Individuals with abdominal obesity are at higher risk for developing type 2 diabetes, predisposing cardiovascular events and insulin resistance. Low glycemic index (GI) diets may be beneficial in the management of insulin resistance. Insulin resistance is associated with increased intramyocellular lipid (IMCL) content as measured by proton nuclear magnetic resonance spectroscopy (1H-MRS). The primary objective of this thesis was to determine whether a low GI diet can improve insulin sensitivity by reducing IMCL of skeletal muscle. One hundred and twenty-one male and female participants aged 30 to 70 years (mean+SD, 53+10)) with abdominal obesity, entered a 4 to 6 week weight-maintaining, low-fat dietary advice run-in phase. Of the 121 eligible participants, 95 completed the run-in phase and were randomly assigned to either a low-GI (LGID, n=48) or high-GI diet (HGID, n=47) for 24 weeks. Participants underwent a 75g oral glucose tolerance test (OGTT) and had soleus-muscle IMCL measured by 1H-MRS at the beginning and end of the intervention period. Insulin sensitivity was assessed by the homeostatic model assessment index (HOMA) and the insulinogenic index (ISI) was calculated for insulin secretion. At the end of the run-in phase, there were significant reductions in serum total-, LDL-, and HDL-cholesterol (all, p<0.0001) and an increase in fasting plasma glucose (p<0.05). In 57 participants who wore a continuous glucose monitoring system for 24 hours during the run-in period, a total of 30% (p<0.001) of the variation in the incremental area under the blood glucose curve after self-selected breakfast meals was explained by GI. After 24 weeks, diet GI was significantly lower in the LGID than HGID group (55.5+3.1 vs 63.9+3.1, p<0.0001). Plasma glucose 60 minutes after the OGTT was significantly lower on the LGID than at baseline (p<0.05) and there was a non-significant trend towards an increase in ISI (p=0.07). On the HGID, ISI increased significantly from baseline (p<0.01). It is concluded that the LGID reduced 60 minute plasma glucose but did not significantly affect IMCL or insulin sensitivity in individuals with abdominal obesity.

Individuals with abdominal obesity are at higher risk for developing type 2 diabetes, predisposing cardiovascular events and insulin resistance. Low glycemic index (GI) diets may be beneficial in the management of insulin resistance. Insulin resistance is associated with increased intramyocellular lipid (IMCL) content as measured by proton nuclear magnetic resonance spectroscopy (1H-MRS). The primary objective of this thesis was to determine whether a low GI diet can improve insulin sensitivity by reducing IMCL of skeletal muscle. One hundred and twenty-one male and female participants aged 30 to 70 years (mean+SD, 53+10)) with abdominal obesity, entered a 4 to 6 week weight-maintaining, low-fat dietary advice run-in phase. Of the 121 eligible participants, 95 completed the run-in phase and were randomly assigned to either a low-GI (LGID, n=48) or high-GI diet (HGID, n=47) for 24 weeks. Participants underwent a 75g oral glucose tolerance test (OGTT) and had soleus-muscle IMCL measured by 1H-MRS at the beginning and end of the intervention period. Insulin sensitivity was assessed by the homeostatic model assessment index (HOMA) and the insulinogenic index (ISI) was calculated for insulin secretion. At the end of the run-in phase, there were significant reductions in serum total-, LDL-, and HDL-cholesterol (all, p<0.0001) and an increase in fasting plasma glucose (p<0.05). In 57 participants who wore a continuous glucose monitoring system for 24 hours during the run-in period, a total of 30% (p<0.001) of the variation in the incremental area under the blood glucose curve after self-selected breakfast meals was explained by GI. After 24 weeks, diet GI was significantly lower in the LGID than HGID group (55.5+3.1 vs 63.9+3.1, p<0.0001). Plasma glucose 60 minutes after the OGTT was significantly lower on the LGID than at baseline (p<0.05) and there was a non-significant trend towards an increase in ISI (p=0.07). On the HGID, ISI increased significantly from baseline (p<0.01). It is concluded that the LGID reduced 60 minute plasma glucose but did not significantly affect IMCL or insulin sensitivity in individuals with abdominal obesity.

Made available in DSpace on 2016-06-02T20:21:32Z (GMT). No. of bitstreams: 1 5576.pdf: 1152832 bytes, checksum: 13ad2d45c47c55991a6ab0c41eebb5e1 (MD5) Previous issue date: 2013-09-27 / Financiadora de Estudos e Projetos / Introduction: The skeletal muscle is the largest tissue present in vertebrates and is involved in locomotion, posture and breathing movements. It is composed of elongated, cylindrical and multinucleated muscle fibers with fat droplets in the sarcoplasma, known as intramyocellular lipid (IMCL) used as energy during exercise. Another source of energy used by the muscle is the carbohydrate stored in the body as glycogen, which is stored in the liver and muscle fibers. Muscle fibers are also surrounded by an extracellular matrix (ECM) formed, among other components, by collagen, mainly types I, III, IV and V. The aging process is associated with loss of muscle mass, muscle strength and function, increase of IMCL, reduction in glycogen synthesis with consequent insulin resistance, and also fibrosis and deposition of ECM. On the other hand, strength training (TF) is considered appropriate intervention to modify, minimize or reverse some physiological changes in skeletal muscle, as a result of aging. Thus, this study aimed to assess the cross section area of skeletal muscle fibers, amount of IMCL, glycogen content and MEC properties of the gastrocnemius (GAM) and soleus (SO) of young and senile rats after TF protocol. Methods: 28 rats were randomly divided into 4 groups: Youth (J); Old(S); Youth who underwent strength training (JT); Old who underwent strength training (ST). The animals performed strength training protocol consisting in climb a vertical ladder with weight strapped in their tails of 65%, 85%, 95% and 100% of the maximum load of the animal 3x a week for 12 weeks. CSA of muscle fibers, detection of collagen and identification of adipocytes in the GAM and SO muscles, beyond determinations of glycogen in the liver and skeletal muscle were performed. Results: Senile animals had lower CSA values, greater amount of IMCL, as well as of connective tissue in both muscles, but did not change the glycogen content in liver and muscle. After TF, the CSA increased in young and old animals in both muscles, the reduced IMCL in SO muscle of old animals, connective tissue decreased in young and old animals in both muscle and, finally, the glycogen content increased in liver and muscle of young and old animals. Conclusion: The strength training protocol in old rats was able to increase the CSA, decrease IMCL, increase of stored glycogen and decrease the connective tissue present in GAM and SO muscles. These results showed that there are changes in muscle fiber size, in the quantity of IMCL, in glycogen storage and in properties of the ECM of the GAM and SO muscle after intervention, indicating that strength training minimizes some deleterious effects inherent aging. / Introdução: O músculo estriado esquelético forma o maior tecido presente nos vertebrados e está envolvido na locomoção, postura e movimentos respiratórios. É formado por fibras musculares alongadas, cilíndricas e multinucleadas cujo sarcoplasma apresenta gotículas de gordura, conhecidas como lipídeo intramiocelular (IMCL), e utilizadas como combustível durante o exercício. Outra fonte de energia utilizada pelo músculo é o carboidrato, estocado no corpo como glicogênio que, por sua vez, é armazenado no fígado e dentro das fibras musculares. Essas fibras também estão envoltas por uma matriz extracelular (MEC) formada, entre outros componentes, pelo colágeno, principalmente, dos tipos I, III, IV e V. No músculo esquelético, o processo de envelhecimento está associado com a perda de massa, força e função muscular, aumento de IMCL, diminuição na síntese de glicogênio com, conseqüente, resistência à insulina, além de fibrose e deposição de MEC. Por outro lado, o treinamento de força (TF) é considerado uma intervenção apropriada para alterar, diminuir ou reverter parcialmente algumas alterações fisiológicas que ocorrem no músculo esquelético durante o processo de envelhecimento. Desta forma, o presente trabalho objetivou avaliar o tamanho das fibras musculares, a quantidade de IMCL, o armazenamento do glicogênio e as propriedades da MEC dos músculos gastrocnêmio (GAM) e sóleo (SO) de ratos jovens e senis após protocolo de treinamento de força. Metodologia: 28 animais foram distribuídos aleatoriamente em 4 grupos experimentais: Jovens (J); Senis (S); Jovens que realizaram treinamento de força (JT); Senis que realizaram treinamento de força (ST). Os animais realizaram protocolo de treinamento de força que consistia em escalarem uma escada vertical com pesos, presos em suas caudas, de 65%, 85%, 95% e 100% da capacidade máxima de carregamento do animal, durante 12 semanas e com freqüência de 3x por semana. Foram realizadas contagem e morfometria da área de secção transversa (CSA) das fibras musculares, detecção de colágeno e identificação de adipócitos nos músculos GAM e SO, além das determinações de glicogênio muscular e hepático, seguido de análise estatística. Resultados: Os animais senis apresentaram menor valor de CSA, maior quantidade de IMCL e maior quantidade de tecido conjuntivo em ambos os músculos, porém não apresentou alterações na quantidade de glicogênio armazenada nos músculo e no fígado. Após o TF, houve aumento na CSA dos animais jovens e senis em ambos os músculos, diminuição na quantidade de IMCL no músculo SO dos animais senis, redução do conteúdo de tecido conjuntivo nos animais jovens e senis em ambos os músculos e, por fim, aumento no armazenamento de glicogênio no músculo e fígado dos animais jovens e senis. Conclusão: O protocolo de treinamento de força realizado em ratos senis foi capaz de aumentar a CSA, diminuir a quantidade de IMCL, aumentar a quantidade de glicogênio armazenado e diminuir a quantidade de tecido conjuntivo presente nos músculos esqueléticos GAM e SO. Esses resultados mostram que há alterações no tamanho das fibras musculares, na quantidade de IMCL, no armazenamento de glicogênio e nas propriedades da MEC nos músculos estudados após a intervenção, comprovando que o treinamento de força minimiza os efeitos deletérios inerentes ao envelhecimento.

During mechanical ventilation the diaphragm experiences an extreme case of muscleunloading. In many cases this results in respiratory muscle dysfunctions making it difficult towean the patient off the ventilator. One component in this dysfunction is the accumulation ofintramyocellular lipids (IMCL) in the diaphragm muscle fibres. Using Oil Red O stainingsand confocal microscopy on rat diaphragm sections we have quantified this process. Theresults show a sudden increase in IMCL contents between 18 and 24 hours. No significantdifference between fibre types could be seen.

Intramyocellular lipid (IMCL), an ectopic fat depot found within skeletal muscle fibers, is highly associated with obesity and strongly correlated with insulin resistance. IMCL accumulation in sedentary individuals may contribute to insulin resistance by interfering with insulin signaling in skeletal muscle, leading to inadequate glucose uptake by the cell. Lipid peroxidation is also associated with both obesity and insulin resistance, and with IMCL, but a relationship has yet to be established among all of these variables. The purpose of this project is to study for the first time the relationships among lipid peroxidation, IMCL content, and glucose uptake in skeletal muscle. Nine insulin-sensitive adults (IS), 13 insulin-resistant adults (IR), 10 diabetic (DB) and 8 subjects pre- and post- 12-week intervention with insulin-sensitizing thiazolinedione (TZD) were assessed for soleus IMCL with nuclear magnetic resonance, insulin sensitivity by both hyperinsulinemic-euglycemic clamp (GDR) and homeostasis model assessment index (HOMA1), and anthropometrics, including body mass index (BMI), percent fat by DEXA scan, and waist circumference. Vastus lateralis biopsies of all subjects were homogenized and analyzed by immunoblotting for post-translational protein modifications occurring from lipid-peroxidation (HNE). GDR and HOMA were significantly different among IS, IR, and DB groups, as expected, as were waist circumference and BMI. IMCL was significantly higher in DB than in IS and IR. HNE was also higher in DB than in IS, although it did not differ from IR. HNE was significantly correlated to GDR, HOMA1, and BMI, but not to IMCL, WAIST, or percent fat measures. IMCL showed a strong, negative correlation with GDR and was the primary, independent predictor of GDR in stepwise multiple regression. HNE was the primary, independent predictor of HOMA in stepwise multiple regression. Paired t-tests revealed improvements in insulin sensitivity measures after 12 weeks of TZD intervention, but no significant differences were observed in IMCL or HNE after intervention. These data show that skeletal muscle HNE and IMCL are both determinants of insulin resistance in obese, sedentary adults. HNE and IMCL are not related and therefore impact insulin resistance independently. These results reveal, for the first time, a negative relationship between skeletal muscle HNE and insulin sensitivity in sedentary individuals and underscore the importance of lipid peroxidation in insulin resistance.