Publications by authors named "Roeland J W Middelbeek"

Beta (β)-cell senescence contributes to type 2 diabetes mellitus (T2DM). While exercise is vital for T2DM management and significantly affects cellular ageing markers, its effect on β-cell senescence remains unexplored. Here, we show that short-term endurance exercise training (treadmill running, 1 h per day for 10 days) in two male and female mouse models of insulin resistance decreases β-cell senescence.

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Exercise training and cold exposure both improve systemic metabolism, but the mechanisms are not well established. Here, we tested the hypothesis that inguinal white adipose tissue (iWAT) adaptations are critical for these beneficial effects and determined the impact of exercise-trained and cold-exposed iWAT on systemic glucose metabolism and the iWAT proteome and secretome. Transplanting trained iWAT into sedentary mice improves glucose tolerance, while cold-exposed iWAT transplantation shows no such benefit.

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Exercise training and cold exposure both improve systemic metabolism, but the mechanisms are not well-established. We tested the hypothesis that adaptations to inguinal white adipose tissue (iWAT) are critical for these beneficial effects by determining the impact of exercise-trained and cold-exposed iWAT on systemic glucose metabolism and the iWAT proteome and secretome. Transplanting trained iWAT into sedentary mice improved glucose tolerance, while cold-exposed iWAT transplantation showed no such benefit.

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Physical activity is important for type 2 diabetes treatment, yet the underlying mechanisms for these beneficial effects of exercise are not fully understood. Here, we investigated the effects of exercise training on biphasic β-cell insulin secretory function, a key factor regulating blood glucose. Adults with type 2 diabetes (7F/3M, age 49 ± 5 years, BMI 30 ± 3 kg/m) completed a 10-week moderate-intensity exercise program and multiple components of glucose homeostasis were measured.

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Objective: We aimed to determine the association of the time-of-day of bout-related moderate-to-vigorous physical activity (bMVPA) with changes in glycemic control across 4 years in adults with overweight/obesity and type 2 diabetes.

Research Design And Methods: Among 2,416 participants (57% women; mean age, 59 years) with 7-day waist-worn accelerometry recording at year 1 or 4, we assigned bMVPA timing groups based on the participants' temporal distribution of bMVPA at year 1 and recategorized them at year 4. The time-varying exposure of bMVPA (≥10-min bout) timing was defined as ≥50% of bMVPA occurring during the same time period (morning, midday, afternoon, or evening), <50% of bMVPA in any time period (mixed), and ≤1 day with bMVPA per week (inactive).

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Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood, and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses, we find that 11 days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition and increased vascularization and innervation.

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Exercise training is critical for the prevention and treatment of obesity, but its underlying mechanisms remain incompletely understood given the challenge of profiling heterogeneous effects across multiple tissues and cell types. Here, we address this challenge and opposing effects of exercise and high-fat diet (HFD)-induced obesity at single-cell resolution in subcutaneous and visceral white adipose tissue and skeletal muscle in mice with diet and exercise training interventions. We identify a prominent role of mesenchymal stem cells (MSCs) in obesity and exercise-induced tissue adaptation.

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The COVID-19 pandemic has stimulated a rapid shift towards telemedicine, which has had tremendous repercussions on all domains of the healthcare ecosystem. The effects of the transition to telemedicine on post-graduate medical education and on patient care provided by trainees have not been fully elucidated. Focusing on the multifaceted scope of endocrinology teaching clinics, the experience garnered by endocrinology fellows, preceptors, and patients through the adoption of virtual visits has shed new light on relevant challenges that require specific attention.

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Purpose: Obesity and type 2 diabetes are associated with an increased risk of cardiovascular disease (CVD) and the combination of weight loss and increased physical exercise are commonly recommended to reduce CVD. This study examined whether people with obesity and type 2 diabetes with an abnormal graded exercise tolerance test (GXT) or a history of CVD would have less success in achieving weight loss and improved fitness, compared to adults without these conditions.

Methods: The Look AHEAD Study examined whether an intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) reduced cardiovascular events in adults with overweight/obesity and type 2 diabetes.

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Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance.

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Objective: Moderate- to vigorous-intensity physical activity (MVPA) improves cardiovascular health. Few studies have examined MVPA timing. We examined the associations of timing of bout-related MVPA with cardiorespiratory fitness and cardiovascular risk in adults with type 2 diabetes.

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Recent studies demonstrate that adaptations to white adipose tissue (WAT) are important components of the beneficial effects of exercise training on metabolic health. Exercise training favorably alters the phenotype of subcutaneous inguinal WAT (iWAT) in male mice, including decreasing fat mass, improving mitochondrial function, inducing beiging, and stimulating the secretion of adipokines. In this study, we find that despite performing more voluntary wheel running compared with males, these adaptations do not occur in the iWAT of female mice.

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Background: Short-term exercise training programs that consist of moderate intensity endurance training or high intensity interval training have become popular choices for healthy lifestyle modifications, with as little as two weeks of training being shown to improve cardiorespiratory fitness and whole-body glucose metabolism. An emerging concept in exercise biology is that exercise stimulates the release of cytokines and other factors into the blood that contribute to the beneficial effects of exercise on metabolism, but whether these factors behave similarly in response to moderate and high intensity short term training is not known. Here, we determined the effects of two short-term exercise training programs on the concentrations of select secreted cytokines and Klotho, a protein involved in anti-aging.

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Background: To examine the relationship between early physical activity (PA) adoption (2, 3, and 4 mo) and longer-term PA adherence (1 y) among individuals who were inactive at baseline and received a lifestyle intervention.

Methods: Participants (n = 637) received weekly behavioral weight loss sessions, calorie reduction, and PA goals (50-175 min/wk progression). PA was assessed via self-reported measures at baseline, months 2 to 4, and 1 year.

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Exercise improves health and well-being across diverse organ systems, and elucidating mechanisms underlying the beneficial effects of exercise can lead to new therapies. Here, we show that transforming growth factor-β2 (TGF-β2) is secreted from adipose tissue in response to exercise and improves glucose tolerance in mice. We identify TGF-β2 as an exercise-induced adipokine in a gene expression analysis of human subcutaneous adipose tissue biopsies after exercise training.

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Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects.

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Context: The presence of differentiated thyroid cancer in mature cystic teratomas in the ovaries is rare, and usually incidentally found on surgical pathology specimens. We present a case of simultaneous intrathyroidal thyroid cancer and thyroid cancer within a struma ovarii, presenting specific diagnostic challenges.

Case Description: A 55-year-old woman had an intrathyroidal, encapsulated 1.

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Bariatric surgery is increasingly recognized as one of the most effective interventions to help patients achieve significant and sustained weight loss, as well as improved metabolic and overall health. Unfortunately, the cellular and physiological mechanisms by which bariatric surgery achieves weight loss have not been fully elucidated, yet are critical to understanding the central role of the intestinal tract in whole-body metabolism and to developing novel strategies for the treatment of obesity. In this review, we provide an overview of potential mechanisms contributing to weight loss, including effects on regulation of energy balance and both central and peripheral nervous system regulation of appetite and metabolism.

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Regular physical activity and exercise training have long been known to cause adaptations to white adipose tissue (WAT), including decreases in cell size and lipid content and increases in mitochondrial proteins. In this article, we discuss recent studies that have investigated the effects of exercise training on mitochondrial function, the "beiging" of WAT, regulation of adipokines, metabolic effects of trained adipose tissue on systemic metabolism, and depot-specific responses to exercise training. The major WAT depots in the body are found in the visceral cavity (vWAT) and subcutaneously (scWAT).

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