Highlights d Consumption of sucralose combined with carbohydrates impairs insulin sensitivity d This metabolic impairment is associated with decreases in neural responses to sugar d However, sweet taste perception is unaltered d Insulin sensitivity is not altered by sucralose or carbohydrate consumption alone

Caloric restriction (CR) extends lifespan through a reduction in oxidative stress, delays the onset of morbidity and prolongs lifespan. We previously reported that long-term CR hastened clinical onset, disease progression and shortened lifespan, while transiently improving motor performance in G93A mice, a model of amyotrophic lateral sclerosis (ALS) that shows increased free radical production. To investigate the long-term CR-induced pathology in G93A mice, we assessed the mitochondrial bioenergetic efficiency and oxidative capacity (CS – citrate synthase content and activity, cytochrome c oxidase - COX activity and protein content of COX subunit- I and IV and UCP3- uncoupling protein 3), oxidative damage (MDA – malondialdehyde and PC – protein carbonyls), antioxidant enzyme capacity (Mn-SOD, Cu/Zn-SOD and catalase), inflammation (TNF-α), stress response (Hsp70) and markers of apoptosis (Bax, Bcl-2, caspase 9, cleaved caspase 9) in their skeletal muscle. At age 40 days, G93A mice were divided into two groups: Ad libitum (AL; n = 14; 7 females) or CR (n = 13; 6 females), with a diet equal to 60% of AL. COX/CS enzyme activity was lower in CR vs. AL male quadriceps (35%), despite a 2.3-fold higher COX-IV/CS protein content. UCP3 was higher in CR vs. AL females only. MnSOD and Cu/Zn-SOD were higher in CR vs. AL mice and CR vs. AL females. MDA was higher (83%) in CR vs. AL red gastrocnemius. Conversely, PC was lower in CR vs. AL red (62%) and white (30%) gastrocnemius. TNF-α was higher (52%) in CR vs. AL mice and Hsp70 was lower (62%) in CR vs. AL quadriceps. Bax was higher in CR vs. AL mice (41%) and CR vs. AL females (52%). Catalase, Bcl-2 and caspases did not differ. We conclude that CR increases lipid peroxidation, inflammation and apoptosis, while decreasing mitochondrial bioenergetic efficiency, protein oxidation and stress response in G93A mice.

Summary Post-ingestive signals related to nutrient metabolism are thought to be the primary drivers of reinforcement potency of energy sources. Here, in a series of neuroimaging and indirect calorimetry human studies, we examine the relative roles of caloric load and perceived sweetness in driving metabolic, perceptual and brain responses to sugared beverages. Whereas caloric load was manipulated using the tasteless carbohydrate maltodextrin, sweetness levels were manipulated using the non-nutritive sweetener sucralose. By formulating beverages that contain different amounts of maltodextrin+sucralose, we demonstrate a non-linear association between caloric load, metabolic response and reinforcement potency, which is driven in part by the extent to which sweetness is proportional to caloric load. In particular, we show that (1) lower calorie beverages can produce greater metabolic response and condition greater brain response and liking than higher calorie beverages and (2) when sweetness is proportional to caloric load greater metabolic responses are observed. These results demonstrate a non-linear association between caloric load and reward and describe an unanticipated role for sweet taste in regulating carbohydrate metabolism, revealing a novel mechanism by which sugar-sweetened beverages influence physiological responses to carbohydrate ingestion.

ABSTRACT:The effect of television viewing (TVV) and pubertal status of 9-to 14-y-old girls on mealtime food intake (FI) after a premeal glucose drink was determined. On four separate mornings, girls randomly received equally sweetened drinks containing Sucralose (control) or glucose (1.0 g/kg body weight) in 250 mL of water 2 h after a standardized breakfast. FI from an ad libitum pizza meal was measured 30 min later with or without TVV. Appetite was measured at 15 min intervals to lunch and postmeal. TVV at mealtime had no effect on FI, however, glucose suppressed FI more with no TVV compared with TVV (24 versus 10%, p Ͻ 0.001), primarily because of its effect in peripubertal girls (p Ͻ 0.028). In postpubertal girls (n ϭ 8), glucose reduced FI by ϳ27% in both the no TVV and TVV conditions, but in peripubertal girls (n ϭ 17), reduction in FI was 22% without TVV and only 1% while TVV. Appetite correlated with FI at 30 min only in postpubertal girls. TVV at mealtime reduced caloric compensation after consumption of the glucose drink in peripubertal, but not postpubertal, girls, with no effect on mealtime FI. (Clinical trial number NCT01025687.) (Pediatr Res 70: 513-517, 2011) F ood intake (FI) regulation in children is influenced by both physiological and environmental factors. Physiological signals of satiety and satiation are primary regulators of FI and energy balance (1). However, many nonfood-related stimuli in the mealtime environment impact this regulation (2). In children, excessive screen time (4 ϩ h/d) has been associated with increased incidence of obesity (3). Possible causes of this association are increased preference for energy dense foods and sweetened beverages (4), decreased resting metabolic rate (5), meal skipping (6), and reduced activity (7) while television viewing (TVV).Despite the strong associations found between obesity and TVV (7), few studies in children and adolescents have reported quantitative FI while TVV using a within-subject design. Although 3-to 5-y olds eat less while TVV (8), 15-to 16-y olds show no differences in FI when eating while TVV, no TVV, and listening to music (9). Only one study examined the effect of TVV on FI in 9-to 14-y-old children (10). Although TVV, boys ate 24% more at a pizza meal, indicating delayed satiation and showed diminished response to satiety signals after a glucose drink taken 30 min before the meal. Thus, mealtime TVV impaired physiologic signals leading to both satiety and satiation (10).The effect of TVV on satiety and satiation has not been reported for 9-to 14-y-old girls. Girls in this age range experience hormonal changes during puberty that may impact energy intake (11) and may use food and diet to address their negative perceptions of body image (12). Thus, our objective was to investigate the effect of TVV while eating and pubertal status on subjective appetite and mealtime FI 30 min after consumption of glucose (1.0 g/kg body weight) or noncaloric sweetened drink in 9-to 14-y-old girls. Our hypothesis was that TVV reduces the effect of...

The effect of short duration exercise (EXR) on food intake (FI) and energy balance (EB) is not well understood in either normal weight (NW) or overweight (OW) and obese (OB) 9-14 years old children. Our purpose was to describe the effects of activity and a glucose drink on short term FI, appetite, and EB in NW, OW, and OB boys. Each boy received in random order either a noncaloric Sucralose sweetened control or glucose (1.0 g·kg(-1) body weight) drink 5 min after either exercise (EXR) or sedentary (SED) activity. Boys exercised for 15 min at their ventilation threshold (V(T)) in experiment 1 or at 25% above their V(T) in experiment 2. FI was measured at an ad libitum pizza meal 30 min after drink consumption. FI was lower after the glucose drink (p < 0.001) but not affected by activity, even though EXR increased appetite (p < 0.001). OW/OB boys ate more total food than NW boys (p = 0.020). EB over the duration of the experiments was reduced by EXR in OW/OB boys (p = 0.013) but not in NW boys in either experiment (p > 0.05). We conclude that intake regulation in OW/OB boys in response to a glucose drink is similar to NW boys, but it may be less responsive to activity.

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