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- Rodrigues Silva, Vagner Ramon, 1985, et al.
(författare)
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Somatic ablation of IKKβ in liver and leukocytes is not tolerated in obese mice but hepatic IKKβ deletion improves fatty liver and insulin sensitivity.
- 2022
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Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - 1530-6860. ; 36:9
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Tidskriftsartikel (refereegranskat)abstract
- The kinase IKKβ controls pro-inflammatory gene expression, and its activity in the liver and leukocytes was shown to drive metabolic inflammation and insulin resistance in obesity. However, it was also proposed that liver IKKβ signaling protects obese mice from insulin resistance and endoplasmic reticulum (ER) stress by increasing XBP1s protein stability. Furthermore, mice lacking IKKβ in leukocytes display increased lethality to lipopolysaccharides. This study aims at improving our understanding of the role of IKKβ signaling in obesity. We induced IKKβ deletion in hematopoietic cells and liver of obese mice by Cre-LoxP recombination, using an INF-inducible system, or a liver-specific IKKβ deletion in obese mice by adenovirus delivery of the Cre recombinase. The histopathological, immune, and metabolic phenotype of the mice was characterized. IKKβ deletion in the liver and hematopoietic cells was not tolerated in mice with established obesity exposed to the TLR3 agonist poly(I:C) and exacerbated liver damage and ER-stress despite elevated XBP1s. By contrast, liver-specific ablation of IKKβ in obese mice reduced steatosis and improved insulin sensitivity in association with increased XBP1s protein abundance and reduced expression of de-novo lipogenesis genes. We conclude that IKKβ blockage in liver and leukocytes is not tolerated in obese mice exposed to TLR3 agonists. However, selective hepatic IKKβ ablation improves fatty liver and insulin sensitivity in association with increased XBP1s protein abundance and reduced expression of lipogenic genes.
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| 2. |
- Arvidsson, Daniel, 1974, et al.
(författare)
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Cardiorespiratory fitness and the association with galectin-1 in middle-aged individuals.
- 2024
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:4
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-1 plays a functional role in human metabolism and the levels are altered in obesity and type 2 diabetes (T2D). This study investigates the association of cardiorespiratory fitness (CRF) with galectin-1 and the interconnection with body fatness. Cross-sectional data from the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot was analyzed, including a sample of 774 middle-aged individuals. A submaximal cycle ergometer test was used to estimate CRF as an indirect measure of the physical activity (PA) level. Serum-galectin-1 concentration was determined from venous blood collected after an overnight fast. Body mass index (BMI) was used as an indirect measure of body fatness. CRF was significantly associated with galectin-1, when controlled for age and sex (regression coefficient (regr coeff) = -0.29, p<0.001). The strength of the association was attenuated when BMI was added to the regression model (regr coeff = -0.09, p = 0.07), while the association between BMI and galectin-1 remained strong (regr coeff = 0.40, p<0.001). CRF was associated with BMI (regr coeff = -0.50, p<0.001). The indirect association between CRF and galectin-1 through BMI (-0.50 x 0.40) contributed to 69% of total association (mediation analysis). In group comparisons, individuals with low CRF-high BMI had the highest mean galectin-1 level (25 ng/ml), while individuals with high CRF-low BMI had the lowest level (21 ng/ml). Intermediate levels of galectin-1 were found in the low CRF-low BMI and high CRF-high BMI groups (both 22 ng/ml). The galectin-1 level in the low CRF-high BMI group was significantly different from the other three groups (P<0.001). In conclusion, galectin-1 is associated with CRF as an indirect measure of the PA level through interconnection with body fatness. The size of the association is of clinical relevance.
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| 3. |
- Belozo, Felipe L., et al.
(författare)
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Anterior cruciate ligament: A brief narrative review of main risk factors for injury and re-injury
- 2024
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Ingår i: JOURNAL OF BODYWORK AND MOVEMENT THERAPIES. - 1360-8592 .- 1532-9283. ; 38, s. 92-99
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Tidskriftsartikel (refereegranskat)abstract
- Anterior cruciate ligament (ACL) injury is one of the main injuries in professional and amateur athletes of different sports. Hundreds of thousands of ACL ruptures occurs annually, and only 55% of the athletes return to competitive level, with a 15 times higher chance of suffering a second injury. 60% of these injuries occur without physical contact and since they occur in the acute process, they can cause joint effusion, muscle weakness and functional incapacity. In the long term, they can contribute to a premature process of osteoarthritis. This narrative review is of particular interest for clinicians, practitioners, coaches and athletes to understand the main factors that contribute to an injury and/or re-injury and thus, to optimize their training to reduce and/or prevent the risk of injury and/or reinjury of ACL. Therefore, we aimed reports a narrative overview of the literature surrounding communication and explore through a theoretical review, the main risk factors for an ACL injury and/or re-injury, as well as bringing practical and correct methods of training applications. The lack of theoretical/practical knowledge on the part of rehabilitation and/or training professionals may impair the treatment of an athlete and/or student. High-quality research that can testing different training methods approaches in randomized controlled trials is needed.
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| 4. |
- Fryk, Emanuel, et al.
(författare)
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Feasibility of high-dose tadalafil and effects on insulin resistance in well-controlled patients with type 2 diabetes (MAKROTAD): a single-centre, double-blind, randomised, placebo-controlled, cross-over phase 2 trial
- 2023
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Ingår i: Eclinicalmedicine. ; 59
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Tidskriftsartikel (refereegranskat)abstract
- Background Phosphodiesterase-5 inhibitors exert positive vascular and metabolic effects in type 2 diabetes (T2D), but the effect on insulin resistance in T2D is unclear. Methods This randomised, double blind, placebo-controlled, two-period crossover trial was conducted at Sahlgrenska University Hospital (Gothenburg, Sweden). Men without apparent erectile dysfunction (age 40-70 years) and women (age 55-70 years, post-menopause) diagnosed with T2D between 3 months and 10 years, haemoglobin A1c (HbA1c) < 60 mmol/mol and a body mass index (BMI) 27-40 kg/m2 were enrolled. Participants were randomly assigned to one period of oral tadalafil 20 mg once a day and one period of placebo for 6 weeks, separated by an 8-week wash-out period. Placebo and tadalafil tablets were made visually indistinguishable and delivered randomized in two separate boxes for each participant. Both treatment periods ended with a glucose clamp, and measurements of body composition and metabolic markers in blood, subcutaneous and muscular interstitial fluid. The primary aim was to assess difference in whole-body insulin resistance after 6-weeks of treatment, determined after completion of the two study arms, and secondary aims were to study effects of tadalafil on pathophysiology of T2D as well as tolerability of high-dose tadalafil in T2D. Primary analysis was performed in participants with full analysis set (FAS) and safety analysis in all participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT02601989), and EudraCT (2015-000573). Findings Between January 22nd, 2016, and January 31st, 2019, 23 participants with T2D were enrolled, of whom 18 were included in the full analysis set. The effect of tadalafil on insulin resistance was neutral compared with placebo. However, tadalafil decreased glycaemia measured as HbA1c (mean difference -2.50 mmol/mol, 95% confidence interval (CI), -4.20; -0.78, p = 0.005), and, further, we observed amelioration of endothelial function and markers of liver steatosis and glycolysis, whereas no statistically significant differences of other clinical phenotyping were shown. Muscle pain, dyspepsia, and headache were more frequent in participants on high-dose tadalafil compared with placebo (p < 0.05) but no difference between treatments appeared for serious adverse events. Interpretation High-dose tadalafil does not decrease whole-body insulin resistance, but increases microcirculation, induces positive effects in the liver and in intermediate metabolites, in parallel with an improved metabolic control measured as HbA1c. High-dose tadalafil is moderately well tolerated, warranting larger trials to define the optimal treatment regimen in T2D.
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| 5. |
- Fryk, Emanuel, et al.
(författare)
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Galectin-1 in Obesity and Type 2 Diabetes
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-1 is a carbohydrate-binding protein expressed in many tissues. In recent years, increasing evidence has emerged for the role of galectin-1 in obesity, insulin resistance and type 2 diabetes. Galectin-1 has been highly conserved through evolution and is involved in key cellular functions such as tissue maturation and homeostasis. It has been shown that galectin-1 increases in obesity, both in the circulation and in the adipose tissue of human and animal models. Several proteomic studies have independently identified an increased galectin-1 expression in the adipose tissue in obesity and in insulin resistance. Large population-based cohorts have demonstrated associations for circulating galectin-1 and markers of insulin resistance and incident type 2 diabetes. Furthermore, galectin-1 is associated with key metabolic pathways including glucose and lipid metabolism, as well as insulin signalling and inflammation. Intervention studies in animal models alter animal weight and metabolic profile. Several studies have also linked galectin-1 to the progression of complications in diabetes, including kidney disease and retinopathy. Here, we review the current knowledge on the clinical potential of galectin-1 in obesity and type 2 diabetes.
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| 6. |
- Yamada, A. K., et al.
(författare)
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Effect of caffeine on mitochondrial biogenesis in the skeletal muscle – A narrative review
- 2022
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 51, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Caffeine is one of the most widely used substances as recreational drug for performance-enhancement in sport, underpinned by a strong evidence base. Although the effects of caffeine are widely investigated within the scope of performance physiology, the molecular effects of caffeine within skeletal muscle remain unclear. Evidence from in vitro and in vivo models suggest that caffeine regulates the glucose metabolism in the skeletal muscle. Moreover, caffeine seems to stimulate CaMKII, PPARδ/β, AMPK and PGC1α, classical markers of exercise-adaptations, including mitochondrial biogenesis and mitochondrial content. This review summarizes evidence to suggest caffeine-effects within skeletal muscle fibers, focusing on the putative role of caffeine on mitochondrial biogenesis to explore whether caffeine supplementation might be a strategy to enhance mitochondrial biogenesis. © 2022 The Author(s)
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