Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats
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Animal Industry Report Animal Industry Report AS 652 ASL R2081 2006 Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats Michelle Bohan Iowa State University Lloyd L. Anderson Iowa State University Allen H. Trenkle Iowa State University Donald C. Beitz Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/ans_air Part of the Agriculture Commons, and the Animal Sciences Commons Recommended Citation Bohan, Michelle; Anderson, Lloyd L.; Trenkle, Allen H.; and Beitz, Donald C. (2006) "Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats ," Animal Industry Report: AS 652, ASL R2081. DOI: https://doi.org/10.31274/ans_air-180814-908 Available at: https://lib.dr.iastate.edu/ans_air/vol652/iss1/22 This Companion Animal is brought to you for free and open access by the Animal Science Research Reports at Iowa State University Digital Repository. It has been accepted for inclusion in Animal Industry Report by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Iowa State University Animal Industry Report 2006 Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats A.S. Leaflet R2081 ghrelin. Ghrelin is an antagonist of leptin by acting upon the neuropeptide Y/Y1 receptor pathway. Leptin causes Michelle Bohan, graduate student of biochemistry; satiety, whereas ghrelin stimulates nutrient intake. Leptin Lloyd Anderson, distinguished professor of animal science; and ghrelin thereby regulate the action of each other. Allen Trenkle, distinguished professor of animal science; Ghrelin is synthesized in the arcuate nuclei and oxyntic Donald Beitz, distinguished professor of animal science glands of the stomach. Stomach ghrelin is thought to be and biochemistry involved in physiological effects and possibly in stimulating the secretion of growth hormone. Some of the Summary and Implications physiological effects of ghrelin are hyperglycemia in Investigating the role of appetite-related hormones on humans, adiposity in rodents, increased gastric acid energy balance and body composition when varying diets secretion in rats, and increased gastric motility in rats. are consumed could provide insight into the etiology of Oxyntomodulin (OXM) is cleaved from the proglucagon obesity. Fifty-three adult male Sprague Dawley and 30 hormone, which is synthesized in the oxyntic glands of the adult male Zucker Fatty rats were assigned randomly to one stomach. Oxyntomodulin decreases food intake and of five diets: Control, 75% control, American Heart suppresses appetite in humans. Studies have been Association (AHA), Atkins, or high fat (HF). Diets were conducted to investigate the effects of OXM or ghrelin on fed for five weeks. Weekly plasma samples were collected feed intake and appetite. In this proposed study, the effects and analyzed for ghrelin, leptin, insulin, and adiponectin. of diet composition on ghrelin and OXM concentrations in Terminal plasma samples were analyzed for ghrelin, leptin, plasma of rats will be analyzed. insulin, glucagon, oxyntomodulin, adiponectin, and blood Few studies have shown the effects of diet composition metabolites. Our results indicate that macronutrient on circulating ghrelin concentration with respect to obesity. composition of the diet influences appetite-related hormones Most studies have involved ghrelin and its effects on differently in genetically divergent rats. For example, healthy humans or humans with specific disease states such glucagon concentration was higher in obese rats fed the as anorexia nervosa (AN), polycystic ovary syndrome, and Atkins diet in comparison to obese rats fed the HF and 75% chronic heart failure or surgical modifications of the control diets (P<0.05) and tended to be higher in obese rats stomach. Patients with AN have higher plasma ghrelin fed the Atkins diet in comparison with rats fed the AHA and concentrations than do normal humans. Furthermore, control diets (0.06<P<0.15). In lean rats, glucagon plasma ghrelin in AN patients is associated negatively with concentration was higher in rats fed the Control diet in body mass index (BMI) values. Patients with chronic heart comparison with all other diets (P<0.03). Influence of diet failure and cachexia have high plasma ghrelin and animal type on other related hormones will be concentrations. Ghrelin administered to patients with presented. Our results document a relationship of appetite- chronic heart failure improves hemodynamic function. related hormones with respect to diet composition in lean Ghrelin could serve two roles in chronic heart failure: and obese rats as a model for humans. creating a positive energy balance and improving hemodynamic function in the patients. There have been a Introduction number of studies conducted with obese humans and the Ghrelin is a newly discovered hormone that acts upon effects of gastric bypass surgery on plasma ghrelin the growth hormone secretagogue receptor (GSH-R). The concentrations. Patients who had gastric bypass surgery GSH-R was discovered in 1997. Many synthetic have lower plasma ghrelin concentrations. Lower plasma compounds act upon this receptor to change the animal’s ghrelin concentrations in gastric bypass patients could be body composition. Since the discovery of the GSH-R, the explained by the surgery. Because ghrelin is produced search for an endogenous ligand has been conducted. In primarily in the stomach, gastric bypass may have an effect 1999, ghrelin was discovered to be an endogenous ligand of on the ghrelin-producing cells in the fundus of the stomach. this receptor. This observation would explain the long-term weight loss Since the discovery and isolation of ghrelin, many with gastric bypass surgery. studies have been performed to determine the function of In 2002, Beck and colleagues showed that rats fed a ghrelin in the body. Ghrelin stimulates growth hormone high carbohydrate diet had higher plasma ghrelin than did release independent of the growth hormone releasing rats fed a low carbohydrate diet. This study was a long- hormone. Additionally, leptin activity is controlled by term feeding study and demonstrated the long-term effects of diet on ghrelin concentration. In a study by Monteleone and colleagues in 2003, healthy non-obese women were fed either a high fat or high carbohydrate meal. The high NPY, AgRP, carbohydrate meal caused the greatest increase in plasma MCH ghrelin. Also, hunger sensation of subjects fed the high Pancreas carbohydrate diet was suppressed more than that of subjects Brain fed the high fat diet. Ghrelin concentration, however, increased with weight loss of humans when eating a low fat, OXM Ghrelin POMC, high carbohydrate diet. Diet-induced obesity, however, was GLP-1 CART, CRH Insulin not related directly to ghrelin concentration in juvenile rats Stomach Glucagon prone to obesity. In 2003, Weigle and colleagues showed that high fat diets decrease adiposity without increasing appetite. The few studies involving ghrelin and diet GLP-1 Leptin PYY Small and Large composition have conflicting results, leaving the Intestines relationship between ghrelin and diet composition unclear. PYY Adipose Despite a number of studies of plasma ghrelin and its effects on obesity, the mechanism by which ghrelin causes Suppressors of feed intake in red adiposity remains unknown. Plasma ghrelin concentrations Activators of feed intake in blue in obese humans are lower than those of normal weight individuals. Cerebrospinal fluid (CSF) ghrelin is lower in Figure 1 Regulation of food intake and body obese humans than in normal weight humans. Obese composition humans have lower ghrelin concentrations both in plasma Suppressors of feed intake are CART, CRH, GLP-1, and CSF. This latter observation is contrary to the findings Leptin, OXM, POMC, and PYY. in rodents where ghrelin was injected subcutaneously and an Activators of feed intake are Ghrelin, AgRP, MCH, and increase in adiposity was shown. In 2002, English and NPY. colleagues demonstrated that refeeding after fasting did not Abbreviations: decrease the ghrelin concentrations in obese human patients. NPY = Neuropeptide Y In normal weight humans, fasting ghrelin concentrations AgRP = Agouti-related protein decreased after feeding. In 2004, Salbe et al. showed that MCH = Melanin-concentrating hormone ghrelin has a negative association with ad libitum feed POMC = Pro-opiomelanocortin intake. Salbe and colleagues, however, measured fasting CART = Cocaine- and amphetamine-regulated (average) ghrelin as their measurement, which may not be transcript representative of the rise in ghrelin concentration before a CRH = Corticotropin-releasing hormone meal. Furthermore, many studies such as the Salbe study PYY = Peptide YY used a total ghrelin assay rather than the active ghrelin GLP-1 = Glucagon-like peptide 1 assay. This finding may explain the disparity in the OXM = Oxyntomodulin literature about the relationship of ghrelin, diet composition, and obesity. Studying the effects of diet composition on The objective of this study is to investigate the effect of ghrelin concentrations in both normal and obese patients is macronutrients on ghrelin concentration and expression, necessary to fully understand the mechanisms by which the concentration of other hormones that regulated feed intake, body controls feed intake and body composition.