Overnight Access to Sugar Solutions Affects mRNA Expression of Several Neuropeptides in Different Hypothalamic Regions in Rats

Changhui Zhao¹, Eric S. Campbell¹, Anna E. Tschiffely¹ and Thomas W. Castonguay^1,

¹Department of Nutrition and Food Science, University of Maryland, College Park

Cite this paper:
Changhui Zhao, Eric S. Campbell, Anna E. Tschiffely and Thomas W. Castonguay. Overnight Access to Sugar Solutions Affects mRNA Expression of Several Neuropeptides in Different Hypothalamic Regions in Rats. Journal of Food and Nutrition Research. 2015; 3(1):69-76. doi: 10.12691/jfnr-3-1-12

Abstract

It has been known for years that free access to sugar solutions can cause weight gain and/or obesity in rats. We recently reported that brief access to sugar solutions can affect the hypothalamic neuropeptides that help to regulate energy balance. In this paper, we present the results in which we examined the effects of these sugars on the expression of several neuropeptides within specific hypothalamic regions. We provided Sprague Dawley rats 24 h access to 15% solutions of glucose, fructose, sucrose or high fructose corn syrup (HFCS) and then dissected portions of the paraventricular hypothalamic nuclei (PVN), the ventromedial hypothalamus (VMH) and the lateral hypothalamus (LH). We then evaluated the expression of several neuropeptides in these tissues, all of which were previously shown to be influenced by free access to sugar solutions using PCR array. Of the four sugar solutions tested, only fructose decreased expression of cholecystokinin (CCK) significantly, and only in the PVN. Glucose and sucrose significantly increased the expression of Tumor Necrosis Factor α (TNF-α) only in the PVN. Fructose and sucrose decreased Growth Hormone (GH) in the VMH. Further analysis indicated that it was fructose intake that was negatively correlated with both CCK and GH expression. Rats that had access to sugar solutions consumed less chow but maintained control levels of total caloric intake. We conclude that 24 h free access to different sugars can influence the expression of several hypothalamic neuropeptides in different ways. Changes in the expression of these neuropeptides do not disrupt total daily energy intake immediately but may nevertheless contribute to the obesity caused by long term access to sugar solutions.

Keywords:
fructose HFCS glucose sucrose energy regulation

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References:

[1]	Castonguay TW, Hirsch E, Collier G. Palatability of sugar solutions and dietary selection? Physiology & Behavior 1981; 27: 7-12.
[2]	Kanarek RB, Orthen-Gambill N. Differential effects of sucrose, fructose and glucose on carbohydrate-induced obesity in rats. The Journal of nutrition 1982; 112: 1546-54.
[3]	Bocarsly ME, Powell ES, Avena NM, Hoebel BG. High-fructose corn syrup causes characteristics of obesity in rats: Increased body weight, body fat and triglyceride levels. Pharmacology Biochemistry and Behavior 2010; 97: 101-6.
[4]	Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000; 404: 661-71.
[5]	Campbell ES, Castonguay TW. Fructose intake and circulating triglycerides: an examination of the roles of APOC 3 and FOXO1. The FASEB Journal 2013; 27: 1074.8.
[6]	London E, Castonguay TW. High Fructose Diets Increase 11β‐Hydroxysteroid Dehydrogenase Type 1 in Liver and Visceral Adipose in Rats Within 24‐h Exposure. Obesity 2011; 19: 925-32.
[7]	Masuzaki H, Flier J. Tissue-specific glucocorticoid reactivating enzyme, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1)--a promising drug target for the treatment of metabolic syndrome. Current drug targets. Immune, endocrine and metabolic disorders 2003; 3: 255-62.
[8]	Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001; 294: 2166-70.
[9]	Page KA, Chan O, Arora J, Belfort-DeAguiar R, Dzuira J, Roehmholdt B, Cline GW, Naik S, Sinha R, Constable RT. Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward PathwaysFructose Consumption and Weight Gain. JAMA 2013; 309: 63-70.
[10]	Stellar E. The physiology of motivation. Psychological review 1954; 61: 5.
[11]	Weingarten HP, Chang P, McDonald T. Comparison of the metabolic and behavioral disturbances following paraventricular-and ventromedial-hypothalamic lesions. Brain research bulletin 1985; 14: 551-9.
[12]	Colley DL, Castonguay TW. Effects of sugar solutions on hypothalamic appetite regulation (in press). Physiology & Behavior 2014.
[13]	Clément-Ziza M, Munnich A, Lyonnet S, Jaubert F, Besmond C. Stabilization of RNA during laser capture microdissection by performing experiments under argon atmosphere or using ethanol as a solvent in staining solutions. Rna 2008;14:2698-704.
[14]	Lindqvist A, Baelemans A, Erlanson-Albertsson C. Effects of sucrose, glucose and fructose on peripheral and central appetite signals. Regulatory Peptides 2008; 150: 26-32.
[15]	Ventura EE, Davis JN, Goran MI. Sugar content of popular sweetened beverages based on objective laboratory analysis: focus on fructose content. Obesity 2011; 19: 868-74.
[16]	Walker RW, Dumke KA, Goran MI. Fructose content in popular beverages made with and without high-fructose corn syrup. Nutrition 2014; 30: 928-35.
[17]	Kraly FS, Carty WJ, Resnick S, Smith GP. Effect of cholecystokinin on meal size and intermeal interval in the sham-feeding rat. Journal of comparative and physiological psychology 1978; 92: 697.
[18]	Schwartz GJ, Whitney A, Skoglund C, Castonguay TW, Moran TH. Decreased responsiveness to dietary fat in Otsuka Long-Evans Tokushima fatty rats lacking CCK-A receptors. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 1999; 277: R1144-R51.
[19]	Chen H, Kent S, Morris MJ. Is the CCK2 receptor essential for normal regulation of body weight and adiposity? European Journal of Neuroscience 2006; 24: 1427-33.
[20]	Weiland TJ, Voudouris NJ, Kent S. The role of CCK2 receptors in energy homeostasis: insights from the CCK2 receptor-deficient mouse. Physiology & Behavior 2004; 82: 471-6.
[21]	Chen J, Scott KA, Zhao Z, Moran TH, Bi S. Characterization of the feeding inhibition and neural activation produced by dorsomedial hypothalamic cholecystokinin administration. Neuroscience 2008; 152: 178-88.
[22]	Zhu G, Yan J, Smith WW, Moran TH, Bi S. Roles of dorsomedial hypothalamic cholecystokinin signaling in the controls of meal patterns and glucose homeostasis. Physiology & Behavior 2012; 105: 234-41.
[23]	Tebbe J, Mönnikes H, Pluntke K, Bauer C, Arnold R. Cholecystokinin (CCK) microinfused into the paraventricular nucleus of the hypothalamus (PVN) inhibits gastric emptying and stimulates colonic motor activity in the conscious rat. Gastroenterology 1998; 114: A1184-A5.
[24]	Abramov A, Kolesnik YM, Trzhetsinskii S, Orlovskii nM. Changes in the cholecystokinin-synthesizing system of the hypothalamus in experimental diabetes mellitus in rats. Neuroscience and behavioral physiology 1999; 29: 621-4.
[25]	De Fanti BA, Backus RC, Hamilton JS, Gietzen DW, Horwitz BA. Lean (Fa/Fa) but not obese (fa/fa) Zucker rats release cholecystokinin at PVN after a gavaged meal. American Journal of Physiology-Endocrinology and Metabolism 1998; 275: E1-E5.
[26]	Mahony S, Tisdale M. Induction of weight loss and metabolic alterations by human recombinant tumour necrosis factor. British journal of cancer 1988; 58: 345.
[27]	Romanatto T, Cesquini M, Amaral ME, Roman ÉA, Moraes JC, Torsoni MA, Cruz-Neto AP, Velloso LA. TNF-α acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient—effects on leptin and insulin signaling pathways. Peptides 2007; 28: 1050-8.
[28]	De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, Boschero AC, Saad MJ, Velloso LcA. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 2005; 146: 4192-9.
[29]	Swaroop JJ, Rajarajeswari D, Naidu J. Association of TNF-α with insulin resistance in type 2 diabetes mellitus. The Indian journal of medical research 2012;135:127.
[30]	Wang X, Ge A, Cheng M, Guo F, Zhao M, Zhou X, Liu L, Yang N. Increased hypothalamic inflammation associated with the susceptibility to obesity in rats exposed to high-fat diet. Experimental diabetes research 2012; 2012.
[31]	Jørgensen JOL, Pedersen SB, Børglum J, Møller N, Schmitz O, Christiansen JS, Richelsen B. Fuel metabolism, energy expenditure, and thyroid function in growth hormone-treated obese women: A double-blind placebo-controlled study. Metabolism 1994; 43: 872-7.
[32]	Sakharova AA, Horowitz JF, Surya S, Goldenberg N, Harber MP, Symons K, Barkan A. Role of growth hormone in regulating lipolysis, proteolysis, and hepatic glucose production during fasting. The Journal of Clinical Endocrinology & Metabolism 2008; 93: 2755-9.
[33]	Gahete MD, Córdoba-Chacón J, Luque RM, Kineman RD. The rise in growth hormone during starvation does not serve to maintain glucose levels or lean mass but is required for appropriate adipose tissue response in female mice. Endocrinology 2012; 154: 263-9.
[34]	Rosen T, Bosaeus I, TöIli J, Lindstedt G, Bengtsson B-Å. Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency. Clinical Endocrinology 1993; 38: 63-71.
[35]	Coxam V, Davicco M-J, Barlet J-P. Effect of triglycerides on growth hormone (GH)-releasing factor-mediated GH secretion in newborn calves. Domestic animal endocrinology 1989; 6: 389-93.
[36]	Lutz TA. Control of energy homeostasis by amylin. Cellular and molecular life sciences 2012; 69: 1947-65.
[37]	Schuhler S, Warner A, Finney N, Bennett G, Ebling F, Brameld J. Thyrotrophin-Releasing Hormone Decreases Feeding and Increases Body Temperature, Activity and Oxygen Consumption in Siberian Hamsters. Journal of neuroendocrinology 2007; 19: 239-49.
[38]	Fekete C, Légrádi G, Mihály E, Huang Q-H, Tatro JB, Rand WM, Emerson CH, Lechan RM. α-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. The Journal of Neuroscience 2000; 20: 1550-8.
[39]	Rumessen JJ. Fructose and related food carbohydrates: sources, intake, absorption, and clinical implications. Scandinavian journal of gastroenterology 1992; 27: 819-28.
[40]	Bray G, Popkin B. Calorie‐sweetened beverages and fructose: what have we learned 10 years later. Pediatric obesity 2013; 8: 242-8.