IP), a longer acting compound, once a day. In the chow fed rats, DZ and BR provoked a post injection hyperphagia throughout the study, followed by a compensatory hypophagia resulting in 24 hr food intakes not different from those of controls; conversely neither body weight nor weight of fat pads were increased. The cafeteria diet provoked hyperphagia and overweight. DZ did not induce any supplementary hyperphagia. BR provoked a post injection hyperphagia, also compensated in time, resulting again in 24 hr food intakes, body weight gains and weight of fat pads not increased compared to those of cafeteria controls. Thus in the rat, benzodiazepine treatment increases food intake, but only acutely, and does not provoke any trend toward obesity.

Adipose Tissue

An opioid antagonist, naltrexone, reduces preference for sucrose in humans.

Eight healthy nonobese volunteers were asked to rate, on a pleasure-displeasure scale, sucrose and salty solutions as well as alimentary and nonalimentary odors. Effects of intragastric glucose load (vs. water load) and naltrexone (vs. placebo) were tested. Naltrexone produces a significant decrease for sweetened solution on the pleasure scale, a shift even stronger than that of the glucose load itself. Such a decrease is also observed for alimentary odors but not for responses to nonalimentary stimuli. Thus the opioid system is involved in ingestive behavior in humans, and this action is perhaps specific.

Adult

[Anti-obesity activity of 3-hydroxymethyl N-methyl piperidine 4-chlorophenoxyacetate hydrochloride in mice treated with gold thioglucose].

The 3-hydroxyméthyl N-méthyl piperidine 4-chlorophenoxyacetate, hydrochloride, A, a potent anorectic, reduces weight gain of gold thioglucose obese mice through a reduced body fat and a decrease in metabolic efficiency. Compound A has much less effect in the lean mice than in the obese models. In contrast with pair-fed obese or lean mice, the decreased food consumption cannot account for all the reduced weight gain of the obese controls. Basal lipolytic activity in parametrial adipose tissue is greater in obese mice treated with A then in controls. It seems that the stimulating effect of A on lipolysis could contribute to the weight reduction.

Adipose Tissue

Action of naltrexone on the sexual impairment of obese cafeteria rats.

Two experiments were performed to explore 1) the sexual behavior of male obese cafeteria rats, 2) a possible role of endogenous opiates in the regulation of their sexual behavior. In obese cafeteria rats the proportion of ejaculators and the number of ejaculations per hour were significantly lower compared to controls. Naltrexone provoked an increase in the number of ejaculations/h both in control and cafeteria rats due to an induction of copulatory behavior in sexually inactive rats. Thus nutritional obesity provokes an impairment of sexual behavior and an injection of naltrexone (2.5 mg/Kg IP) lifts this inhibition in a similar way as in inactive, control rats.

Animals

Effects of a 'physiological' dose of triiodothyronine on obese subjects during a protein-sparing diet.

Twenty obese euthyroidian women followed an exclusively proteic diet for 18 days (74 g/day). Half received placebo, and half received 10 micrograms L-triiodothyronine. In the control group, as expected, mean weight loss was 7 percent of initial body weight; serum T3 and TSH decreased; rT3 increased; basal oxygen consumption diminished by 11 percent; nitrogen balance reached equilibrium at day 11. As compared to this group, the T3-treated group lost significantly more weight; serum T3 and TSH increased; rT3 decreased; oxygen consumption remained stable and nitrogen balance did not deteriorate. Thus, the physiological decrease in thyroid hormones provoked by a restricted diet is linked to energy expenditure but not to nitrogen balance equilibrium.

Adult

Increase of uncoupling protein and its mRNA in brown adipose tissue of rats fed on 'cafeteria diet'.

The effect of 'cafeteria diet' on mitochondrial uncoupling protein in brown adipose tissue of rats was examined. 'Cafeteria diet' induced an increase of the 32 kDa uncoupling protein in electrophoresed proteins of brown-fat mitochondria. Use of a cDNA probe corresponding to uncoupling-protein mRNA indicated that this mRNA was increased in rats fed on the 'cafeteria diet'. Nevertheless, this effect was weak compared with that observed in rats adapted to cold.

Adipose Tissue, Brown

[Incidence of lipid changes in rhegmatogenous retinal detachment, retinal vein occlusion and primary chronic glaucoma].

Several studies suggest that vascular factors may play a role in the pathogenesis of rhegmatogenous retinal detachment, retinal vein occlusion and primary chronic glaucoma. We explored the lipoprotein abnormalities in three groups of 45 patients suffering from each of these diseases compared to three control groups. We did not find significant abnormalities of cholesterol, cholesterol lipoproteins, nor Apolipoprotein B. The only significant abnormality was the presence of a higher rate of hypertriglyceridemia in the retinal vein occlusion and primary chronic glaucoma groups in comparison with their control group. In these two affections, hypertriglyceridemia should be systematically researched and treated.

Apolipoproteins B

Activation of energy expenditure in the rat by a new non-amphetaminic compound: the (4-chlorophenoxyacetate) N-methyl 3-hydroxymethyl piperidine, hydrochloride (PM 170).

The (4-chlorophenoxyacetate) N-methyl 3-hydroxymethyl piperidine, hydrochloride (PM 170), chemically unrelated to amphetamine, was studied in normal rats for any thermogenic effect. It was given in graded doses. After an acute treatment PM 170 increases energy expenditure by increasing resting oxygen consumption (VO2) and in the doses used, produced dose-related increases in VO2. Energy expenditure of rats treated for 16 days was chronically elevated, while body weight gain and food intake were reduced. It also stimulated mitochondrial oxygen consumption probably by partial uncoupling of respiration from ATP synthesis. The disruption of oxidative phosphorylation could partially explain the effect of this compound on resting metabolic rate.

Animals