Effects of three intense sweeteners on fat storage in the C. elegans model Jolene Zheng a,b,⇑ , Frank L. Greenway b , Steven B. Heymsfield b , William D. Johnson b , Jason F. King c , Michael J. King c , Chenfei Gao a , Yi-Fang Chu d , John W. Finley a a Department of Food Science, Louisiana State University Agricultural Center, Baton Rouge, LA 70803, United States b Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, United States c Louisiana State University, Baton Rouge, LA 70803, United States d PepsiCo Global R&D, Barrington, IL 60010, United States article info Article history: Received 26 March 2013 Received in revised form 15 January 2014 Accepted 28 February 2014 Available online 13 March 2014 Keywords: Intense sweetener Lipids Metabolism Insulin sensitivity abstract Beverages sweetened with caloric sweeteners (CS), glucose, sucrose or high-fructose corn syrup, are asso- ciated with weight gain. Beverages sweetened with intense sweeteners (IS) are marketed as low-calorie substitutes to prevent beverages-associated weight gain. Using Caenorhabditis elegans, the effects on intestinal fat deposition (IFD) and pharyngeal pumping rate (PPR) of cola beverages sweetened with glu- cose, aspartame, or aspartame plus acesulfame-potassium (AceK) were compared. Control groups received Escherichia coli (OP50) only. Study I: the nematodes received additional glucose- or IS-sweetened beverages. Study II: the nematodes received additional glucose, aspartame, or aspartame plus AceK (AAK). Beverages containing CS or IS (aspartame or AAK) did not alter IFD in wild type (N2) or in daf- 16 deficiency. The CS cola increased IFD in sir-2.1 deficiency (P < 0.05). The AAK-cola increased IFD in daf-16/daf-2 deficiency and sir-2.1 deficiency (P < 0.05). Glucose increased IFD in N2 and daf-16 deficiency (P < 0.05). Aspartame showed a tendency towards reduced IFD in N2 and decreased IFD in daf-16/daf-2 deficiency (P < 0.05). AAK increased IFD in daf-16 deficiency and sir-2.1 deficiency (P < 0.05), and reversed the aspartame-induced reduction in IFD. The aspartame-sweetened cola increased the PPR in daf-16/daf-2 deficiency and daf-16 deficiency (P < 0.05); similar results were obtained in N2 with both IS (P < 0.05). AAK increased the PPR in daf-16/daf-2, daf-16, and sir-2.1 deficiencies (P < 0.05). Thus, IS increased the PPR, a surrogate marker of lifespan. Aspartame may have an independent effect in reducing IFD to assist humans desiring weight loss. AceK may increase IFD in presence of insulin resistance. Ó 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The majority of Americans are either overweight or obese. Only limited medications are available to treat obesity which costs the US health care system more than $100 billion a year, and the pre- disposition of obese patients to develop diabetes and its associated complications generates even higher costs. The mainstays of weight management have been dietary restriction, exercise, and behavior modification programs. When such a life-style program was combined with meal replacements, adults lost an average of 22.6 to 25.5 ± 1% of their body weight, but after 3 years only half of the participants were able to maintain weight losses of 5% of their initial body weight [27]. In fact, medications for the treatment of obesity have historically had a poor track record of safety and many have been removed from the market. Obesity surgery gives sustainable weight loss, but it is expensive and carries the risks associated with any major surgery. Excessive caloric intake is one of the most important factors contributing to obesity and a safe food that contributes to limited body fat gain would be highly desirable. Non-caloric sweeteners can replace calories from sugar, particularly in beverages. Both the American Heart Association and the American Diabetes Associ- ation have recommended the use of artificially sweetened bever- ages as a dietary intervention to reduce caloric intake. A sweet taste plays a role in the anticipatory function that induces the ce- phalic phase of eating, a phase that evokes sequential pre-absorp- tive and post-ingestive physiological regulations potentiating caloric intake [20]. In humans, non-nutritive sweetened liquids do not induce the cephalic phase of insulin release (CPIR) or the http://dx.doi.org/10.1016/j.cbi.2014.02.016 0009-2797/Ó 2014 Elsevier Ireland Ltd. All rights reserved. Abbreviations: AceK, acesulfame-potassium; AAK, aspartame plus AceK; CS, caloric sweeteners; IS, intense sweeteners; IFD, intestinal fat deposition; PPR, pharyngeal pumping rate. ⇑ Corresponding author at: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, United States. Tel./fax: +1 (225) 763 2847. E-mail address: zhengz@lsu.edu (J. Zheng). Chemico-Biological Interactions 215 (2014) 1–6 Contents lists available at ScienceDirect Chemico-Biological Interactions journal homepage: www.elsevier.com/locate/chembioint