Browsing by Author "Reimer, Raylene A."
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- ItemOpen AccessCluster-specific associations between the gut microbiota and behavioral outcomes in preschool-aged children(2024-03-21) van de Wouw, Marcel; Wang, Yanan; Workentine, Matthew L.; Vaghef-Mehrabani, Elnaz; Barth, Delaney; Mercer, Emily M.; Dewey, Deborah; Arrieta, Marie-Claire; Reimer, Raylene A.; Tomfohr-Madsen, Lianne; Giesbrecht, Gerald F.Abstract Background The gut microbiota is recognized as a regulator of brain development and behavioral outcomes during childhood. Nonetheless, associations between the gut microbiota and behavior are often inconsistent among studies in humans, perhaps because many host-microbe relationships vary widely between individuals. This study aims to stratify children based on their gut microbiota composition (i.e., clusters) and to identify novel gut microbiome cluster-specific associations between the stool metabolomic pathways and child behavioral outcomes. Methods Stool samples were collected from a community sample of 248 typically developing children (3–5 years). The gut microbiota was analyzed using 16S sequencing while LC-MS/MS was used for untargeted metabolomics. Parent-reported behavioral outcomes (i.e., Adaptive Skills, Internalizing, Externalizing, Behavioral Symptoms, Developmental Social Disorders) were assessed using the Behavior Assessment System for Children (BASC-2). Children were grouped based on their gut microbiota composition using the Dirichlet multinomial method, after which differences in the metabolome and behavioral outcomes were investigated. Results Four different gut microbiota clusters were identified, where the cluster enriched in both Bacteroides and Bifidobacterium (Ba2) had the most distinct stool metabolome. The cluster characterized by high Bifidobacterium abundance (Bif), as well as cluster Ba2, were associated with lower Adaptive Skill scores and its subcomponent Social Skills. Cluster Ba2 also had significantly lower stool histidine to urocanate turnover, which in turn was associated with lower Social Skill scores in a cluster-dependent manner. Finally, cluster Ba2 had increased levels of compounds involved in Galactose metabolism (i.e., stachyose, raffinose, alpha-D-glucose), where alpha-D-glucose was associated with the Adaptive Skill subcomponent Daily Living scores (i.e., ability to perform basic everyday tasks) in a cluster-dependent manner. Conclusions These data show novel associations between the gut microbiota, its metabolites, and behavioral outcomes in typically developing preschool-aged children. Our results support the concept that cluster-based groupings could be used to develop more personalized interventions to support child behavioral outcomes. Video Abstract
- ItemOpen AccessDiet-induced obesity leads to pro-inflammatory alterations to the vitreous humour of the eye in a rat model(Springer Nature, 2018-02) Collins, Kelsey H.; Herzog, Walter; Reimer, Raylene A.; Reno, Carol R.; Heard, Bryan J.; Hart, David ArthurThe purpose of this study was to investigate if diet-induced obesity (DIO) and subsequent low-level systemic inflammation would result in local increases in pro-inflammatory mediators in the vitreous humour (VH) of the eyes of rats.
- ItemOpen AccessEarly life antibiotic and prebiotic exposure: impact on gut microbiota, metabolism and obesity risk(2019-09-18) Klančič, Teja; Reimer, Raylene A.; Pittman, Quentin J.; Shearer, JaneBackground: Obesity is a complex disease with multiple contributing factors including the gut microbiota. Antibiotics, when administered early in life, disrupt gut microbiota development and thereby increase the risk of obesity, whereas dietary agents such as prebiotics, reduce obesity risk via several pathways including microbiota-dependent mechanisms. Objective: This dissertation examines how antibiotics when administered with/without prebiotics, alter metabolic, microbial and anthropometric outcomes in rodents and humans. Specifically, the objectives were to: 1) assess the impact of indirect (maternal) antibiotic exposure with prebiotic co-administration on obesity risk in dams and their offspring; 2) determine the impact of direct antibiotic/prebiotic exposure in young rat pups on obesity risk and other metabolic parameters; 3) analyze available human birth cohort data from the All Our Families (AOF) study and explore the association between maternal antibiotic exposure and infant BMI z scores. Methods: 1) Sprague-Dawley rats consumed antibiotic and/or prebiotic during their 3rd week of pregnancy and lactation and their offspring were challenged with a high-fat high-sugar (HFS) diet from 9-17 weeks of age; 2) Rat pups were administered three pulses of azithromycin with/without prebiotic diet and weaned onto a HFS diet; 3) Using the AOF dataset, the association between infant BMI z score and maternal antibiotic use during pregnancy or during birth was examined. In the animal studies, body composition, gut microbiota composition, and metabolic outcomes were examined in dams and their offspring. In the human cohort, the association between antibiotic use during birth (intrapartum, n=1303)/during pregnancy (n=1943) and infant BMI z-score was investigated. Results: 1) Maternal antibiotic use during pregnancy/lactation impairs metabolism and postpartum weight loss in dams and increases obesity risk in their offspring, which was prevented with prebiotic co-administration; 2) Direct administration of azithromycin increased body weight and impaired insulin production/sensitivity. Prebiotic co-administration normalized the impairments; 3) Intrapartum antibiotic exposure might contribute to the development of child overweight/obesity at 1 year of age. Conclusion: Our results provide evidence for the ability of prebiotic co-administration with antibiotics to prevent metabolic impairments and obesity in rats. Future clinical trials should investigate whether this is also possible in humans.
- ItemOpen AccessEvaluation of yellow pea fibre supplementation on weight loss and the gut microbiota: a randomized controlled trial(BioMed Central, 2014-04-08) Lambert, Jennifer E.; Parnell, Jill A.; Han, Jay; Sturzenegger, Troy; Paul, Heather A.; Vogel, Hans J.; Reimer, Raylene A.
- ItemOpen AccessExercise and Dietary Interventions in a Rat Model of Cardiac Adaptation(2020-12-09) Boldt, Kevin; Herzog, Walter; Syme, Douglas A.; MacIntosh, Brian R.; Reimer, Raylene A.Cardiovascular disease is one of the leading causes of death and disability, and is responsible for approximately one third of all deaths. Conversely, effective functioning of the heart is critical for performance in many sports and recreational activities. Therefore, developing effective strategies for preventing cardiovascular disease and promoting enhanced function of the heart is paramount. The overarching purpose of this thesis was to evaluate how cardiac muscle develops and ways to improve its function through dietary and exercise intervention. The work of this thesis was conducted in three phases. In the first phase, we compared both the structural and mechanical adaptations of the heart in response to aerobic and resistance exercise training. We concluded that exercise affects the structure and function of the heart, and its cellular components in a manner that is specific to the exercise protocol, and that there may be additional benefit of combining aerobic and resistance exercise training. In the second phase, we evaluated the effects of systematic protein supplementation in addition to aerobic exercise on the structural and mechanical properties of the heart. We concluded from these findings that a whey supplemented high-protein diet did not provide additional benefit for cardiac adaptation following aerobic exercise. In the final phase, we compared contractile properties of the heart muscle over the first year of life in rats. We concluded from these findings that many of the previously observed changes in systolic function associated with aging, occur between 12 and 21-33 months of age, while early signs of increased diastolic stiffness manifest sooner. Overall, though more work is required, this thesis presents evidence that structural and mechanical properties of the heart are adaptable and can be modified by either positive (exercise and diet) or negative (obesity and aging) factors.
- ItemOpen AccessExercise and dietary interventions in a rat model of metabolic knee osteoarthritis(2019-09-05) Rios, Jaqueline Lourdes; Herzog, Walter; Hart, David D.; Reimer, Raylene A.; Krawetz, Roman J.; Beier, FrankOsteoarthritis is a debilitating chronic disease which has no cure or effective treatment. If no changes are made in prevention and treatment, osteoarthritis will continue to represent a significant economic burden to patients and society. The goal of this thesis was to determine the effects of moderate aerobic exercise and prebiotic fibre supplementation on the onset and progression of the metabolic knee osteoarthritis phenotype in rats exposed to a high-fat/high-sucrose diet. This study was divided into three phases. Phase 1: we evaluated the effects of a 12-week aerobic exercise program of varying duration on healthy rat knee cartilage. We determined that moderate, high and extra-high duration treadmill exercise has no detrimental effects on knee joint health, function and integrity. Therefore, we concluded that treadmill exercise at any tested duration was a safe exercise for rats in terms of knee osteoarthritis-like damage, and therefore, could be used as a safe exercise intervention in a pre-clinical rat model of knee osteoarthritis. Phase 2: we evaluated the effects of moderate aerobic exercise, prebiotic fibre supplementation, and the combination of exercise and fibre over a 12-week intervention in rats exposed to a high-fat/high-sucrose diet that has been shown to cause knee joint damage. Our findings indicated that prebiotic fibre and aerobic exercise prevented knee joint damage in this model. Phase 3: we evaluated if the damaging effects of the high-fat/high-sucrose diet could be delayed/reversed. We determined that neither prebiotic fibre supplementation nor aerobic exercise were able to stop the progression of existing knee osteoarthritis-like damage induced by a high-fat/high-sucrose diet. In summary, this thesis provides insight into two different approaches to prevent the development of metabolic osteoarthritis phenotype. However, the studies presented in this thesis were not able to show an effective way to stop the progression of the disease.
- ItemOpen AccessEXERCISE in pediatric autologous stem cell transplant patients: a randomized controlled trial protocol(BioMed Central, 2012-09-10) Khan, Faisal M.; Chamorro-Vina, Carolina; Culos-Reed, S. Nicole; Guilcher, Gregory M.T.; Mazil, Karen; Schulte, Fiona S. M.; Wurz, Amanda; Williamson, Tanya; Reimer, Raylene A.
- ItemOpen AccessGut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol(BMC Gastroenterology, 2015-12-03) Lambert, Jennifer E.; Parnell, Jill A.; Eksteen, Bertus; Raman, Maitreyi; Bomhof, Marc R.; Rioux, Kevin P.; Madsen, Karen L.; Reimer, Raylene A.Background Evidence for the role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is emerging. Strategies to manipulate the gut microbiota towards a healthier community structure are actively being investigated. Based on their ability to favorably modulate the gut microbiota, prebiotics may provide an inexpensive yet effective dietary treatment for NAFLD. Additionally, prebiotics have established benefits for glucose control and potentially weight control, both advantageous in managing fatty liver disease. Our objective is to evaluate the effects of prebiotic supplementation, adjunct to those achieved with diet-induced weight loss, on heptic injury and liver fat, the gut microbiota, inflammation, glucose tolerance, and satiety in patients with NAFLD. Methods/design In a double blind, placebo controlled, parallel group study, adults (BMI ≥25) with confirmed NAFLD will be randomized to either a 16 g/d prebiotic supplemented group or isocaloric placebo group for 24 weeks (n = 30/group). All participants will receive individualized dietary counseling sessions with a registered dietitian to achieve 10 % weight loss. Primary outcome measures include change in hepatic injury (fibrosis and inflammation) and liver fat. Secondary outcomes include change in body composition, appetite and dietary adherence, glycemic and insulinemic responses and inflammatory cytokines. Mechanisms related to prebiotic-induced changes in gut microbiota (shot-gun sequencing) and their metabolic by-products (volatile organic compounds) and de novo lipogenesis (using deuterium incorporation) will also be investigated. Discussion There are currently no medications or surgical procedures approved for the treatment of NAFLD and weight loss via lifestyle modification remains the cornerstone of current care recommendations. Given that prebiotics target multiple metabolic impairments associated with NAFLD, investigating their ability to modulate the gut microbiota and hepatic health in patients with NAFLD is warranted.
- ItemOpen AccessHigh-Fat High-Sucrose Diet Leads to Dynamic Structural and Inflammatory Alterations in the Rat Vastus Lateralis Muscle(Journal of Orthopaedic Research, 2016) Herzog, Walter; Collins, Kelsey; Hart, David A.; Reimer, Raylene A.; Seerattan, Ruth A.; Banker, Christine W.; Sibole, Scott C.The influence of obesity on muscle integrity is not well understood. The purpose of this study 37 was to quantify structural and molecular changes in the rat vastus lateralis (VL) muscle as a 38 function of a 12-week obesity induction period and a subsequent adaptation period (additional 39 16-weeks). Male Sprague-Dawley rats consumed a high-fat, high-sucrose (DIO, n=40) diet or a 40 chow control-diet (n=14). At 12-weeks, DIO rats were grouped as prone (DIO-P, top 33% of 41 weight change) or resistant (DIO-R, bottom 33%). Animals were euthanized at 12-weeks or 28-42 weeks on the diet. At sacrifice, body composition was determined and VL muscles were 43 collected. Intramuscular fat, fibrosis, and CD68+ cells were quantified histologically and 44 relevant molecular markers were evaluated using RT-qPCR. At 12- and 28-weeks post obesity 45 induction, DIO-P rats had more mass and body fat than DIO-R and chow rats (p<0.05). DIO-P 46 and DIO-R rats had similar losses in muscle mass, which were greater than those in chow rats 47 (p<0.05). mRNA levels for MAFbx/atrogin1 were reduced in DIO-P and DIO-R rats at 12- and 48 28-weeks compared to chow rats (p<0.05), while expression of MURF was similar to chow 49 values. DIO-P rats demonstrated increased mRNA levels for pro-inflammatory mediators, 50 inflammatory cells, and fibrosis compared to DIO-R and chow animals, despite having similar 51 levels of intramuscular fat. The down-regulation of MAFbx/atrogin1 may suggest onset of 52 degenerative changes in VL muscle integrity of obese rats. DIO-R animals exhibited fewer 53 inflammatory changes compared to DIO-P animals, suggesting a protective effect of obesity 54 resistance on local inflammation.
- ItemOpen AccessImpact of a farmers’ market healthy food subsidy on the diet quality of adults with low incomes in British Columbia, Canada: a pragmatic randomized controlled trial(Elsevier, 2023-02-01) Aktary, Michelle L.; Dunn, Sharlette; Sajobi, Tolulope; O'Hara, Heather; Leblanc, Peter; McCormack, Gavin R.; Caron-Roy, Stephanie; Ball, Kylie; Lee, Yun Yun; Nejatinamini, Sara; Reimer, Raylene A.; Pan, Bo; Minaker, Leia M.; Raine, Kim D.; Godley, Jenny; Downs, Shauna; Nykiforuk, Candace I.J.; Olstad, Dana LeeAdults with low incomes have lower diet quality than their higher income counterparts. In Canada, the British Columbia Farmers’ Market Nutrition Coupon Program (FMNCP) provides coupons to low-income households to purchase healthy foods in farmers’ markets.
- ItemOpen AccessImpact of Alterations to Early Life Microbiota (Antibiotics, Prebiotics, and C-Section) on Body Weight and Brain Development(2021-09-21) Cho, Nicole A; Reimer, Raylene A.; Mychasiuk, Richelle; Sharkey, Keith A; Giesbrecht, GeraldBackground: Communication between the gut microbiota, gut, and brain is now known to influence behavior, metabolic health, and immunity. Foods that improve the composition of the gut microbiota as well as factors that can disrupt it during early development are of interest to investigate the origins of and possible therapeutics for chronic diseases like obesity and mood and neurodevelopmental disorders. Objective: This dissertation examines how early life perturbations to gut microbiota, such as maternal antibiotic use, prebiotic consumption, maternal obesity, and C-section (CS) alter microbial, metabolic, behavioral, and brain outcomes. Specifically, the objectives of this thesis were to: 1) assess the impact of CS in offspring of lean and obese dams on offspring obesity risk; 2) examine the impact of CS and maternal prebiotic intake on offspring microglia and neuron morphology; 3) determine the effects of maternal antibiotic/prebiotic intake on offspring behavior and microglia reactivity; 4) investigate the effects of maternal and child antibiotic use on BMI z-score and temperament in 3-year-old children in a clinical cohort.Methods: Animal studies were conducted in Sprague-Dawley rats or NIH Swiss mice. Clinical participant data was accessed from the Alberta Pregnancy and Nutrition Outcomes (APrON) study. Body composition was measured with dual x-ray absorptiometry (DXA). Elevated Plus Maze (EPM), Novel Context Mismatch (NCM), and Sucrose Preference Tests (SPT) were used to assess behavior. Microglia were analyzed using the expression of IBA-1. Gut microbiota was assessed using 16S rRNA gene sequencing, and tissue gene expression was measured using RT-PCR. Temperament data was assessed using the Child Behavior Questionnaire (CBQ).Results: The primary findings from our study objectives were: 1) CS-associated obesity risk in offspring is dependent on maternal obesity status; 2) Maternal prebiotic intake reverses CS-induced alterations to microglia; 3) Antibiotic-induced alterations to microglia are reversed by maternal prebiotic intake; 4) Maternal and child antibiotic use is associated with increased BMI z-score in children. Conclusion: Our results provide evidence that early-life microbial perturbations alter obesity risk and microglia activation. We also demonstrated the potential for prebiotics to reduce the neuroinflammation that could modulate the risk for mood and neuropsychiatric disorders.
- ItemOpen AccessLeptin Deficiency and Its Effects on Tibial and Vertebral Bone Mechanical Properties in Mature Genetically Lean and Obese JCR:LA-Corpulent Rats(2012-07-19) Reimer, Raylene A.; LaMothe, Jeremy M.; Zernicke, Ronald F.Leptin signaling deficient rodents have emerged as models of obesity/insulin resistance syndrome. Altered leptin signaling, however, can affect axial and appendicular bone geometrical properties differently, and, thus, we hypothesized that leptin-deficiency would differentially influence mechanical properties of vertebrae and tibiae compared to lean rats. Mature (9 mo) leptin receptor deficient obese (cp/cp; n=8) and lean (+/?; n=7) male JCR:LA-corpulent rats were used to test that hypothesis. Tibiae and the sixth lumbar vertebrae (L6) were scanned with micro-CT and were broken in three point-bending (tibiae) or axial loading (L6). Supporting the hypothesis, vertebrae and tibiae were differentially affected by leptin signaling deficiency. Tibiae, but not vertebrae, were significantly shorter in obese rats and achieved a significantly greater load (>18%), displacement (>15%), and stress (>18%) at the proportional limit, relative to the lean rats. Conversely, L6 in obese rats had significantly reduced displacement (>25%) and strain (>32%) at proportional limit, relative to the lean rats. Those combined results suggest that the etiology and duration of obesity may be important determinants of bone mechanical properties, and axial and appendicular bones may be affected differently.
- ItemOpen AccessThe mechanical and biochemical properties of tail tendon in a rat model of obesity: effect of moderate exercise and prebiotic fibre supplementation(2019-05-09) Rios, Jaqueline Lourdes; Ko, Loretta; Joumaa, Venus; Liu, Shuyue; Diefenthaeler, Fernando; Sawatsky, Andrew; Hart, David A.; Reimer, Raylene A.; Herzog, WalterThe worldwide trajectory of increasing obesity rates is a major health problem precipitating a rise in the prevalence of a variety of co-morbidities and chronic diseases. Tendinopathy, in weight and non-weight bearing tendons, in individuals with overweight or obesity has been linked to metabolic dysfunction resulting from obesity. Exercise and dietary fibre supplementation (DFS) are common countermeasures to combat obesity and therefore it seems reasonable to assume that they might protect tendons from structural and mechanical damage in a diet-induced obesity (DIO) model. The purpose of this study was to determine the effects of a DIO, DIO combined with moderate exercise, DIO combined with DFS (prebiotic oligofructose), and DIO combined with moderate exercise and DFS on the mechanical and biochemical properties of the rat tail tendon. Twenty-four male Sprague-Dawley rats, fed a high-fat/high-sucrose diet were randomized into a sedentary, a moderate exercise, a DFS, or a moderate exercise combined with DFS group for 12 weeks. Additionally, six lean age-matched animals were included as a sedentary control group. DIO in combination with exercise alone and with exercise and DFS reduced the Young's Modulus but not the collagen content of the rat tail tendons compared to lean control animals. However, no differences in the mechanical and biochemical properties of the rat tail tendon were detected between the DIO and the lean control group, suggesting that DIO by itself did not impact the tail tendon. It seems that longer DIO exposure periods may be needed to develop overt differences in our DIO model.
- ItemOpen AccessProtective effect of prebiotic and exercise intervention on knee health in a rat model of diet-induced obesity(2019-03-07) Rios, Jaqueline Lourdes; Bomhof, Marc R.; Reimer, Raylene A.; Hart, David A.; Collins, Kelsey H.; Herzog, WalterObesity, and associated metabolic syndrome, have been identified as primary risk factors for the development of knee osteoarthritis (OA), representing nearly 60% of the OA patient population. In this study, we sought to determine the effects of prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions, on the development of metabolic knee osteoarthritis in a high-fat/high-sucrose (HFS) diet-induced rat model of obesity. Twelve-week-old male Sprague-Dawley rats were randomized into five groups: a non-exercising control group fed a standard chow diet, a non-exercising group fed a HFS diet, a non-exercising group fed a HFS diet combined with prebiotic fibre supplement, an exercise group fed a HFS diet, and an exercise group fed a HFS diet combined with prebiotic fibre supplement. Outcome measures included knee joint damage, percent body fat, insulin sensitivity, serum lipid profile, serum endotoxin, serum and synovial fluid cytokines and adipokines, and cecal microbiota. Prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions completely prevented knee joint damage that is otherwise observed in this rat model of obesity. Prevention of knee damage was associated with a normalization of insulin resistance, leptin levels, dyslipidemia, gut microbiota, and endotoxemia in the HFS-fed rats.
- ItemOpen AccessResponse to Diet-Induced Obesity Produces Time-dependent Induction and Progression of Metabolic Osteoarthritis in Rat Knees(Journal of Orthopaedic Research, 2016) Herzog, Walter; Collins, Kelsey; Hart, David A,; Reimer, Raylene A.; Seerattan, Ruth A.Obesity, and corresponding chronic-low grade inflammation, is associated with the onset and progression of knee OA. The origin of this inflammation is poorly understood. Here, the effect of high fat, high sucrose (HFS) diet induced obesity (DIO) on local (synovial fluid) and systemic (serum) inflammation is evaluated after a 12-week obesity induction and a further 16-week adaptation period. For 12-weeks of obesity induction, n=40 DIO male Sprague-Dawley rats consumed a HFS diet while the control group (n=14) remained on chow. DIO rats were allocated to prone (DIO-P, top 33% based on weight change) or resistant (DIO-R, bottom 33%) groups at 12-weeks. Animals were euthanized at 12- and after an additional 16-weeks on diet (28-weeks). At sacrifice, body composition and knee joints were collected and assessed. Synovial fluid and sera were profiled using cytokine array analysis. At 12-weeks, DIO-P animals demonstrated increased Modified Mankin Scores compared to DIO-R and Chow (p=0.026), and DIO-R had higher Mankin scores compared to Chow (p=0.049). While numerous systemic and limited synovial fluid inflammatory markers were increased at 12-weeks in DIO animals compared to Chow, by 28-weeks there were limited systemic differences but marked increases in local synovial fluid inflammatory marker concentrations. Metabolic OA may manifest from an initial systemic inflammatory disturbance. 12-weeks of obesity induction leads to a unique inflammatory profile and induction of metabolic OA which is altered after a further 16-weeks of obesity and HFS diet intake, suggesting that obesity is a dynamic, progressive process.
- ItemOpen AccessThe use of near-infrared spectroscopy for microvascular function assessment in healthy and with obesity individuals during normo- and hyperglycemia(2019-09-19) Nogueira Soares, Rogerio; Murias, Juan M.; Doyle-Baker, Patricia K.; Reimer, Raylene A.; Fletcher, Jared R.; MacDonald, Maureen JaneVascular function has been shown to be an important predictor for cardiovascular disease (CVD). Among others, postprandial hyperglycemia has been shown to be a risk factor for CVD that is associated with impaired vascular function. Among others, obesity is a comorbidity associated with vascular dysfunction. In addition to the detrimental effects of obesity per se on the vasculature, obesity is also linked to impairments in glucose uptake/metabolism by the skeletal muscle, which further expose these individuals to the deleterious effects of glucose on the vascular tree. Thus, the overall objectives of the current thesis were to: i) assess changes in lower limb microvascular responsiveness induced by hyperglycemia in lean and obese individuals by using the near-infrared spectroscopy (NIRS) combined with vascular occlusion test (VOT) technique (NIRS-VOT); ii) use NIRS-VOT to compare differences in lower limb microvascular responsiveness during normoglycemia and hyperglycemia in lean and obese individuals; iii) investigate upper and lower limbs microvascular function and oxidative metabolism responses to glucose ingestion in participants with obesity compared to their healthy lean counterparts; iv) investigate the relationship between changes in upstream brachial artery flow-mediated dilation (FMD) and NIRS-VOT-derived assessment of forearm microvascular function induced by glucose ingestion in these individuals. The main findings of the present thesis were that NIRS-VOT detected hyperglycemia and obesity-related differences in microvascular responsiveness. Additionally, although no differences in the forearm microvascular responses to glucose ingestion were found between these two groups, obese individuals had impaired brachial FMD during hyperglycemia. The findings also demonstrated a blunted leg muscle oxidative metabolism response to glucose ingestion in obese individuals. The current thesis highlights the importance of assessing limb and muscle specific effects of hyperglycemia and obesity.