The parent study for this proposed ancillary study is an NIH/NHLBI-funded investigation comparing the effects of consuming sweetened beverages for 2 weeks in young (18-40 years), normal weight and overweight/obese adults (5R01HL091333-02: Effects of 2wk fructose &HFCS consumption on lipid dysregulation &insulin resistance). Baseline experimental procedures (including 24-h serial blood sampling) are conducted while subjects reside as inpatients at the CTSC-funded Clinical Research Center (CCRC) for 3.5 days and consume an energy-balanced, high complex carbohydrate diet. Subjects then consume sweetened beverages providing 25% of energy requirements as fructose, glucose, or high fructose corn syrup (HFCS);or 0, 10, or 17.5% of energy as fructose or HFCS along with their usual ad libitum diet. At the end of the 2-week intervention, subjects return to the CCRC and the same experimental procedures are performed while subjects consume an energy-balanced diet, which includes the assigned sweetened beverages. The early results from this investigation indicate that consumption of HFCS-sweetened beverages at 25% of energy results in significant increases of late-night postprandial triglyceride (TG) concentrations, and of fasting LDL cholesterol and apolipoprotein-B (ApoB) concentrations that are comparable in magnitude to those observed after consumption of beverages sweetened with 100% fructose. Consumption of glucose-sweetened beverages does not alter these parameters. There is considerable evidence to support the hypothesis that postprandial hypertriglyceridemia is a key metabolic disturbance that gives rise to the lipid dysregulation characteristic of metabolic syndrome and type 2 diabetes. The purpose of this proposal is to investigate the mechanisms that contribute to the postprandial hypertriglyceridemia induced by fructose and HFCS consumption by quantifying the absolute and proportional contributions of fatty acids derived from de novo lipogenesis (DNL), diet, and free fatty acids (FFA) from adipose TG lipolysis to fasting and postprandial levels of triglyceride-rich lipoproteins (TRL). Stable isotopes will be administered (via oral consumption and 26-h intravenous infusions) to subsets of subjects during the 24-h serial blood sampling protocols that are conducted in all study participants during consumption of energy-balanced, high complex carbohydrate meals at baseline, and meals consumed with beverages sweetened with HFCS, fructose, glucose or aspartame at the end of intervention. The specific objective of these studies is to test the hypothesis that 2 weeks of fructose or HFCS consumption will increase the absolute and proportional contributions of fatty acids derived from DNL to late-night increases of TRL, and that the increases of DNL-fatty acid will be a critical determinant of the increases of fasting LDL and ApoB concentrations. A second objective is to determine the doses of HFCS that increase the absolute and proportional contributions of DNL-fatty acids to postprandial TRL.

Public Health Relevance

There is evidence to suggest that consumption of high sugar diets is associated with increased incidence of cardiovascular disease and diabetes, and the early results from the parent study indicate that consumption of beverages sweetened with high fructose corn syrup (HFCS) at 25% of energy requirement for 2 weeks increases risk factors for cardiovascular disease, including late-night triglyceride (TG) concentrations, and fasting LDL-cholesterol and apolipoprotein-B concentrations. Scientific evidence suggests that increased plasma TG concentrations after meals lead to the increases of other risk factors, and studies are proposed to mechanistically investigate the late-night postprandial increase of TG induced by consumption of HFCS and fructose. These studies will help to determine how sugar consumption may promote increased risk for cardiovascular and related metabolic diseases. (End of Abstract)

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-G (M1))
Program Officer
Ershow, Abby
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Davis
Veterinary Sciences
Schools of Veterinary Medicine
United States
Zip Code
Stevens, Joseph R; Kearney, Monica L; St-Onge, Marie-Pierre et al. (2016) Inverse association between carbohydrate consumption and plasma adropin concentrations in humans. Obesity (Silver Spring) 24:1731-40
Stanhope, Kimber L (2016) Sugar consumption, metabolic disease and obesity: The state of the controversy. Crit Rev Clin Lab Sci 53:52-67
Green, Adrian J; Graham, James L; Gonzalez, Eduardo A et al. (2016) Perinatal triphenyl phosphate exposure accelerates type 2 diabetes onset and increases adipose accumulation in UCD-type 2 diabetes mellitus rats. Reprod Toxicol :
Tryon, Matthew S; Stanhope, Kimber L; Epel, Elissa S et al. (2015) Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain and Body. J Clin Endocrinol Metab 100:2239-47
Stanhope, Kimber L; Medici, Valentina; Bremer, Andrew A et al. (2015) A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults. Am J Clin Nutr 101:1144-54
Blevins, James E; Graham, James L; Morton, Gregory J et al. (2015) Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys. Am J Physiol Regul Integr Comp Physiol 308:R431-8
Butler, Andrew A; St-Onge, Marie-Pierre; Siebert, Emily A et al. (2015) Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans. Sci Rep 5:14691
Buss, Julia; Havel, Peter J; Epel, Elissa et al. (2014) Associations of ghrelin with eating behaviors, stress, metabolic factors, and telomere length among overweight and obese women: preliminary evidence of attenuated ghrelin effects in obesity? Appetite 76:84-94
Bremer, Andrew A; Stanhope, Kimber L; Graham, James L et al. (2014) Fish oil supplementation ameliorates fructose-induced hypertriglyceridemia and insulin resistance in adult male rhesus macaques. J Nutr 144:5-11
Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L et al. (2014) Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats. J Endocrinol 221:133-44

Showing the most recent 10 out of 28 publications