Skip to main content Accesibility Help

A refined high carbohydrate diet is associated with changes in the serotonin pathway and visceral obesity

  • PAOLA A. SPADARO (a1), HELEN L. NAUG (a1) (a2), EUGENE F. DU TOIT (a1) (a2), DANIEL DONNER (a1) and NATALIE J. COLSON (a1) (a2)...

Consumption of palatable foods high in refined carbohydrate has been implicated as a contributing factor to the epidemic levels of obesity. Such foods may disrupt appetite regulation in the hypothalamus through alterations in hunger and satiety signalling. This investigation examined whether a palatable high refined carbohydrate (HRC) diet with the potential to induce obesity was linked to modulation of serotonin and dopamine signalling within the hypothalamus of rats. Male Wistar rats were allowed ad libitum access to either a palatable refined carbohydrate enriched (HRC) diet or standard chow (SC). Visceral fat percentage was used as a measure of the animals' weight gain during the trial. Real-time PCR was applied to determine any variation in levels of expression of the serotonin (Slc6A4 or Sert) and dopamine transporter (Slc6A3 or Dat) genes. After 29 weeks, the HRC group showed a significant increase in visceral fat percentage accompanied by increased expression of Sert. Higher levels of circulating triglycerides were also seen. This investigation determined that a refined high carbohydrate diet is associated with visceral obesity, increased circulating lipids in the blood and distorted serotonergic signalling, which possibly alters satiety and hunger signals.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      A refined high carbohydrate diet is associated with changes in the serotonin pathway and visceral obesity
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      A refined high carbohydrate diet is associated with changes in the serotonin pathway and visceral obesity
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      A refined high carbohydrate diet is associated with changes in the serotonin pathway and visceral obesity
      Available formats
Corresponding author
*Corresponding author: Natalie J. Colson, Menzies Health Institute of Queensland School of Medical Science, Griffith University Gold Coast Campus, Griffith University, Qld, Australia, 4222. Tel: +61 7 55529075. Fax: +61 7 55528908. E-mail:
Hide All
Alsio, J., Olszewski, P. K., Levine, A. S. & Schioth, H. B. (2012). Feed-forward mechanisms: addiction-like behavioral and molecular adaptations in overeating. Frontiers in Neuroendocrinology 33, 127139.
Alsio, J., Pickering, C., Roman, E., Hulting, A. L., Lindblom, J. & Schioth, H. B. (2009). Motivation for sucrose in sated rats is predicted by low anxiety-like behavior. Neuroscience Letters 454, 193197.
Avena, N. M. & Bocarsly, M. E. (2012). Dysregulation of brain reward systems in eating disorders: neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa. Neuropharmacology 63, 8796.
Avena, N. M., Rada, P. & Hoebel, B. G. (2008). Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neuroscience and Bio-behavioral Reviews 32, 2039.
Barson, J. R., Karatayev, O., Gaysinskaya, V., Chang, G. Q. & Leibowitz, S. F. (2012). Effect of dietary fatty acid composition on food intake, triglycerides, and hypothalamic peptides. Regulatory Peptides 173, 1320.
Berthoud, H. R., Munzberg, H., Richards, B. K. & Morrison, C. D. (2012). Neural and metabolic regulation of macronutrient intake and selection. The Proceedings of the Nutrition Society 71, 390400.
Bocarsly, M. E., Powell, E. S., Avena, N. M. & Hoebel, B. G. (2010). High-fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels. Pharmacology, Biochemistry, and Behavior 97, 101106.
Bonefeld, B. E., Elfving, B. & Wegener, G. (2008). Reference genes for normalization: a study of rat brain tissue. Synapse 62, 302309.
Cansell, C., Castel, J., Denis, R. G., Rouch, C., Delbes, A. S., Martinez, S., Mestivier, D., Finan, B., Maldonado-Aviles, J. G., Rijnsburger, M., Tschöp, M. H., DiLeone, R. J., Eckel, R. H., la Fleur, S. E., Magnan, C., Hnasko, T. S. & Luquet, S. (2014). Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding. Molecular Psychiatry 19, 10951105.
Crane, J. D., Palanivel, R., Mottillo, E. P., Bujak, A. L., Wang, H., Ford, R. J., Collins, A., Blumer, R. M., Fullerton, M. D., Yabut, J. M., Kim, J. J., Ghia, J. E., Hamza, S. M., Morrison, K. M., Schertzer, J. D., Dyck, J. R., Khan, W. I. & Steinberg, G. R. (2015). Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Nature Medicine 21, 166172.
Daws, L. C. & Gould, G. G. (2011). Ontogeny and regulation of the serotonin transporter: providing insights into human disorders. Pharmacology Therapeutics 131, 6179.
Donovan, M. H. & Tecott, L. H. (2013). Serotonin and the regulation of mammalian energy balance. Frontiers in Neuroscience 7, 36.
du Toit, E. F., Smith, W., Muller, C., Strijdom, H., Stouthammer, B., Woodiwiss, A. J., Norton, G. R. & Lochner, A. (2008). Myocardial susceptibility to ischemic-reperfusion injury in a prediabetic model of dietary-induced obesity. American Journal of Physiology Heart and Circulatory Physiology 294, H2336H2343.
Emiliano, A. B., Cruz, T., Pannoni, V. & Fudge, J. L. (2007). The interface of oxytocin-labeled cells and serotonin transporter-containing fibers in the primate hypothalamus: a substrate for SSRIs therapeutic effects? Neuropsychopharmacology 32, 977988.
Erlanson-Albertsson, C. (2005). How palatable food disrupts appetite regulation. Basic & Clinical Pharmacology & Toxicology 97, 6173.
Fernstrom, J. D., Munger, S. D., Sclafani, A., de Araujo, I. E., Roberts, A. & Molinary, S. (2012). Mechanisms for sweetness. The Journal of Nutrition 142, 1134S1141S.
Garfield, A. S. & Heisler, L. K. (2009). Pharmacological targeting of the serotonergic system for the treatment of obesity. The Journal of Physiology 587, 4960.
Goncalves, P., Araujo, J. R. & Martel, F. (2008). The effect of high glucose on SERT, the human plasmalemmal serotonin transporter. Nutritional Neuroscience 11, 244250.
Grabenhorst, F., Rolls, E. T., Parris, B. A. & d'Souza, A. A. (2010). How the brain represents the reward value of fat in the mouth. Cerebral Cortex 20, 10821091.
Harchaoui, K. E., Visser, M. E., Kastelein, J. J., Stroes, E. S. & Dallinga-Thie, G. M. (2009). Triglycerides and cardiovascular risk. Current Cardiology Reviews 5, 216222.
Homberg, J. R., la Fleur, S. E. & Cuppen, E. (2010). Serotonin transporter deficiency increases abdominal fat in female, but not male rats. Obesity 18, 137145.
Jijun, L., Zaiwang, L., Anyuan, L., Shuzhen, W., Fanghua, Q., Lin, Z. & Hong, L. (2010). Abnormal expression of dopamine and serotonin transporters associated with the pathophysiologic mechanism of Tourette syndrome. Neurology India 58, 523529.
Johnston, W. L. & Glanville, N. T. (1994). Acute dietary PCPA treatment decreases the KD of brain [3H]5-HT binding in rainbow trout, Oncorhynchus mykiss, fed a high carbohydrate diet. Comparative Biochemistry, Physiology, Pharmacology, Toxicology and Endocrinology. 107, 455461.
Jorgensen, H., Riis, M., Knigge, U., Kjaer, A. & Warberg, J. (2003). Serotonin receptors involved in vasopressin and oxytocin secretion. Journal of Neuroendocrinology 15, 242249.
Kempadoo, K. A., Tourino, C., Cho, S. L., Magnani, F., Leinninger, G. M., Stuber, G. D., Zhang, F., Myers, M. G., Deisseroth, K., de Lecea, L. & Bonci, A. (2013). Hypothalamic neurotensin projections promote reward by enhancing glutamate transmission in the VTA. The Journal of Neuroscience 33, 76187626.
King, B. M. (2013). The modern obesity epidemic, ancestral hunter-gatherers, and the sensory/reward control of food intake. American Psychology 68, 8896.
Koskela, A. K., Kaurijoki, S., Pietilainen, K. H., Karhunen, L., Pesonen, U., Kuikka, J. T., Kaprio, J. & Rissanen, A. (2008). Serotonin transporter binding and acquired obesity – an imaging study of monozygotic twin pairs. Physiology & Behavior 93, 724732.
Lam, D. D., Garfield, A. S., Marston, O. J., Shaw, J. & Heisler, L. K. (2010). Brain serotonin system in the coordination of food intake and body weight. Pharmacology, Biochemistry, and Behavior 97, 8491.
Lawton, C. L., Wales, J. K., Hill, A. J. & Blundell, J. E. (1995). Serotoninergic manipulation, meal-induced satiety and eating pattern: effect of fluoxetine in obese female subjects. Obesity Research 3, 345356.
Lee, R., Garcia, F., Van De Kar, L. D., Hauger, R. D. & Coccaro, E. F. (2003). Plasma oxytocin in response to pharmaco-challenge to D-fenfluramine and placebo in healthy men. Psychiatry Research 118, 129136.
Lenoir, M., Serre, F., Cantin, L. & Ahmed, S. H. (2007). Intense sweetness surpasses cocaine reward. PLoS One 2, e698.
Livak, K. J. & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402408.
Marazziti, D., Baroni, S., Giannaccini, G., Betti, L., Massimetti, G., Carmassi, C. & Catena-Dell'Osso, M. (2012). A link between oxytocin and serotonin in humans: supporting evidence from peripheral markers. European Neuropsychopharmacology 22, 578583.
Meguid, M. M., Fetissov, S. O., Varma, M., Sato, T., Zhang, L., Laviano, A. & Rossi-Fanelli, F. (2000). Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 16, 843857.
Mitra, A., Gosnell, B. A, Schioth, H. B., Grace, M. K., Klockars, A., Olszewski, P. K. & Levine, A. S. (2010). Chronic sugar intake dampens feeding-related activity of neurons synthesizing a satiety mediator, oxytocin. Peptides 31, 13461352.
Mottolese, R., Redoute, J., Costes, N., Le Bars, D. & Sirigu, A. (2014). Switching brain serotonin with oxytocin. Proceedings of the National Academy of Sciences of the United States of America 111, 86378642.
Murray, S., Tulloch, A., Gold, M. S. & Avena, N. M. (2014). Hormonal and neural mechanisms of food reward, eating behaviour and obesity. Nature Reviews Endocrinology 10, 540552.
Park, S., Harrold, J. A., Widdowson, P. S. & Williams, G. (1999). Increased binding at 5-HT(1A), 5-HT(1B), and 5-HT(2A) receptors and 5-HT transporters in diet-induced obese rats. Brain Research 847, 9097.
Paxinos, G., Watson, C. R. & Emson, P. C. (1980). AChE-stained horizontal sections of the rat brain in stereotaxic coordinates. Journal of Neuroscience Methods 3, 129149.
Quarta, D. & Smolders, I. (2014). Rewarding, reinforcing and incentive salient events involve orexigenic hypothalamic neuropeptides regulating mesolimbic dopaminergic neurotransmission. European Journal of Pharmaceutical Sciences 57, 210.
Rouch, C., Nicolaidis, S. & Orosco, M. (1999). Determination, using microdialysis, of hypothalamic serotonin variations in response to different macronutrients. Physiology & Behavior 65, 653657.
Song, Z., Levin, B. E., McArdle, J. J., Bakhos, N. & Routh, V. H. (2001). Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus. Diabetes 50, 26732681.
Stice, E., Figlewicz, D. P., Gosnell, B. A., Levine, A. S. & Pratt, W. E. (2013). The contribution of brain reward circuits to the obesity epidemic. Neuroscience and Bio-behavioral Reviews 37, 20472058.
Suzuki, K., Jayasena, C. N. & Bloom, S. R. (2012). Obesity and appetite control. Experimental Diabetes Research 2012, 824305.
Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A. & Speleman, F. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology 3, 34.
Ventura, T., Santander, J., Torres, R. & Contreras, A. M. (2014). Neurobiologic basis of craving for carbohydrates. Nutrition 30, 252256.
Vucetic, Z., Carlin, J. L., Totoki, K. & Reyes, T. M. (2012). Epigenetic dysregulation of the dopamine system in diet-induced obesity. Journal of Neurochemistry 120, 891898.
Yeghiayan, S. K., Georgelis, J. H., Maher, T. J. & Lieberman, H. R. (2004). Beneficial effects of a protein free, high carbohydrate meal on rat coping behavior and neurotransmitter levels during heat stress. Nutrition Neuroscience 7, 335340.
Yoshida, M., Takayanagi, Y., Inoue, K., Kimura, T., Young, L. J., Onaka, T. & Nishimori, K. (2009). Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. Journal of Neuroscience 29, 22592271.
Zhou, F. C., Xu, Y., Bledsoe, S, Lin, R. & Kelley, M. R. (1996). Serotonin transporter antibodies: production, characterization, and localization in the brain. Brain Research. Molecular Brain Research 43, 267278.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Genetics Research
  • ISSN: 0016-6723
  • EISSN: 1469-5073
  • URL: /core/journals/genetics-research
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed