Advertisement
Research Article| Volume 44, SUPPLEMENT 2, 28-32, February 1995

Effect of dexfenfluramine on fat mass distribution in a high-fat rat model

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

      Abstract

      It has been shown that in contrast to peripheral fat, visceral fat is an important risk factor for cardiovascular diseases and diabetes. In this study, we investigated whether dexfenfluramine (dF), a compound known to decrease body fat, affects fat mass differentially in various regions of the body. We used a moderately obese rat model fed a high-fat diet (40% fat). After 35 days on the diet, rats were divided into three groups: a dF-treated group ([D] 2.5 mg/kg intraperitoneally twice daily), a pair-fed group (Cp), and a control group (C) fed ad libitum. C and Cp rats were injected with saline. After 4 weeks of treatment, body fat, fat cell morphology, and metabolism were determined in subcutaneous (inguinal [ING]) and visceral (retroperitoneal [RET] and mesenteric [MES]) fat tissues. Food intake in D and Cp rats was similar, and was lower than in the C group. In comparison to Cp and C rats, D rats had lower body weight and body fat, smaller ING and RET fat pad weights, and smaller fat cell size in all depots. No significant differences were observed in fat mobilization between groups; however, fat accumulation tended to be lower in D rats. These data suggest that dF has an effect on adipose tissue independent of its effect on food intake. However, this effect seems to occur without regional specificity.

      References

        • Björntorp P
        • Rebuffé-Scrive M
        Adipose tissue distribution and function in relation to health hazards of obesity.
        in: Handbook of Eating Disorders. vol 2. Elsevier, Amsterdam, The Netherlands1988: 145-155
        • Lapidus L
        • Bengtsson C
        • Hallström T
        • et al.
        Obesity adipose tissue distribution and health in women—Results from a population study in Gothenburg, Sweden.
        Appetite. 1989; 13: 25-35
        • Larsson BK
        • Svardsudd L
        • Welin L
        • et al.
        Abdominal adipose tissue distribution, obesity and risk of cardiovascular disease and death: A 13 year follow-up of participants in the study of men born in 1913.
        Br Med J. 1984; 288: 1401-1404
        • Ohlsson LO
        • Larsson B
        • Svardsud K
        • et al.
        The influence of body fat distribution on the incidence of diabetes mellitus: 13.5 years of follow up of the participants in the study of men born in 1913.
        Diabetes. 1985; 34: 1055-1058
        • Peiris AN
        • Sothmann MS
        • Hoffmann RG
        • et al.
        Adiposity, fat distribution, and cardiovascular risk.
        Ann Intern Med. 1989; 110: 867-872
        • Fujioka S
        • Matsuzawa Y
        • Tokunaga K
        • et al.
        Contribution of intraabdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity.
        Metabolism. 1987; 34: 54-59
        • Despres JP
        • Allard C
        • Tremblay A
        • et al.
        Evidence for a regional component of body fatness in the association with serum lipids in men and women.
        Metabolism. 1985; 34: 967-973
        • Enzi GM
        • Gasparo M
        • Biondetti PR
        • et al.
        Subcutaneous and visceral fat distribution according to sex, age and overweight, evaluated by computed tomography.
        Am J Clin Nutr. 1986; 44: 739-746
        • Rebuffé-Scrive M
        Regional differences in visceral adipose tissue metabolism.
        in: Oomura Y Baba S Tarui S Recent Advances in Obesity Research. Libbey, London, UK1991: 313-316
        • Björntorp P
        The association between obesity, adipose tissue distribution and disease.
        Acta Med Scand. 1987; 723: 121-134
        • Beynen AC
        • Dekker D
        • Van Tintelen G
        • et al.
        Body composition of obese rats fed the anorectic drug dexfenfluramine.
        Nutr Rep Int. 1986; 33: 491-497
        • Fantino M
        • Faion F
        Fat mass and lipostatic activity of dexfenfluramine in rat.
        Diabete Metab. 1986; 12: 285-286
        • Brindley DN
        • Saxton J
        • Shahidullah H
        • et al.
        Possible relationships between changes in body weight set point and stress metabolism after treating rats chronically with d-fenfluramine.
        Biochem Pharmacol. 1985; 34: 1265-1267
        • De Ponte A
        • Guangnano MT
        • Giansante P
        • et al.
        The effects of d-fenfluramine on body compartments during a body weight decrease program.
        Int J Obes. 1991; 15: 29
        • Mingrone G
        • Greco AV
        • Tataranni A
        • et al.
        Effect of acute and chronic administration of d-fenfluramine on free fatty acid mobilization and oxidation.
        Int J Obes. 1992; 15: 68
        • Duhault J
        • Boulanger M
        Action de l'amphétamine et de certains de ses dérivés halogénés sur les métabolismes lipidique et glucidique.
        in: Journées Annuelles de Diabétologie de L'Hôtel-Dieu. Flammarion, Paris, France1966: 67-74
        • Andersen PH
        • Richelsen B
        • Bak J
        • et al.
        Influence of short-term dexfenfluramine therapy on glucose and lipid metabolism in obese non-diabetic patients.
        Acta Endocrinol (Copenh). 1993; 128: 251-258
        • Dannenburg WN
        • Kardian BC
        The effect of fenfluramine and methamphetamine on free fatty acid release in epididymal fat cells of the rat.
        Arch Int Pharmacodyn Ther. 1969; 177: 196-210
        • Chaouloff F
        • Gunn SM
        • Young JB
        Central 5-HT2 receptors are involved in the adrenal catecholamine-releasing and hyperglycemic effects of 5-HT indirect against d-fenfluramine in the conscious rats.
        J Pharmacol Exp Ther. 1992; 260: 1008-1016
        • Carlton J
        • Rowland NE
        Long term actions of d-fenfluramine in two rat models of obesity. I. Sustained reductions in body weight and adiposity without depletion of brain serotonin.
        Int J Obes. 1989; 13: 825-847
        • Rebuffé-Scrive M
        • Andersson B
        • Olbe L
        • et al.
        Metabolism of adipose tissue in different intraabdominal depots of non obese men and women.
        Metabolism. 1989; 38: 453-458
        • Rebuffé-Scrive M
        • Andersson B
        • Olbe L
        • et al.
        Metabolism of adipose tissue in different intraabdominal depots in severely obese men and women.
        Metabolism. 1990; 39: 1021-1025
      1. Rebuffé-Scrive M, Wyman R, Rodin J, et al: Differential distribution of catecholamines in white adipose tissue revealed by video-enhanced and confocal scanning microscopy. (submitted)

        • Fried SK
        • Kral JG
        Sex differences in regional distribution of fat cell size and lipoprotein lipase activity in morbidly obese patients.
        Int J Obes. 1987; 11: 129-140
        • Nilsson-Ehle P
        • Schotz MC
        A stable radioactive substrate emulsion for assay of lipoprotein lipase.
        J Lipid Res. 1976; 17: 536-541
        • Rebuffé-Scrive M
        • Enk L
        • Crona N
        • et al.
        Fat cell metabolism in different regions in women.
        in: Effects of menstrual cycle, pregnancy and lactation. J Clin Invest. 75. 1985: 1973-1976
        • Smith U
        • Sjötröm L
        • Björntorp P
        Comparison of two methods for determining human adipose cell size.
        J Lipid Res. 1972; 13: 822-824
        • Morgan CR
        • Lazarow A
        Immunoassay of insulin: Two antibody system.
        Diabetes. 1963; 12: 15-16
        • Even P
        • Coulaud H
        • Nicolaidis S
        Lipostatic and ischymetric mechanisms originate dexfenfluramine-induced anorexia.
        Pharmacol Biochem Behav. 1988; 30: 89-99
        • Scheurink AJW
        • Leuvenink H
        • Benthem B
        • et al.
        Dexfenfluramine treatment influences plasma catecholamines and energy substrate metabolism in rats.
        Physiol Behav. 1993; 53: 879-887
        • Brindley DN
        • Hales P
        • Al-Sieni AII
        • et al.
        Sustained decreases in weight and serum insulin, glucose, triacylglycerol and cholesterol in JCR:LA corpulent rats treated with d-fenfluramine.
        Br J Pharmacol. 1992; 105: 679-685
        • Bouchard C
        • Tremblay A
        • Després JP
        • et al.
        The response to longterm overfeeding in identical twins.
        N Engl J Med. 1990; 322: 1477-1482
        • Storlien LH
        • Thorburn AW
        • Smythe GA
        • et al.
        Effect of d-fenfluramine on basal glucose turnover and fat-feeding—induced insulin resistance in rats.
        Diabetes. 1989; 38: 499-503