Metabolic effects of intermittent access to caloric or non-caloric sweetened solutions in mice fed a high-caloric diet

- Sucrose, HFCS and maltodextrin solutions induce body weight gain in HFHS-fed mice.
- Intake of these solutions leads to liver lipid accumulation.
- Sucrose and fructose solutions induce a higher fat mass and glucose intolerance.
- Sucrose and fructose solutions modulate central hypothalamic signaling.
- Intake of a sucrose solution modulates central reward signaling.

Human consumption of obesogenic diets and soft drinks, sweetened with different molecules, is increasing worldwide, and increases the risk of metabolic diseases. We hypothesized that the chronic consumption of caloric (sucrose, high-fructose corn syrup (HFCS), maltodextrin) and non-caloric (sucralose) solutions under 2-hour intermittent access, alongside the consumption of a high-fat high-sucrose diet, would result in differential obesity-associated metabolic abnormalities in mice.Male C57BL/6 mice had ad libitum access to an HFHS diet and to water (water control group). In addition, some mice had access, 2 h/day, 5 days/week (randomly chosen) for 12 weeks, to different solutions: i) a sucrose solution (2.1 kJ/ml), ii) an HFCS solution (2.1 kJ/ml), iii) a maltodextrin solution (2.1 kJ/ml) and a sucralose solution (60 mM) (n = 15/group).Despite no changes in total caloric intake, 2 h-intermittent access to the sucrose, HFCS or maltodextrin solutions led to increased body weight and accumulation of lipids in the liver when compared to the group consuming water only. The HFCS and sucrose solutions induced a higher fat mass in various fat depots, glucose intolerance, increased glucose oxidation at the expense of lipid oxidation, and a lower hypothalamic expression of NPY in the fasted state. HFCS also reduced proopiomelanocortin expression in the hypothalamus. 2 h-intermittent access to sucralose did not result in significant changes in body composition, but caused a stronger expression of CART in the hypothalamus. Finally, sucrose intake showed a trend to increase the expression of various receptors in the nucleus accumbens, linked to dopamine, opioid and endocannabinoid signaling.In conclusion, 2 h-intermittent access to caloric solutions (especially those sweetened with sucrose and HFCS), but not sucralose, resulted in adverse metabolic consequences in high-fat high-sucrose-fed mice.