<p>Energy restriction-induced weight loss results in the loss of both fat mass (FM) and fat free mass (FFM). Declines in FFM, comprised mostly of skeletal muscle, have the potential to impair metabolic health. A recent meta-analysis demonstrated higher protein hypo-energetic diets (≥ 1.25 g/kg/d) can help retain FFM (Weinheimer, Sands, & Campbell, 2010). This effect is attributed to protein ingestion induced stimulation of muscle protein synthesis (MPS), which is dependent on protein source (Tang, Moore, Kujbida, Tarnopolsky, & Phillips, 2009). However, protein source on modulating FFM preservation during ER remains understudied. In a double blind investigation, 40 adults (BMI 28-40) undertook a moderate 14 day hypo-energetic diet. Subjects were randomized to be supplemented twice daily with whey (WHEY) or soy (SOY) protein, or a carbohydrate (CHO) powder as part of their ER diet. Preliminary and post diet intervention testing included skeletal muscle biopsies, blood samples and DXA measures. Absolute changes in body mass (-2.3 ± 0.18 kg), FM (-1.2 ± 0.16 kg) and FFM (-0.8 ± 0.24 kg) did not significantly differ between groups. Basal serum cortisol was unchanged in WHEY but increased significantly in SOY and CHO (p</p> / Master of Science in Kinesiology

Osteoporosis which is frequently referred to as a pediatric disease with geriatric consequences (Golden, 2000) can result from a lack of optimal bone accrual during the development (NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, 2001). Pubertal timing is a key factor that contributes to optimal bone accrual and strength (Bonjour et al., 1994; 21 Warren et al., 2002). Bone mass doubles during the onset of puberty and young adulthood (Katzman et al., 1991) with more than 90% of peak bone mass being accrued at the end of second decade of life (Schneider & Wade, 2000). The rate of periosteal expansion is elevated during the pubertal period (Specker et al., 1987; Bradney et al., 2000) and this expansion parallels longitudinal growth (Parfitt, 1994). Irrespective of other changes, periosteal expansion lowers fracture risk by improving the strength of long bones by increasing the moment of inertia (Orwoll, 2003). Therefore, a delay in puberty may actually increase the time available for periosteal development and positively affect bone strength. Previous animal studies have shown decreases in strength, endocortical bone formation and increases in periosteal bone formation with delayed puberty. Clinical studies report negative effects of delayed puberty on bone mass accrual suggesting that delayed puberty is a multifactorial problem affecting bone strength development. The purpose of this study was to determine the effect of delayed puberty on mechanical strength and endocortical bone marrow cells in two models: female rats treated with gonadatropin releasing hormone antagonists (GnRH-a) and energy restriction (30%). Thirty-two female Sprague Dawley rats (21 to 22 days-of-age) were received from (Charles Rivers Laboratories, Wilmington, MA, USA) and housed individually at the Temple University Central Animal Facility (Temple University Weiss Hall). Animals were randomly assigned to one of three groups; control (n=10), GnRH-a (n=10) and energy restriction (ER) (n=12). The GnRH-a group was injected with gonadotropin releasing antagonist injections (GnRH-a) (Antide, Bachem, Torrance, Ca. USA) at a dose of 2.5 mg/kg/BW. The ER group received a 30% energy restricted diet (0pen Source diet (D07100606)(Research Diets, New Brunswick, NJ). All animals were sacrificed on Day 51. One way analysis of variance testing (ANOVA) with a significance level of 0.05 was used to assess group differences. Following the two protocols the uterine weight in the GnRH-a group was 80.6% lower than control; no change in the ER group. Ovarian weight was significantly lower in the GnRH-a group (83.3%) and in the ER group (33.3%) as compared to controls. A 22.7% lower muscle weight was found in the ER group but was equal to control and GnRH-a when normalized by body weight (BW). The retro-peritoneal fat pad weight was significantly decreased by 64.95% in the ER group as compared to controls. Energy restriction did not result in any deficit in bone strength when normalized by body weight however the GnRH-a group had a 26.2% lower bone strength compared to control. Histomorphometric changes were not significantly different between groups, but the ratio for periosteal versus endocortical bone formation rates for the control group was 1.38, GnRH-a was significantly higher with a ratio of 5.54 and for ER was 3.02 indicating that periosteal BFR are almost twice endocortical BFR in the experimental groups. There was a significant decrease in the trabecular percent bone volume (BV/TV) of the lumbar vertebra in the GnRH-a group (20.2%) compared to control. However BV/TV was significantly higher in the ER (18.4%) compared to the control group. Proliferation was suppressed to 59.6% of control in the GnRH-a group but only 85.5% of control in the ER group. The alkaline phosphatase activity was 31.2% lower in the GnRH-a group and 63.9% lower in the ER group. The relative quantification (RQ) of RUNX2 gene expression was lowest in control followed by GnRH-a and highest in ER group although no statistical significance was observed between any groups. Thus our data infers that 30% energy restriction does not negatively impact bone health. Thirty percent food restriction with no deficits in micronutrients or hormone suppression may just suppress growth as indicated by the maintenance of bone strength per body weight and equivalent muscle mass per body weight in the ER group compared to control. The GnRH-a injections resulted in decreased bone strength and trabecular bone volume. Female Athlete Triad or Anorexia Nervosa are the two clinical conditions hypothesized to result from a combination of ER and estrogen deficient environment. Studies replacing estrogen in hypothalamic amenorrhea or IGF-1 in anorexia alone have failed to improve bone mineral density (BMD), but a combination of IGF-1 and estrogen has been successful in improving BMD. This suggests that estrogen dependant and independent mechanisms work in combination to protect bone. Our study investigated both mechanisms separately and indicates that ER at 30% may be protective for bone health. Since estrogen deficiency may be the extreme end of the spectrum affecting trabecular bone, treatment therapies may have to be based on age, magnitude and severity of energy restriction and presence or absence of menstrual status. / Kinesiology

The late second and early third decades of life are critical periods for bone health due to the attainment of peak bone mass during this time, yet little is known about relationships between lifestyle factors and bone health among young-adult females. Therefore, anthropometric, body composition, and nutritional variables were examined in relation to bone mineral density (BMD) and biochemical markers of bone turnover in a group of 60 healthy, young-adult females aged 18 to 25 years. Body weight, body mass index (BMI), fat-free soft tissue mass (FFST), and fat mass had statistically significant and positive associations with BMD. Mean daily dietary protein, magnesium, and iron intakes had statistically significant and negative associations with BMD. A second study compared dietary intake, BMD, and biochemical markers of bone turnover in young-adult females with chronic dieting habits to nondieters. Anthropometric and body composition variables between chronic dieters and nondieters were not statistically different; however, chronic dieters had statistically significantly lower average daily dietary intakes of energy, macronutrients, and selected micronutrients compared to nondieters. Chronic dieters had statistically significantly higher whole body (WB) BMD compared to nondieters. Moderate effects were observed for WB, lumbar spine, trochanter, and total proximal femur BMD such that chronic dieters possessed greater BMD compared to nondieters. It appears that among young-adult females, total body weight, particularly FFST mass, has an important association with BMD. Although nutritional inadequacies among young-adult females raise concerns, overconsumption of nutrients may increase the likelihood of nutrient-nutrient interactions that may have a less than optimal impact on BMD. Future investigations of dietary intake and BMD among young-adult females are warranted. / Master of Science

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L’absence de réponse et la résistance des cellules cancéreuses mammaires aux thérapies actuelles justifient de développer de nouveaux traitements. Une stratégie prometteuse consiste à cibler le métabolisme énergétique des cellules cancéreuses. Dans ce contexte, des thiazolidinediones (TZD) présentent des effets antiprolifératifs qui pourraient résulter d’une atteinte du métabolisme énergétique. Notre laboratoire étudie des TZD dérivées de la troglitazone (TGZ). Durant cette thèse, nous avons cherché à déterminer si la Δ2-Troglitazone (Δ2-TGZ) modifie le métabolisme énergétique des cellules cancéreuses mammaires. Jusqu’à présent, les expériences menées au laboratoire étaient réalisées dans un milieu de culture contenant 1% de sérum de veau fœtal (SVF) qui crée un stress peu propice à l’étude du métabolisme. Nous avons donc d’abord caractérisé les effets de la Δ2-TGZ dans un milieu de culture contenant 10% SVF. Dans ces conditions, la Δ2-TGZ diminue toujours la prolifération des cellules cancéreuses mammaires, mais les doses requises sont plus élevées. En outre, la Δ2-TGZ induit des effets cytostatiques plutôt que l’apoptose. Nous avons ensuite montré que la Δ2-TGZ induit une perturbation du métabolisme énergétique, consistant en un blocage de la respiration mitochondriale que les cellules semblent compenser en stimulant la glycolyse. En parallèle, nous avons caractérisé le mode d’action du 2-désoxyglucose dont l’action antiproliférative dans les cellules cancéreuses mammaires est due à l’inhibition de la glycolyse et à la perturbation de la N-glycosylation des protéines. Il reste à déterminer la part des altérations métaboliques dans l’action anti-cancéreuse de la Δ2-TGZ / The absence of response and the resistance of cancer cells to therapies are strong arguments for the development of new therapeutic strategies. Data from the literature suggest that it could be interesting to target energy metabolism of cancer cells. In this context, thiazolidinediones (TZDs) display antiproliferative effects that could be the result of energy metabolism alteration. During this PhD, we aimed at determining if Δ2-Troglitazone (Δ2-TGZ) could modify energy metabolism of breast cancer cells. The experiments performed previously used a culture medium containing 1% of fetal calf serum (FCS) that is rather a stress inducing condition that can disturb cell metabolism. Thus, we first characterized the effects of Δ2-TGZ in a 10% FCS containing medium. In this case, Δ2-TGZ still decreases cell proliferation of breast cancer cells, but it requires high doses. Besides, Δ2-TGZ induces cell cycle arrest instead of apoptosis. Then, we have shown that Δ2-TGZ induced modifications of energy metabolism, which are due to a decrease in oxidative phosphorylation. We also observed an increase in glycolytic activity that is probably a compensatory mechanism. During this part of our work, we have also characterized the mechanisms involved in the anticancer activity of 2-deoxyglucose. We have shown that in breast cancer cells, this compound acts not only by glycolysis inhibition but also by protein N-glycosylation alteration. We have now to determine the part of metabolic alterations that are involved in the anti-cancer effects of Δ2-TGZ

By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

Bakgrund: Allt fler individer i välutvecklade länder kan klassificeras som överviktiga. Övervikt och fetma ökar risken för en mängd olika sjukdomar och är en av de främsta orsakerna till sjukdomsbördan och för tidig död i Sverige. Det finns därför behov för att kunna rekommendera effektiva kostinterventioner. Kontinuerlig energirestriktion är den vanligaste kostinterventionen, men det finns behov för att kunna rekommendera alternativa kostinterventioner.Syfte: Syftet med denna litteraturstudie var att sammanställa resultaten från randomiserade kontrollerade studier från de senaste fem åren som undersöker effekten av intermittent fasta och tidsbegränsat energiintag jämfört med kontinuerlig energirestriktion på viktreduktion och kroppskomposition.Metod: Litteratursökningen gjordes i databaserna Web of Science och PubMed. Sökningen resulterade i 612 träffar varav tio inkluderades i studien.Resultat: Tre av tio studier påvisade skillnader mellan kostinterventionerna gällande viktreduktion; en till fördel för intermittent fasta jämfört med kontinuerlig energirestriktion (p&lt;0,01) en till fördel för tidsbegränsat energiintag jämfört med kontinuerlig energirestriktion (p&lt;0,05) och en till fördel för kontinuerlig energirestriktion jämfört med intermittent fasta (p&lt;0,05). Två av tio studier påvisade skillnad mellan kostinterventionerna i mängden tappad fettmassa till fördel för intermittent fasta (p&lt;0,01) och tidsbegränsat energiintag (p&lt;0,05) jämfört med kontinuerlig energirestriktion.Konklusion: Intermittent fasta och tidsbegränsat energiintag har i denna litteraturöversikt visat på likvärdiga resultat på viktreduktion och kroppskomposition jämfört med kontinuerlig energirestriktion. Resultaten i de granskade studierna tyder på att det är följsamheten av kostinterventionen som är avgörande för viktreduktion och inte själva kostinterventionen i sig. / Background: There is an increase in overweight and obese people around the world. Overweight and obesity increases the risk of multiple diseases and comorbidities. Continuous energy restriction is the most used diet method. However, research suggests that adherence to the diet diminishes within a couple of months, therefore research in alternative methods has increased. Objectives: The objectives of this literature review were to review the latest literature since 2017 regarding the effects of intermittent fasting and time-restricted feeding compared to continuous energy restriction on weight loss and body composition.Methods: The literature search was done in Web of Science and PubMed. The search resulted in 612 articles. Ten of the 612 articles were included in the literature review.Results: Three out of ten studies showed significant differences between groups regarding weight loss. One in favor of intermittent fasting compared to continuous energy restriction (p&lt;0,01), one in favor of time-restricted feeding compared to continuous energy restriction (p&lt;0,05) and one in favor of continuous energy restriction compared to intermittent fasting (p=0,03). Two out of ten studies showed a significant difference between groups regarding reduction of fat mass in favor of intermittent fasting (p&lt;0,01) and time-restricted feeding (p&lt;0,05) compared to continuous energy restriction.Conclusion: This literature review suggests that intermittent fasting and time-restricted feeding when compared to continuous energy restriction has similar effects on weight loss and body composition. The results of the studies suggest that it is the adherence of the diet that is vital for successful weight loss and not the diet itself.