Recent studies have demonstrated that consuming high fructose corn syrup (HFCS)- or sucrose-sweetened beverages increase lipid/lipoprotein risk factors for cardiovascular disease (CVD) in healthy adults compared with iso-caloric amounts of glucose or low-fat milk. The longest of these studies, which utilized a 6-month intervention, also showed increased liver and muscle TG and increased visceral adipose deposition. Neither of these studies found differences in weight gain between subjects consuming HFCS/sucrose beverages compared with control beverages. These results suggest that it is not just excess calories and weight gain that mediates the effects of dietary sugar on the development of metabolic disease, but rather dietary sugar appears to be an independent contributor. However, it is not known whether consumption of excessive amounts of sugar can increase risk factors for metabolic disease in the absence of positive energy balance and weight gain, nor whether the adverse effects of sugar consumption are exacerbated by weight gain. This study will compare the contribution of sugar with the contribution of energy level to the increases in risk factors for metabolic disease induced by consumption of HFCS-sweetened beverages under energy-balanced or ad libitum conditions. We will measure risk factors and processes associated with metabolic disease in 4 groups of young, healthy adults who will consume 1) 25% of energy requirement (Ereq) as HFCS-sweetened beverages with an energy-balanced diet, 2) aspartame-sweetened beverages with an energy-balanced diet, 3) 25% Ereq as HFCS-sweetened beverages with an ad libitum diet, or 4) aspartame-sweetened beverages with an ad libitum diet for 8 weeks. All diets, formulated to achieve a comparable macronutrient intake (55% Ereq as carbohydrate, 35% fat, 15% protein) among all 4 experimental groups, will be provided to the subjects. We hypothesize that under energy balanced conditions that prevent body weight gain, consumption of HFCS-sweetened beverages will result in adverse metabolic effects compared with aspartame-sweetened beverages. Consumption of HFCS-sweetened beverages with the ad libitum diet will result in increased energy intake and body weight gain compared with aspartame-sweetened beverages, and will also result in adverse metabolic effects that are more marked than with consumption of HFCS-sweetened beverages with the energy-balanced diet. These results will demonstrate that consumption of HFCS-sweetened beverages increases risk for metabolic disease both directly, via the adverse effects of fructose on lipid and carbohydrate metabolism, and indirectly, via the effects of HFCS-sweetened beverages to promote excess energy intake and body weight gain. These findings will have the potential to influence dietary guidelines and public health policy.

Public Health Relevance

It is not known whether consumption of excessive amounts of sugar can increase risk factors for cardiovascular disease or diabetes in the absence of increased food (caloric) intake and weight gain, nor whether the negative effects of sugar consumption are made worse when accompanied by weight gain. This project will investigate the effects of excess sugar when consumed with an energy-balanced diet that prevents weight gain, and compare these effects to when excess sugar is consumed with a diet that can cause weight gain. The results will determine whether excess sugar consumption and excess caloric intake that lead to weight gain have independent and additive effects on risk factors for cardiovascular disease or diabetes, and will have the potential to influence dietary guidelines and public health policy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
3R01HL121324-05S1
Application #
9888232
Study Section
Program Officer
Redmond, Nicole
Project Start
2019-06-01
Project End
2020-05-31
Budget Start
2019-07-19
Budget End
2020-05-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Davis
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Seelke, Adele M; Rhine, Maya A; Khun, Konterri et al. (2018) Intranasal oxytocin reduces weight gain in diet-induced obese prairie voles. Physiol Behav 196:67-77
Acevedo, Claire; Sylvia, Meghan; Schaible, Eric et al. (2018) Contributions of Material Properties and Structure to Increased Bone Fragility for a Given Bone Mass in the UCD-T2DM Rat Model of Type 2 Diabetes. J Bone Miner Res 33:1066-1075
Hsu, Ming-Fo; Bettaieb, Ahmed; Ito, Yoshihiro et al. (2017) Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria. Sci Rep 7:461
Green, Adrian J; Graham, James L; Gonzalez, Eduardo A et al. (2017) Perinatal triphenyl phosphate exposure accelerates type 2 diabetes onset and increases adipose accumulation in UCD-type 2 diabetes mellitus rats. Reprod Toxicol 68:119-129
Bettaieb, Ahmed; Koike, Shinichiro; Chahed, Samah et al. (2017) Podocyte-specific soluble epoxide hydrolase deficiency in mice attenuates acute kidney injury. FEBS J 284:1970-1986
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
Piccolo, Brian D; Graham, James L; Stanhope, Kimber L et al. (2016) Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model. Am J Physiol Endocrinol Metab 310:E958-69