Barkha P. Patel

Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS.

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.

Comparison of Total Protein Concentration in Skeletal Muscle as Measured by the Bradford and Lowry Assays

The Lowry and Bradford assays are the most commonly used methods of total protein quantification, yet vary in several aspects. To date, no comparisons have been made in skeletal muscle. We compared total protein concentrations of mouse red and white gastrocnemius, reagent stability, protein stability and range of linearity using both assays. The Lowry averaged protein concentrations 15% higher than the Bradford with a moderate correlation (r = 0.36, P = 0.01). However, Bland-Altman analysis revealed considerable bias (15.8 +/- 29.7%). Both Lowry reagents and its protein-reagent interactions were less stable over time than the Bradford. The linear range of concentration was smaller for the Lowry (0.05-0.50 mg/ml) than the Bradford (0-2.0 mg/ml). We conclude that the Bradford and Lowry measures of total protein concentration in skeletal muscle are not interchangeable. The Bradford and Lowry assays have various strengths and weaknesses in terms of substance interference and protein size. However, the Bradford provides greater reagent stability, protein-reagent stability and range of linearity, and requires less time to analyse compared to the Lowry assay.

Nutritional and exercise-based interventions in the treatment of amyotrophic lateral sclerosis

BACKGROUND & AIMS Disease pathogenesis in amyotrophic lateral sclerosis (ALS) involves a number of interconnected mechanisms all resulting in the rapid deterioration of motor neurons. The main mechanisms include enhanced free radical production, protein misfolding, aberrant protein aggregation, excitotoxicity, mitochondrial dysfunction, neuroinflammation and apoptosis. The aim of this review is to assess the efficacy of using nutrition- and exercise-related interventions to improve disease outcomes in ALS. METHODS Studies involving nutrition or exercise in human and animal models of ALS were reviewed. RESULTS Treatments conducted in animal models of ALS have not consistently translated into beneficial results in clinical trials due to poor design, lack of power and short study duration, as well as differences in the genetic backgrounds, treatment dosages and disease pathology between animals and humans. However, vitamin E, folic acid, alpha lipoic acid, lyophilized red wine, coenzyme Q10, epigallocatechin gallate, Ginkgo biloba, melatonin, Cu chelators, and regular low and moderate intensity exercise, as well as treatments with catalase and l-carnitine, hold promise to mitigating the effects of ALS, whereas caloric restriction, malnutrition and high-intensity exercise are contraindicated in this disease model. CONCLUSIONS Improved nutritional status is of utmost importance in mitigating the detrimental effects of ALS.

Overweight and obese boys reduce food intake in response to a glucose drink but fail to increase intake in response to exercise of short duration

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.

Television Viewing at Mealtime Reduces Caloric Compensation in Peripubertal, But Not Postpubertal, Girls

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 < 0.001), primarily because of its effect in peripubertal girls (p < 0.028). In postpubertal girls (n = 8), glucose reduced FI by ∼27% in both the no TVV and TVV conditions, but in peripubertal girls (n = 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.)

Obesity, sex and pubertal status affect appetite hormone responses to a mixed glucose and whey protein drink in adolescents

Little information is available on how food intake regulatory hormones may be altered during pubertal development and across the weight spectrum in adolescents. Therefore, the effect of obesity, sex and pubertal status on subjective appetite and appetite hormones in response to a mixed glucose and whey protein drink was determined in 8–18 year old adolescents.

Pre- and within-meal effects of fluid dairy products on appetite, food intake, glycemia, and regulatory hormones in children

The effect of beverages commonly consumed by children in-between or with meals on short-term food intake (FI) and glycemic control has received little attention. Therefore, 2 experiments were conducted in 9- to 14-year-old children following a randomized repeated-measures design. Experiment 1 (n = 32) compared the effects of water (control) and isocaloric (130 kcal) amounts of 2% milk, chocolate milk, yogurt drink, and fruit punch on subjective appetite and FI. Experiment 2 (n = 20) compared the effects of isocaloric (130 kcal) amounts of 2% milk and fruit punch on subjective appetite, FI, and glycemic and appetite hormone responses. One serving of the beverages was given as a pre-meal drink at baseline (0 min) and a second serving 60 min later with an ad libitum pizza meal. Meal FI in experiment 1 was lower by 14% and 10%, respectively, after chocolate milk and yogurt drink (p < 0.001), but not milk, compared with water. Cumulative energy intake (beverages plus meal) was higher after caloric beverages than water. In experiment 2, no differences occurred in pre-meal but post-meal glucose was 83% higher in overweight/obese than normal-weight children (p = 0.02). Milk led to higher pre-meal glucagon-like peptide-1 and post-meal peptide tyrosine tyrosine (PYY) than fruit punch (p < 0.01) but insulin did not differ between treatments. In conclusion, dairy products consumed before and with a meal have more favourable effects on FI, appetite, and satiety hormones than a sugar-sweetened beverage, but all caloric beverages result in more cumulative calories than if water is the beverage.

Acute decrease in serum testosterone after a mixed glucose and protein beverage in obese peripubertal boys

Delayed puberty and lower levels of testosterone (T) have been observed in adult obese males and some adolescent males. In adult men, enteral glucose ingestion results in acute lowering of serum testosterone levels; however, this has not been studied in adolescents. We aimed to examine the acute effect of a glucose/protein beverage on serum T concentration changes in obese peripubertal males. A second objective was to determine whether change in T concentration was related to appetite hormone levels.

Pubertal status, pre-meal drink composition, and later meal timing interact in determining children's appetite and food intake.

Puberty is a period of development that alters energy intake patterns. However, few studies have examined appetite and food intake (FI) regulation during development of puberty in children and adolescents. Therefore, the objective was to measure the effect of pubertal status on FI and subjective appetite after pre-meal glucose and whey protein drinks in 9- to 14-year-old boys and girls. In a within-subject, randomized, repeated-measures design, children (21 pre-early pubertal, 15 mid-late pubertal) received equally sweetened drinks containing Sucralose (control), glucose, or whey protein (0.75 g/kg body weight) in 250 mL of water 2 h after a standardized breakfast on 6 separate mornings. Ad libitum FI was measured either 30 or 60 min later and appetite was measured over time. In pre-early and mid-late pubertal boys and girls there was no effect of sex on total FI (kcal). Glucose and whey protein drinks reduced calorie intake similarly at 30 min. But at 60 min, whey protein reduced FI (p < 0.001) compared with control and glucose in pre-early pubertal children, but not in mid-late pubertal children. However, sex was a factor (p = 0.041) when FI was expressed per kilogram body weight. Pubertal status did not affect FI/kilogram body weight in boys, but it was 32% lower in mid-late pubertal girls than at pre-early puberty (p = 0.010). Appetite was associated with FI in mid-late pubertal children only. In conclusion, pubertal development affects appetite and FI regulation in children.