Advertisement
Research Article| Volume 44, SUPPLEMENT 2, 33-37, February 1995

Download started.

Ok

Serotonin and dietary fat intake: Effects of dexfenfluramine

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Traditionally, serotonin (5-HT) has been most commonly linked with carbohydrate (CHO) intake. However, in recent years it has been demonstrated that serotoninergic drugs such as dexfenfluramine also reduce energy intake and reverse body weight gain in rats exposed to weight-increasing high-fat diets. Dexfenfluramine is also effective in decreasing food intake and body weight gain of rats that gain weight on a high-fat cafeteria diet. The basic science studies indicate that serotoninergic activity—induced by dexfenfluramine—can act as a sufficient stimulus for the reduction of fat consumption. High-fat diets do not appear to impede the suppressive effect of dexfenfluramine on food intake. In human studies with dexfenfluramine, it has often been the case that the fat content of test foods has been held constant—with only protein and CHO allowed to vary. These studies therefore cannot display any direct effect on fat. However, when food choice is not limited by experimental constraints, a significant reduction of fat intake by dexfenfluramine has been demonstrated in obese patients. In other experimental studies, dexfenfluramine has suppressed fat intake to a greater extent than other macronutrients when free selection of foods has been permitted. Taken together, these studies demonstrate that dexfenfluramine is effective at reducing energy intake with a diet high in fat and may under certain conditions cause a selective avoidance of high-fat foods.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Metabolism - Clinical and Experimental
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • NACNE—National Advisory Committee for Nutrition Education
        Proposals for Nutrition Guidelines for Health Education in Britain.
        Health Education Council, London, UK1983
        • COMA—Committee on Medical Aspects of Food Policy
        Report on Health and Social Subjects. HMSO, Department of Health and Social Security, London, UK1983 (no. 28)
      1. Health of the Nation—A Strategy for Health in England. HMSO, London, UK1992
        • Dreon DM
        • Frey-Hewitt B
        • Ellsworth N
        • et al.
        Dietary fat:carbohydrate ratio and obesity in middle aged men.
        Am J Clin Nutr. 1988; 47: 995-1000
        • Tremblay A
        • Plourde G
        • Despres J-P
        • et al.
        Impact of dietary fat content and fat oxidation on energy intake in humans.
        Am J Clin Nutr. 1989; 49: 799-805
        • Romieu I
        • Willett W
        • Stampfer MJ
        • et al.
        Energy intake and other determinants of relative weight.
        Am J Clin Nutr. 1988; 47: 406-412
        • Tucker LA
        • Kano MJ
        Dietary fat and body fat: A multivariate study of 205 adult females.
        Am J Clin Nutr. 1992; 56: 616-622
        • Klesges RC
        • Klesges LM
        • Haddock CK
        • et al.
        A longitudinal analysis of the impact of dietary intake and physical activity on weight change in adults.
        Am J Clin Nutr. 1992; 55: 818-822
        • Fricker J
        • Fumeron F
        • Didier C
        • et al.
        A positive correlation between energy intake and body mass index in a population of 1312 overweight subjects.
        Int J Obes. 1989; 13: 663-681
        • Pudel V
        • Westenhoefer J
        Dietary and behavioural principles in the treatment of obesity.
        Int Monit Eating Patterns Weight Control. 1992; 1: 2-7
        • Guy-Grand B
        • Crepaldi G
        • Lefebvre P
        • et al.
        International trial of long-term dexfenfluramine in obesity.
        Lancet. Nov 11, 1989; : 1142-1145
        • Finer N
        • Finer S
        • Naoumova RP
        Drug therapy after very-low-caloric diets.
        Am J Clin Nutr. 1992; 56 (suppl): 1955-1985
        • Hill AJ
        • Blundell JE
        Sensitivity of the appetite control system in obese subjects to nutritional and serotoninergic challenges.
        Int J Obes. 1990; 14: 219-233
        • Blundell JE
        • Hill AJ
        Serotoninergic modulation of the pattern of eating and the profile of hunger-satiety in humans.
        Int J Obes. 1987; 11: 141-153
        • Blundell JE
        • Hill AJ
        Appetite control by dexfenfluramine in the treatment of obesity.
        Rev Contemp Pharmacother. 1991; 2: 79-92
        • Fernstrom JD
        • Wurtman RJ
        Brain serotonin content: Increase following ingestion of carbohydrate diet.
        Science. 1971; 174: 1023-1025
        • Wurtman RJ
        • Fernstrom JD
        Effects of diet on brain neurotransmitters.
        Nutr Rev. 1974; 32: 193-200
        • Blundell JE
        Problems and processes underlying the control of food selection and nutrient intake.
        in: Nutrition and the Brain. vol 6. Raven, New York, NY1983: 163-222
        • Blundell JE
        • Hill AJ
        Nutrition, serotonin and appetite: Case study in the evolution of a scientific idea.
        Appetite. 1987; 8: 183-194
        • Wurtman JJ
        • Wurtman RJ
        Fenfluramine and fluoxetine spare protein consumption while suppressing caloric intake by rats.
        Science. 1977; 198: 1178-1180
        • Wurtman JJ
        • Wurtman RJ
        Drugs that enhance central serotoninergic transmission diminish elective carbohydrate consumption by rats.
        Life Sci. 1979; 24: 895-904
        • Luo S
        • Li ETS
        Food intake and selection pattern of rats treated with dexfenfluramine, fluoxetine and RU24969.
        Brain Res Bull. 1990; 24: 729-733
        • Lawton CL
        • Blundell JE
        The effect of d-fenfluramine on intake of carbohydrate supplements is influenced by the hydration of the test diets.
        Behav Pharmacol. 1992; 3: 517-523
        • Lawton CL
        • Blundell JE
        5-HT and carbohydrate suppression: Effects of 5-HT antagonists on the action of d-fenfluramine and DOI.
        Pharmacol Biochem Behav. 1993; 45: 349-360
        • Kanarek RB
        Neuropharmacological approaches to studying diet selection.
        in: Kaufman S Amino Acids in Health: New Perspectives. Liss, New York, NY1987: 383-401
        • Kanarek RB
        • Dushkin H
        Serotonin administration selectively reduces fat intake in rats.
        Pharmacol Biochem Behav. 1988; 31: 113-122
        • Leibowitz SF
        • Shor-Posner G
        Brain serotonin and eating behaviour.
        Appetite. 1986; 7: 1-14
        • Sclafani A
        Animal models of obesity: Classification and characterisation.
        Int J Obes. 1984; 8: 491-508
        • Rogers PJ
        • Blundell JE
        Meal patterns and food selection during the development of obesity in rats fed a cafeteria diet.
        Neurosci Biobehav Rev. 1984; 8: 441-453
        • Prats E
        • Monfar M
        • Castella J
        • et al.
        Energy intake of rats fed a cafeteria diet.
        Physiol Behav. 1989; 45: 263-272
        • Blundell JE
        • Hill AJ
        Effect of dextrofenfluramine on feeding and bodyweight: Relationship with food composition and palatability.
        in: Vague J Guy-Grand B Björntorp P Metabolic Complications of Human Obesities. Elsevier, NordHolland, The Netherlands1985: 199-206
        • Blundell JE
        • Hill AJ
        • Kirkham TC
        Dextrofenfluramine and eating behaviour in animals: Action on food selection, motivation and body weight.
        in: Bender A Brookes LJ Human Body Weight. Pitman, London, UK1987: 233-239
        • Fisler JS
        • Underberger SJ
        • York DA
        • et al.
        d-Fenfluramine in a rat model of dietary fat—induced obesity.
        Pharmacol Biochem Behav. 1993; 45: 487-493
        • Blundell JE
        • Hill AJ
        Do serotoninergic drugs decrease energy intake by reducing fat or carbohydrate intake?.
        in: Effect of d-fenfluramine with supplemented weight-increasing diets. Pharmacol Biochem Behav. 31. 1989: 773-778
        • Wurtman J
        • Wurtman R
        • Mark S
        • et al.
        d-Fenfluramine selectively suppresses carbohydrates snacking by obese subjects.
        Int J Eating Disord. 1985; 4: 89-99
        • Wurtman JJ
        • Wurtman RJ
        • Growdon JH
        • et al.
        Carbohydrate craving in obese people: Suppression by treatments affecting serotoninergic transmission.
        Int J Eating Disord. 1982; 1: 2-15
        • Hill AJ
        • Blundell JE
        Model system for investigating the actions of anorectic drugs: Effect of d-fenfluramine on food intake, nutrient selection, food preferences, meal patterns, hunger and satiety in healthy human subjects.
        in: Ferrari E Brambilla F Advances in the BioSciences. Pergamon, Oxford, UK1986: 377-389
        • Drewnowski A
        Changes in mood after carbohydrate consumption.
        Am J Clin Nutr. 1987; 46: 703
        • Brzezinski AA
        • Wurtman JJ
        • Wurtman RJ
        • et al.
        d-Fenfluramine suppresses the increased caloric and carbohydrate intakes and improves the mood of women with pre-menstrual tension.
        Obstet Gynecol. 1990; 76: 296-301
        • Goodall EM
        • Cowen PJ
        • Franklin M
        • et al.
        Ritanserin attenuates anorectic, endocrine and thermic responses to d-fenfluramine in human volunteers.
        Psychopharmacology. 1993; 112: 461-466
        • Lafreniere F
        • Lambert J
        • Rasio E
        • et al.
        Effects of dexfenfluramine treatment on body weight and postprandial thermogenesis in obese subjects.
        in: A double-blind placebo-controlled study. Int J Obes. 17. 1993: 25-30
        • Read NW
        Role of gastrointestinal factors in hunger and satiety in man.
        in: Proc Nutr Soc. 51. 1992: 7-11
        • Lawton CL
        • Burley VJ
        • Wales JK
        • et al.
        Dietary fat and appetite control in obese subjects: Weak effects on satiation and satiety.
        Int J Obes. 1993; 17: 409-416
        • Welch I
        • Saunders K
        • Read NW
        Effect of ileal and intravenous infusions of fat emulsions on feeding and satiety in human volunteers.
        Gastroenterology. 1985; 89: 1293-1297
        • Greenberg D
        • Gibbs J
        • Smith GP
        Infusions of lipid into the duodenum elicit satiety in rats while similar infusions into the vena cava do not.
        Appetite. 1989; 12: 213
        • Greenberg D
        • Smith GP
        • Gibbs J
        Cholecystokinin and the satiating effect of fat.
        Gastroenterology. 1992; 102: 1801-1812
        • Lissner L
        • Levitsky DA
        • Strupp BJ
        • et al.
        Dietary fat and the regulation of energy intake in human subjects.
        Am J Clin Nutr. 1987; 46: 886-892
        • Blundell JE
        • Burley VJ
        • Cotton JR
        • et al.
        Dietary fat and the control of energy intake: Evaluating the effects of fat on meal size and post-meal satiety.
        Am J Clin Nutr. 1993; 57 (suppl): 7725-7785
        • Blundell JE
        Serotonin and the biology of feeding.
        Am J Clin Nutr. 1992; 55: 1555-1595
        • Stallone D
        • Nicolaidis S
        • Gibbs J
        Cholecystokinin-induced anorexia depends on serotoninergic function.
        Am J Physiol. 1989; 256: R1138-R1141
        • Poeschla B
        • Gibbs J
        • Simansky KJ
        • et al.
        Cholecystokin-induced satiety depends on activation of 5-HT1C receptors.
        Am J Physiol. 1993; 264: R62-R64
        • Neill JC
        • Cooper SJ
        Evidence that d-fenfluramine anorexia is mediated by 5-HT1 receptors.
        Psychopharmacology. 1989; 97: 213-218
        • Cooper SJ
        • Dourish CT
        • Barber DJ
        Reversal of the anorectic effect of (+) fenfluramine in the rat by the selective cholecystokinin antagonist MK-329.
        Br J Pharmacol. 1990; 99: 65-70
        • Mullen BJ
        • Martin RJ
        The effect of dietary fat on diet selection may involve central serotonin.
        Am J Physiol. 1992; 263: R559-R563