The effects of low carbohydrate (CHO), high fat (LCHF) diets on adaptations to high-intensity exercise have recently gained interest. Consuming a LCHF may potentially decrease the ability to use CHO during exercise and impair high-intensity exercise adaptations. Therefore, the purpose of this investigation was to examine the importance of CHO timing while consuming a LCHF diet and completing a high-intensity exercise program. Eighteen resistance trained males were randomized into two treatment groups. Both groups completed 6 weeks of a high-intensity exercise training program with the first 2 weeks serving as familiarization to resistance training (RT) 3 days per week and completing one high-intensity interval training (HIIT) session. During the final 4 weeks, participants trained 5 days per weeks, three days of RT and two days of HIIT (repeated 30 s all out sprints). All participants consumed a LCHF diet (~25%, ~25%, and ~50% of daily kilocalorie intake coming from CHO, protein, and fat). The supplemented (SUPP) group (n=9) consumed 30 g of CHO during exercise and 40 g of CHO immediately after each exercise session. The remainder of the SUPP groups daily CHO intake came outside of training. The non-supplemented (NONSUPP) group (n=9) consumed an artificially flavored placebo during exercise. The NONSUPP group had the same daily CHO intake as the SUPP group, with the only difference being CHO timing. Dependent variables measured pre-and post-training included back squat and bench press one-repetition maximums, peak oxygen consumption (V̇O2 peak), power output (Wingate test), body composition, fasted glucose, insulin, and testosterone, and gastrointestinal distress (GID) during exercise. Both groups significantly improved back squat and bench press strength, biceps thickness, absolute and relative V̇O2 peak, and power output. Respiratory exchange ratio was significantly lower and time to exhaustion significantly increased during the post V̇O2 peak test. However, there were no changes in resting glucose, insulin, and testosterone or body fat. RT and HIIT caused significant increases in GID, independent of beverage content, with no differences between training. Our results suggest that CHO timing has no impact on adaptations to exercise training, but favorable training adaptations can be made while consuming a LCHF diet.

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京都大学 / 新制・課程博士 / 博士(医学) / 甲第24200号 / 医博第4894号 / 新制||医||1061(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 中本 裕士, 教授 江木 盛時 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The National Cholesterol Education Program Adult Treatment Panel guidelines specify that dietary intervention is the cornerstone of treatment for hypercholesterolemia. Self-monitoring is a strategy used to achieve self-direction in adopting and maintaining a cholesterol-lowering dietary pattern. The Cholesterol Saturated Fat Index (CSI) illustrates the atherogenic potential of food. Given that saturated fat and dietary cholesterol are the two major dietary components known to raise serum cholesterol, a CSI Scorecard was developed and pilot tested as a dietary self-monitoring tool. Twelve nutritionists scored the same five food records with known CSI scores, the reference data. The food records represented CSI scores from the 10th, 25th, 50th, 75th, and 90th percentiles from a pool of 400 usual diet food records. Two-tailed, one-sample t-tests demonstrated that the CSI Scorecard scores were not statistically significant at only the 25th and 75th percentiles. Therefore, in three of five food record percentiles, nutritionists’ CSI scores differed from the corresponding reference CSI scores. Small sample size and years of experience may have been factors influencing the results. Comments from the nutritionists’ critique forms were incorporated into the revision of the CSI Scorecard. Twelve participants scored their four-day food records using the booklet. The Spearman’s rho correlation of the CSI Scorecard derived CSI scores to the reference CSI scores was r_S=.8 (p<.05). These preliminary results and comments from the formative evaluation meetings suggested that the CSI Scorecard deserves further validity testing with a larger sample of subjects. The CSI Scorecard appeared to show promise as a dietary self-monitoring tool that would facilitate increased self-direction in the adoption of a cholesterol-lowering diet. / Master of Science

Background: Modifying the gut microbiota through the administration of probiotics during high fat feeding has been shown to attenuate weight gain and body fat accretion while improving insulin sensitivity in animal models. Objective: Our objective was to determine the effects of the probiotic VSL#3 on body weightand composition, skeletal muscle substrate oxidation, and insulin sensitivity and during 4 weeks of high-fat, hypercaloric feeding. We hypothesized that the probiotic would attenuate the body weight and fat gain and adverse changes in insulin sensitivity and substrate oxidation following high fat, hypercaloric feeding in young, non-obese males. Methods: Twenty non-obese males (18-30 y) volunteered to participate in the present study. Following a 2-week eucaloric control diet, subjects underwent a dual x-ray absorptiometry (DXA) to determine body composition, an intravenous glucose tolerance test (IVGTT) to determine insulin sensitivity, a skeletal muscle biopsy for measurement of substrate oxidation. Serum endotoxin was also measured. Subsequently, subjects were randomized to receive either VSL#3 (2 satchets) or placebo during 4 weeks of consuming a high fat (55% fat), hypercaloric diet (+1,000 kcal/day). Macronutrient composition of the high fat diet was 55% fat, 30% carbohydrate, and 15% protein. Results: There were no differences between the groups in subject characteristics or in the dependent variables at baseline. Body weight and fat mass increased less (P<0.045) following the high fat diet with VSL#3 compared to placebo. Insulin sensitivity (and other IVGTT variables) and both glucose and fat oxidation did not change significantly with time or VSL#3 treatment. Serum endotoxin concentration was not different between groups following the high-fat diet. Conclusions: VSL#3, a multi-strain probiotic, attenuated body weight and fat gain following a 4-week high fat, hypercaloric diet compared with a placebo. There were no differences between the VSL and control in circulating endotoxin, insulin sensitivity (and other IVGTT variables) or in skeletal muscle substrate oxidation. / Ph. D.

High-fat diets and obesity have been linked to unfavorable changes in gut bacteria and increased leakage of bacterially-derived lipopolysaccharide (endotoxin) from the intestinal tract into circulation, which is associated with low-grade inflammation, metabolic dysregulation and degradation of tight-junction proteins between intestinal cells. Probiotic supplementation is the practice of ingesting live strains of bacteria that are proposed to have a beneficial effect on the host by enriching the intestine with healthy bacteria. The purpose of this project was to determine if probiotic supplementation would prevent increased inflammatory tone, decreased oxidative capacity, and decreased tight-junction protein expression associated with high-fat feeding and elevated endogenous endotoxin. Male C57BL/6J mice were fed either a control (CD, 10% fat) or high-fat (HFD, 60% fat) diet for 4 weeks while receiving a daily oral gavage of water (C-VSL#3, HF-VSL#3) or probiotics (C+VSL#3, HF+VSL#3) equivalent to 1.2 billion live cultures. Changes in body weight, body composition, respiratory exchange ratio, energy expenditure, and glucose and insulin tolerance were measured in live mice. Markers of metabolic function were measured in whole muscle homgenates and mitochondria isolated from red and white skeletal muscle. Plasma endotoxin was measured in blood collected from fasted mice at the time of euthanization. The large and small intestines were collected and mRNA levels of tight-junction proteins and markers of nutrient sensing were measured. To determine a possible protective effect against endogenous LPS, a second cohort of mice were given an intraperitoneal injection of 0.1µg/kg LPS or saline to induce endotoxemia after four weeks of the aforementioned feeding protocol. Markers of metabolic function and inflammation were measured in mitochondria, skeletal muscle and liver. VSL#3 supplementation improved glucose homeostasis and markers of inflammation while enhancing nutrient sensing in the gut. / Ph. D.

Insulin resistance (IR), T2DM, and obesity together form a cluster of interrelated metabolic challenges that may be linked by metabolic inflexibility. Metabolic inflexibility is characterized by the resistance to switching substrate oxidation preference based on substrate availability and can be measured in either fasted or insulin-stimulated conditions. As the largest site for glucose disposal and a primary tissue influencing regulation of blood glucose concentrations, skeletal muscle likely plays a central role in regulating substrate oxidation preference based on substrate availability. Skeletal muscle lipotoxicity caused by an impaired regulation of fat uptake and oxidation is postulated to disrupt insulin signaling and lead to skeletal muscle IR. High dietary saturated fat intake results in reduced basal fat oxidation and a resistance to switching to carbohydrate oxidation during insulin-stimulated conditions in susceptible individuals. This metabolic inflexibility may lead to an accumulation of intramyocellular species that impair insulin signaling. Endurance exercise training improves the capacity for fat oxidation in metabolically inflexible individuals. However, relatively little is known about how endurance exercise training influences substrate oxidation preference when paired with a high fat diet (HFD). Therefore, the purpose of this study was to determine the effects of a HFD on substrate metabolism in skeletal muscle of sedentary and endurance trained (ET) males. Healthy, sedentary (n=17) and ET (n=7) males first consumed a 10-day moderate carbohydrate diet (55% carbohydrate, 30% total fat, <10% saturated fat) isocaloric to their individual energy requirements and then underwent a 4- hour high fat challenge testing session. During the session, they consumed a high fat meal (820 kcals; 25% carbohydrate, 63% total fat [26% saturated fat]), and skeletal muscle biopsies were taken in the fasted and 4-hour postprandial conditions. Participants then consumed a 5-day HFD (30% carbohydrate, 55% total fat, 25% saturated fat) and repeated the high fat challenge testing session. Substrate oxidation measures were performed on the collected skeletal muscle tissue, and the meal effect, defined as the percent change from the fasting to 4- hour postprandial condition, for each measure was calculated. There was a HFD by physical activity group interaction on meal effect for metabolic flexibility (P<0.05) and a HFD effect on meal effect for glucose oxidation (P<0.05). Meal effects for metabolic flexibility and glucose oxidation were maintained in the ET (20 ± 4% to 41 ± 21% and 128 ± 92% and 41 ± 15%, respectively; both P>0.05) but decreased in the sedentary (34 ± 7% to 4 ± 5% and 78 ± 26% to -21 ± 6%, respectively; both P<0.01) group. There were trends toward HFD effects on reductions in meal effects for total (P=0.062) and incomplete (P=0.075) fat oxidation, which were driven primarily by an increase in fasting total (12.1 ± 2.6 nmol/mg protein/h to 18.5 ± 2.3 nmol/mg protein/h; P<0.01) and incomplete (11.5 ± 2.5 nmol/mg protein/h to 17.6 ± 2.3 nmol/mg protein/h; P<0.01) fat oxidation in the ET group as a result of the HFD. Fasting total and incomplete fat oxidation did not change in the sedentary group (7.3 ± 0.8 nmol/mg protein/h to 7.8 ± 0.8 nmol/mg protein/h and 6.8 ± 0.7 nmol/mg protein/h to 7.2 ± 0.8 nmol/mg protein/h, respectively; both P>0.05). Overall, these findings suggest the ET state attenuates deleterious effects of a short-term HFD on reduced metabolic flexibility and insulin-stimulated glucose oxidation. In addition, a HFD-induced reduction in fat oxidation during the fasted-to-fed transition may be caused by differing mechanisms in sedentary and ET individuals. These findings provide a basis for future work targeting the elucidation of potential mechanistic differences in substrate oxidation preference between sedentary and ET individuals. / Ph. D. / Type 2 diabetes (T2DM) is a commonly occurring disease worldwide, and treatment of the disease is considerably burdensome for individuals and societies. T2DM is closely related to insulin resistance (IR) and obesity, and in each of these conditions, the characteristic of metabolic inflexibility has been observed. Metabolic inflexibility is a reduced ability to adjust fat or carbohydrate utilization for energy based on the availability of each of these macronutrients. Skeletal muscle may be an important tissue in the regulation of macronutrient utilization since it plays a key role in blood glucose regulation. High dietary saturated fat intake may lead to metabolic inflexibility in skeletal muscle in susceptible individuals. This metabolic inflexibility may result in increased storage of fat within skeletal muscle, which is hypothesized to disrupt insulin signaling. This disruption can lead to IR. Endurance exercise training improves metabolic flexibility. However, little is known about how endurance exercise training influences macronutrient utilization when paired with a high fat diet (HFD). Therefore, the purpose of this study was to determine the effects of a HFD on macronutrient utilization in skeletal muscle of sedentary and endurance trained (ET) males. Seventeen healthy, sedentary males and seven ET males first consumed a 10-day moderate-carbohydrate diet that was provided by the study investigators and designed to keep each participant weight stable. Participants then underwent a high fat challenge testing session in which they consumed a high fat meal and had skeletal muscle biopsies taken both before and after the meal. Participants then consumed a 5-day HFD, also designed to keep them weight stable, and repeated the high fat challenge testing session. Macronutrient utilization measures were performed on the collected skeletal muscle samples. Overall, metabolic flexibility was reduced in the sedentary group but was maintained in the ET group, which suggests that ET individuals may be protected against developing a HFD-induced metabolic inflexibility in skeletal muscle and its associated downstream negative effects on insulin signaling. In addition, fat utilization during the high fat challenge meal decreased in both sedentary and ET individuals as a result of the HFD. However, fat utilization in the fasted state was higher in ET individuals after the HFD compared with baseline, but fat utilization was the same in sedentary individuals before and after the HFD. This suggests there may be differences between sedentary and ET individuals in the mechanisms involved in the adjustment of fat utilization to dietary fat intake. Further research is needed to understand these differences, as they may play important roles in understanding how IR and T2DM develop.

2 pp. / Of all the nutrients in the food supply, fat and cholesterol probably receive the most attention from health professionals and the public alike. The scientific evidence is clear that a high-fat diet relates to chronic health problems such as heart disease, some types of cancer, diabetes, and obesity. But both fat and cholesterol are natural components of the body that are vital to good health, and too little fat in your diet is just as unhealthy as too much. This article reviews dietary fats and provides guidelines for choosing foods to balance the type and amount of fat in your diet.

The composition of the diet has been recently researched as an important factor in controlling excess body fat, and thus obesity. Along with dietary modifications, it has been stressed to incorporate behavior modification and daily physical activity to promote weight loss. A comprehensive program incorporating all three components is the suggested treatment for long term weight maintenance. This study investigated a 12 week low dietary fat education program including behavior modification and physical activity to promote weight loss in the abdominally obese. There were eight experimental subjects and four controls. Measurements assessed were height, weight, percent body fat, body mass index, waist/hip ratio, ideal body weight, daily caloric intake, percent dietary fat intake, percent saturated fat intake, saturated fat gram intake, physical activity assessments and resting metabolic rate. Results showed significant differences between the experimental and control groups for calorie intake, body weight, ideal body weight and saturated fat gram intake at post-intervention. Percent of dietary fat intake decreased from baseline to follow-up in the experimental group, but did not reach significance. There was a 33% decrease in saturated fat gram intake from baseline to follow-up in the experimental group. A significant decrease in daily caloric intake occurred in the experimental group from baseline to post-intervention. The decrease in body weight could not be directly correlated to dietary fat intake, although they did have a tendency to move in the same direction. These data suggest the weight management program in this study was successful at decreasing body weight, daily caloric intake, dietary fat intake and saturated fat intake.The qualitative interview revealed obstacles faced by the subjects. The most common difficulties in adhering to the program included time constraints, travel, lack of a structured physical activity component, social pressures triggering eating behavior, feeling of guilt when prioritizing time for oneself and lack of continued support and education through class sessions. Individual motivational factors existed. Therefore, personalized attention and a continued support system would be beneficial as part of the treatment program for success in changing lifestyle behaviors.In conclusion, this data suggest an educational program encouraging decreased dietary fat intake, behavior modification and increased daily physical activity without a calorie controlled plan can promote weight management in the abdominally obese. / Institute for Wellness