| 1. |
- Pham, T. T., et al.
(författare)
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Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot
- 2020
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:7, s. 2300-2310
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Bone marrow (BM) in adult long bones is rich in adipose tissue, but the functions of BM adipocytes are largely unknown. We set out to elucidate the metabolic and molecular characteristics of BM adipose tissue (BMAT) in humans. OBJECTIVE: Our aim was to determine if BMAT is an insulin-sensitive tissue, and whether the insulin sensitivity is altered in obesity or type 2 diabetes (T2DM). DESIGN: This was a cross-sectional and longitudinal study. SETTING: The study was conducted in a clinical research center. PATIENTS OR OTHER PARTICIPANTS: Bone marrow adipose tissue glucose uptake (GU) was assessed in 23 morbidly obese subjects (9 with T2DM) and 9 healthy controls with normal body weight. In addition, GU was assessed in another 11 controls during cold exposure. Bone marrow adipose tissue samples for molecular analyses were collected from non-DM patients undergoing knee arthroplasty. INTERVENTION(S): Obese subjects were assessed before and 6 months after bariatric surgery and controls at 1 time point. MAIN OUTCOME MEASURE: We used positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose tracer to characterize GU in femoral and vertebral BMAT. Bone marrow adipose tissue molecular profile was assessed using quantitative RT-PCR. RESULTS: Insulin enhances GU in human BMAT. Femoral BMAT insulin sensitivity was impaired in obese patients with T2DM compared to controls, but it improved after bariatric surgery. Furthermore, gene expression analysis revealed that BMAT was distinct from brown and white adipose tissue. CONCLUSIONS: Bone marrow adipose tissue is a metabolically active, insulin-sensitive and molecularly distinct fat depot that may play a role in whole body energy metabolism. © Endocrine Society 2020.
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| 2. |
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| 3. |
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| 4. |
- Koffert, J. P., et al.
(författare)
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Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial
- 2017
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 131, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- Aims Metformin therapy is associated with diffuse intestinal 18F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats. Methods Forty-one patients with newly diagnosed type 2 diabetes were randomized to metformin (1g, b.i.d), rosiglitazone (4mg, b.i.d), or placebo in a 26-week double-blind trial. Tissue specific intestinal glucose uptake was measured before and after the treatment period using FDG-PET during euglycemic hyperinsulinemia. In addition, rats were treated with metformin or vehicle for 12weeks, and intestinal FDG uptake was measured in vivo and with autoradiography. Results Glucose uptake increased 2-fold in the small intestine and 3-fold in the colon for the metformin group and associated with improved glycemic control. Rosiglitazone increased only slightly intestinal glucose uptake. In rodents, metformin treatment enhanced intestinal FDG retention (P=0.002), which was localized in the mucosal enterocytes of the small intestine. Conclusions Metformin treatment significantly enhances intestinal glucose uptake from the circulation of patients with type 2 diabetes. This intestine-specific effect is associated with improved glycemic control and localized to mucosal layer. These human findings demonstrate directs effect of metformin on intestinal metabolism and elucidate the actions of metformin. Clinical trial number NCT02526615 © 2017 The Authors
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| 5. |
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| 6. |
- Kalliokoski, K.K, et al.
(författare)
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Muscle fractal vascular branching pattern and microvascular perfusion heterogeneity in endurance-trained and untrained men
- 2003
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Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 546:pt2, s. 529-35
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Tidskriftsartikel (refereegranskat)abstract
- Less heterogeneous skeletal muscle perfusion has recently been reported in endurance-trained compared to untrained men at macrovascular level. The causes of this difference in perfusion heterogeneity are unknown as is whether the same difference is observed in microvasculature. We hypothesised that the difference could be caused by changes in muscle vascular branching pattern. Perfusion was measured in resting and exercising muscle in 14 endurance-trained and seven untrained men using [(15)O]water and positron emission tomography. Fractal dimension (D) of perfusion distribution was calculated as a measure of fractal characteristics of muscle vascular branching pattern. Perfusion heterogeneity in microvascular units (1 mm(3) samples) was estimated using the measured heterogeneity in voxels of positron emission tomography (PET) images (relative dispersion, RD = S.D./mean) and corresponding D values. D was similar between the groups (exercising muscle 1.11 +/- 0.07 and 1.14 +/- 0.06, resting muscle 1.12 +/- 0.06 and 1.14 +/- 0.03, trained and untrained, respectively). Trained men had lower perfusion (151 +/- 44 vs. 218 +/- 87 ml min(-1) kg(-1), P < 0.05) and macrovascular perfusion heterogeneity (relative dispersion 21 +/- 5 vs. 25 +/- 5 %, P < 0.05) in exercising muscle than untrained men. Furthermore, estimated perfusion heterogeneity in microvascular units in exercising muscle was also lower in trained men (33 +/- 7 vs.48 +/- 19 %, P < 0.05). These results show that fractal vascular branching pattern is similar in endurance-trained and untrained men but perfusion is less heterogeneous at both the macro- and the microvascular level in endurance-trained men. Thus, changes in fractal branching pattern do not explain the differences in perfusion heterogeneity between endurance-trained and untrained men.
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| 7. |
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| 8. |
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| 9. |
- Kalliokoski, K K, et al.
(författare)
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Perfusion distribution between and within muscles during intermittent static exercise in endurance-trained and untrained men
- 2003
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Ingår i: International Journal of Sports Medicine. - : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 24, s. 400-403
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Tidskriftsartikel (refereegranskat)abstract
- We have recently shown that muscle perfusion varies between different quadriceps femoris muscles during submaximal exercise in humans. In animals, endurance training changes perfusion distribution between muscles during exercise. Whether the same is observed in humans is currently unknown. Therefore, we compared perfusion levels between different parts of the quadriceps femoris muscle group during one-legged intermittent static exercise in seven endurance-trained and seven untrained men. Muscle perfusion was measured using positron emission tomography with [ 15O]-H 2 O. In addition, relative dispersion of perfusion (standard deviation within a region/mean within a region x 100 %) within each muscle region was calculated as an index of perfusion heterogeneity within the muscles. Muscle perfusion tended to be lower in endurance-trained men (p = 0.16) and it was also different between the regions (p < 0.001). However, perfusion distributed similarly between the groups (p = 0.51). Relative dispersion of perfusion within the muscles was lower in endurance-trained men (p = 0.01) and it was also different between muscles (p < 0.001). These results suggest that endurance training does not alter perfusion distribution between muscles, but it decreases perfusion heterogeneity within the muscles.
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| 10. |
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| 11. |
- Laaksonen, Marko, et al.
(författare)
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Effects of exhaustive stretch-shortening cycle exercise on muscle blood flow during exercise
- 2006
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 186:4, s. 261-270
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Aim: The influence of exhaustive stretch-shortening cycle exercise (SSC) on skeletal muscle blood flow (BF) during exercise is currently unknown. Methods: Quadriceps femoris (QF) BF was measured in eight healthy men using positron emission tomography before and 3 days after exhaustive SSC exercise. The SSC protocol consisted of maximal and submaximal drop jumps with one leg. Needle biopsies of the vastus lateralis muscles were taken immediately and 2 days after SSC for muscle endothelial nitric oxide synthase (eNOS) and interleukin-1-beta (IL-1beta) mRNA level determinations. Results: All subjects reported subjective muscle soreness after SSC (P < 0.001), which was well in line with a decrease in maximal isometric contraction force (MVC) and increase in serum creatine kinase activity (CK) (P = 0.018). After SSC muscle BF was 25% higher in entire QF (P = 0.043) and in its deep and superficial muscle regions, whereas oxygen uptake remained unchanged (P = 0.893). Muscle biopsies revealed increased IL-1beta (30 min: 152 +/- 75%, P = 0.012 and 2 days: 108 +/- 203%, P = 0.036) but decreased or unchanged eNOS (30 min; -21 +/- 57%, P = 0.050 and 2 days: +101 +/- 204%, P = 0.779) mRNA levels after SSC. Conclusion: It was concluded that fatiguing SSC exercise induces increased muscle BF during exercise, which is likely to be associated with pro-inflammatory processes in the exercised muscle.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Laaksonen, Marko, et al.
(författare)
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Regional differences in blood flow, glucose uptake and fatty acid uptake within quadriceps femoris muscle during dynamic knee-extension exercise
- 2013
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 113:7, s. 1775-1782
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to investigate the regional differences in glucose and fatty acid uptake within skeletal muscle during exercise. Blood flow (BF), glucose uptake (GU) and free fatty acid uptake (FFAU) were measured in four different regions (vastus lateralis, VL; rectus femoris, RF; vastus intermedius, VI; and vastus medialis, VM) of the quadriceps femoris (QF) muscle during low-intensity, knee-extension exercise using positron emission tomography. BF was higher in VI than in VL, RF and VM (P < 0.05). FFAU was higher in VI (P < 0.001) but also in VM (P < 0.05) compared with VL and RF. In contrast, GU was higher in RF compared with VL (P < 0.05) but was not significantly different to VM or VI (both P = NS). FFAU within these four muscle regions correlated significantly with BF (r = 0.951, P < 0.05), whereas no significant relationship was observed between GU and BF (r = 0.352, P = NS). Therefore, skeletal muscle FFAU, but not GU, appears to be associated with BF during low-intensity exercise. The present results also indicate considerable regional differences in substrate use within working QF muscle. As such, an important methodological outcome from these results is that one sample from a specific part of the QF muscle does not represent the response in the entire QF muscle group.
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| 16. |
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| 17. |
- Laaksonen, Marko, et al.
(författare)
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The association between muscle EMG and perfusion in knee extensor muscles
- 2006
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 26:2, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- The relationships between electromyographic (EMG) activity and force as well as muscle blood flow and work have been well established. However, the association between muscle blood flow and EMG activity remains unsolved. Thus, to test the hypothesis that muscle EMG activity relates to muscle perfusion in different compartments of the quadriceps femoris (QF) muscle, 12 healthy male subjects were studied. During two very submaximal exercise bouts, at different exercise intensities, oxygen labelled radiowater and positron emission tomography were used to measure muscle perfusion. In addition, produced force of knee extensors and muscle EMG activity in the vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) muscles were recorded during both exercise bouts. Although the exercise intensity and average force production was higher during the second exercise bout (3815 vs. 5117 N; p=0.007), the mean EMG activity was lower (RF; p<0.001) or unchanged (VL; p=0.722 and VM; p=0.640). During the second exercise period, perfusion also remained unchanged in the entire QF muscle (p=0.223) and in its separate muscles (VL, p=0.703; VM, p=0.141; RF, p=0.113) in a group level. However, the individual changes in muscle perfusion were tightly related to changes in muscle EMG activity in VL (r=0.84; p=0.002) and in VM (r=0.68; p=0.015) but poorly in the RF muscle (r=0.40; p=0.257). In conclusion, the different associations between muscle perfusion and EMG activity in different QF muscles suggests specific functional role of the vasti muscles and the RF muscle.
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| 18. |
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| 19. |
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| 20. |
- Orava, J., et al.
(författare)
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Blunted Metabolic Responses to Cold and Insulin Stimulation in Brown Adipose Tissue of Obese Humans
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 21:11, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. Design and Methods: Using positron emission tomography (PET), cold-and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans were quantified. Further, cold-induced glucose uptake was measured in obese subjects before and after a 5-month conventional weight loss. Results: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. Conclusions: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.
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| 21. |
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| 22. |
- Wu, J., et al.
(författare)
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Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
- 2012
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 150:2, s. 366-376
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Tidskriftsartikel (refereegranskat)abstract
- Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of "beige" cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but, like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we provide evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes. These data provide a foundation for studying this mammalian cell type with therapeutic potential.
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| 23. |
- Bucci, Marco, et al.
(författare)
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Resistance training improves skeletal muscle insulin sensitivity in elderly offspring of overweight and obese mothers.
- 2016
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:1, s. 77-86
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Maternal obesity predisposes offspring to adulthood morbidities, including type 2 diabetes. Type 2 diabetes and insulin resistance have been associated with shortened telomere length. First, we aimed to investigate whether or not maternal obesity influences insulin sensitivity and its relationship with leucocyte telomere length (LTL) in elderly women. Second, we tested whether or not resistance exercise training improves insulin sensitivity in elderly frail women.METHODS: Forty-six elderly women, of whom 20 were frail offspring of lean/normal weight mothers (OLM, BMI ≤26.3 kg/m(2)) and 17 were frail offspring of overweight/obese mothers (OOM, BMI ≥28.1 kg/m(2)), were studied before and after a 4 month resistance training (RT) intervention. Muscle insulin sensitivity of glucose uptake was measured using (18)F-fluoro-2-deoxyglucose and positron emission tomography with computed tomography during a hyperinsulinaemic-euglycaemic clamp. Muscle mass and lipid content were measured using magnetic resonance and LTL was measured using real-time PCR.RESULTS: The OOM group had lower thigh muscle insulin sensitivity compared with the OLM group (p = 0.048) but similar whole body insulin sensitivity. RT improved whole body and skeletal muscle insulin sensitivity in the OOM group only (p = 0.004 and p = 0.013, respectively), and increased muscle mass in both groups (p < 0.01). In addition, in the OOM group, LTL correlated with different thigh muscle groups insulin sensitivity (ρ ≥ 0.53; p ≤ 0.05). Individuals with shorter LTL showed a higher increase in skeletal muscle insulin sensitivity after training (ρ ≥ -0.61; p ≤ 0.05).CONCLUSIONS/INTERPRETATION: Maternal obesity and having telomere shortening were associated with insulin resistance in adult offspring. A resistance exercise training programme may reverse this disadvantage among offspring of obese mothers.TRIAL REGISTRATION: ClinicalTrials.gov NCT01931540.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Hallsten, K, et al.
(författare)
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Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:12, s. 3479-3485
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Tidskriftsartikel (refereegranskat)abstract
- Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone (P < 0.05) and metformin (P < 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% (P < 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% (P < 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1) improves insulin responsiveness in resting skeletal muscle and 2) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise.
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| 28. |
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| 29. |
- Honka, Miikka-Juhani, et al.
(författare)
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Resistance training enhances insulin suppression of endogenous glucose production in elderly women
- 2016
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 120:6, s. 633-639
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Tidskriftsartikel (refereegranskat)abstract
- An altered prenatal environment during maternal obesity predisposes offspring to insulin resistance, obesity, and their consequent comorbidities, type 2 diabetes and cardiovascular disease. Telomere shortening and frailty are additional risk factors for these conditions. The aim of this study was to evaluate the effects of resistance training on hepatic metabolism and ectopic fat accumulation. Thirty-five frail elderly women, whose mothers' body mass index (BMI) was known, participated in a 4-mo resistance training program. Endogenous glucose production (EGP) and hepatic and visceral fat glucose uptake were measured during euglycemic hyperinsulinemia with [F-18] fluorodeoxyglucose and positron emission tomography. Ectopic fat was measured using magnetic resonance spectroscopy and imaging. We found that the training intervention reduced EGP during insulin stimulation [ from 5.4 (interquartile range 3.0, 7.0) to 3.9 (-0.4, 6.1) mu mol.kg body wt(-1).min(-1), P = 0.042] in the whole study group. Importantly, the reduction was higher among those whose EGP was more insulin resistant at baseline (higher than the median) [-5.6 (7.1) vs. 0.1 (5.4) mu mol.kg body wt(-1).min(-1), P = 0.015]. Furthermore, the decrease in EGP was associated with telomere elongation (r = -0.620, P = 0.001). The resistance training intervention did not change either hepatic or visceral fat glucose uptake or the amounts of ectopic fat. Maternal obesity did not influence the studied measures. In conclusion, resistance training improves suppression of EGP in elderly women. The finding of improved insulin sensitivity of EGP with associated telomere lengthening implies that elderly women can reduce their risk for type 2 diabetes and cardiovascular disease with resistance training.
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| 30. |
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| 31. |
- Johansson, BL, et al.
(författare)
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C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients
- 2004
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 286:1, s. E14-E19
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Tidskriftsartikel (refereegranskat)abstract
- Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol·kg-1·min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 μg·kg-1·min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower ( P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion ( P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.
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| 32. |
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| 33. |
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| 34. |
- Karlsson, HKR, et al.
(författare)
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Effects of metformin and rosiglitazone treatment on insulin signaling and glucose uptake in patients with newly diagnosed type 2 diabetes: a randomized controlled study
- 2005
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:5, s. 1459-1467
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Tidskriftsartikel (refereegranskat)abstract
- The effect of metformin or rosiglitazone monotherapy versus placebo on insulin signaling and gene expression in skeletal muscle of patients with newly diagnosed type 2 diabetes was determined. A euglycemic-hyperinsulinemic clamp, combined with skeletal muscle biopsies and glucose uptake measurements over rested and exercised muscle, was performed before and after 26 weeks of metformin (n = 9), rosiglitazone (n = 10), or placebo (n = 11) treatment. Insulin-mediated whole-body and leg muscle glucose uptake was enhanced 36 and 32%, respectively, after rosiglitazone (P < 0.01) but not after metformin or placebo treatment. Insulin increased insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation, IRS-1–associated phosphatidylinositol (PI) 3-kinase activity, and phosphorylation of Akt Ser473 and AS160, a newly described Akt substrate that plays a role in GLUT4 exocytosis, ∼2.3 fold before treatment. These insulin signaling parameters were unaltered after metformin, rosiglitazone, or placebo treatment. Expression of selected genes involved in glucose and fatty acid metabolism in skeletal muscle was unchanged between the treatment groups. Low-intensity acute exercise increased insulin-mediated glucose uptake but was without effect on insulin signaling. In conclusion, the insulin-sensitizing effects of rosiglitazone are independent of enhanced signaling of IRS-1/PI 3-kinase/Akt/AS160 in patients with newly diagnosed type 2 diabetes.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Lahesmaa, M., et al.
(författare)
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Hyperthyroidism increases brown fat metabolism in humans
- 2014
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 99:1
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Tidskriftsartikel (refereegranskat)abstract
- Context: Thyroid hormones are important regulators of brown adipose tissue (BAT) development and function. In rodents, BAT metabolism is up-regulated by thyroid hormones. Objective: The purpose of this article was to investigate the impact of hyperthyroidism on BAT metabolism in humans. Design: This was a follow-up study using positron emission tomography imaging. Main Outcome Measures: Glucose uptake (GU) and perfusion of BAT, white adipose tissue, skeletal muscle, and thyroid gland were measured using [18F]2-fluoro-2-deoxy-D- glucose and [15O]H2Oand positron emission tomography in 10 patients with overt hyperthyroidism and in 8 healthy participants. Five of the hyperthyroid patients were restudied after restoration of euthyroidism. Supraclavicular BAT was quantified with magnetic resonance imaging or computed tomography and energy expenditure (EE) with indirect calorimetry. Results: Compared with healthy participants, hyperthyroid participants had 3-fold higher BAT GU (2.7 ± 2.3 vs 0.9 ± 0.1 ±mol/100 g/min, P = .0013), 90% higher skeletal muscle GU (P < .005), 45% higher EE (P<.005), and a 70% higher lipid oxidation rate (P = .001). These changes were reversible after restoration of euthyroidism. During hyperthyroidism, serum free T4 and free T3 were strongly associated with EE and lipid oxidation rates (P < .001). TSH correlated inversely with BAT and skeletal muscle glucose metabolism (P < .001). Hyperthyroidism had no effect on BAT perfusion, whereas it stimulated skeletal muscle perfusion (P = .04). Thyroid gland GU did not differ between hyperthyroid and euthyroid study subjects. Conclusions: Hyperthyroidism increases GU in BAT independently of BAT perfusion. Hyperthyroid patients are characterized by increased skeletal muscle metabolism and lipid oxidation rates. (J Clin Endocrinol Metab 99: E28-E35, 2014). © Copyright 2014 by The Endocrine Society.
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| 39. |
- Lasar, D., et al.
(författare)
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Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte Inducibility through Glycerol Kinase
- 2018
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 22:3, s. 760-773
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Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPAR alpha, beta/delta, and gamma, respectively. We found that both PPARa and beta/delta are dispensable for brown fat function. In contrast, we could show that ablation of PPAR gamma in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by beta-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization. We identified glycerol kinase (Gyk) as a partial mediator of PPAR gamma function and could show that Gyk expression correlates with brown fat thermogenic capacity in human brown fat biopsies. Thus, Gyk might constitute the link between PPAR gamma-mediated regulation of brown fat function and activation by b-adrenergic signaling.
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| 40. |
- Latva-Rasku, Aino, et al.
(författare)
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The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity : A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients.
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:5, s. 931-937
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS: This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA1c 6.5-10.5% (48-91 mmol/mol) and ≥3 months of stable treatment with metformin, dipeptidyl peptidase 4 inhibitor, or their combination. Patients were randomized 1:1 to receive 10 mg dapagliflozin or placebo daily for 8 weeks. Before and after the intervention, tissue insulin sensitivity was measured using [18F]-fluorodeoxyglucose and positron emission tomography during hyperinsulinemic-euglycemic clamp. Liver proton density fat fraction (PDFF) and adipose tissue volumes were assessed using MRI, and blood biomarkers were analyzed.RESULTS: After 8 weeks, glycemic control was improved by dapagliflozin (placebo-corrected change in HbA1c -0.39%, P < 0.01), but whole-body glucose uptake was not increased (P = 0.90). Tissue-specific insulin-stimulated glucose uptake did not change in skeletal muscle, liver, myocardium, or white and brown adipose tissue, and endogenous glucose production remained unaffected. However, there were significant placebo-corrected decreases in liver PDFF (-3.74%, P < 0.01), liver volume (-0.10 L, P < 0.05), visceral adipose tissue volume (-0.35 L, P < 0.01), interleukin-6 (-1.87 pg/mL, P < 0.05), and N-terminal prohormone of brain natriuretic peptide (-96 ng/L, P = 0.03).CONCLUSIONS: In this study, 8 weeks of treatment with dapagliflozin reduced liver PDFF and the volume of visceral adipose tissue in obese patients with type 2 diabetes. Although glycemic control was improved, no effect on tissue-level insulin sensitivity was observed.
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| 41. |
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| 42. |
- Lidell, Martin, 1970, et al.
(författare)
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Evidence for two types of brown adipose tissue in humans
- 2013
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 19:5, s. 631-634
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Tidskriftsartikel (refereegranskat)abstract
- The previously observed supraclavicular depot of brown adipose tissue (BAT) in adult humans was
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| 43. |
- Motiani, P., et al.
(författare)
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Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity
- 2019
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Ingår i: Obesity science & practice. - : WILEY. - 2055-2238. ; 5:3, s. 258-272
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Tidskriftsartikel (refereegranskat)abstract
- Introduction New strategies for weight loss and weight maintenance in humans are needed. Human brown adipose tissue (BAT) can stimulate energy expenditure and may be a potential therapeutic target for obesity and type 2 diabetes. However, whether exercise training is an efficient stimulus to activate and recruit BAT remains to be explored. This study aimed to evaluate whether regular exercise training affects cold-stimulated BAT metabolism and, if so, whether this was associated with changes in plasma metabolites. Methods Healthy sedentary men (n = 11; aged 31 [SD 7] years; body mass index 23 [0.9] kg m(-2); VO2 max 39 [7.6] mL min(-1) kg(-1)) participated in a 6-week exercise training intervention. Fasting BAT and neck muscle glucose uptake (GU) were measured using quantitative [F-18]fluorodeoxyglucose positron emission tomography-magnetic resonance imaging three times: (1) before training at room temperature and (2) before and (3) after the training period during cold stimulation. Cervico-thoracic BAT mass was measured using MRI signal fat fraction maps. Plasma metabolites were analysed using nuclear magnetic resonance spectroscopy. Results Cold exposure increased supraclavicular BAT GU by threefold (p < 0.001), energy expenditure by 59% (p < 0.001) and plasma fatty acids (p < 0.01). Exercise training had no effect on cold-induced GU in BAT or neck muscles. Training increased aerobic capacity (p = 0.01) and decreased visceral fat (p = 0.02) and cervico-thoracic BAT mass (p = 0.003). Additionally, training decreased very low-density lipoprotein particle size (p = 0.04), triglycerides within chylomicrons (p = 0.04) and small high-density lipoprotein (p = 0.04). Conclusions Although exercise training plays an important role for metabolic health, its beneficial effects on whole body metabolism through physiological adaptations seem to be independent of BAT activation in young, sedentary men.
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| 44. |
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| 45. |
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| 46. |
- Perdikari, A., et al.
(författare)
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BATLAS: Deconvoluting Brown Adipose Tissue
- 2018
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- Recruitment and activation of thermogenic adipocytes have received increasing attention as a strategy to improve systemic metabolic control. The analysis of brown and brite adipocytes is complicated by the complexity of adipose tissue biopsies. Here, we provide an in-depth analysis of pure brown, brite, and white adipocyte transcriptomes. By combining mouse and human transcriptome data, we identify a gene signature that can classify brown and white adipocytes in mice and men. Using a machine-learning-based cell deconvolution approach, we develop an algorithm proficient in calculating the brown adipocyte content in complex human and mouse biopsies. Applying this algorithm, we can show in a human weight loss study that brown adipose tissue (BAT) content is associated with energy expenditure and the propensity to lose weight. This online available tool can be used for in-depth characterization of complex adipose tissue samples and may support the development of therapeutic strategies to increase energy expenditure in humans.
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| 47. |
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| 48. |
- Tervaniemi, MH, et al.
(författare)
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NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 22745-
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Tidskriftsartikel (refereegranskat)abstract
- Psoriatic skin differs distinctly from normal skin by its thickened epidermis. Most gene expression comparisons utilize full-thickness biopsies, with substantial amount of dermis. We assayed the transcriptomes of normal, lesional and non-lesional psoriatic epidermis, sampled as split-thickness skin grafts, with 5′-end RNA sequencing. We found that psoriatic epidermis contains more mRNA per total RNA than controls and took this into account in the bioinformatic analysis. The approach highlighted innate immunity-related pathways in psoriasis, including NOD-like receptor (NLR) signaling and inflammasome activation. We demonstrated that the NLR signaling genes NOD2, PYCARD, CARD6 and IFI16 are upregulated in psoriatic epidermis and strengthened these findings by protein expression. Interestingly, PYCARD, the key component of the inflammasome, showed an altered expression pattern in the lesional epidermis. The profiling of non-lesional skin highlighted PSORS4 and mitochondrially encoded transcripts, suggesting that their gene expression is altered already before the development of lesions. Our data suggest that all components needed for the active inflammasome are present in the keratinocytes of psoriatic skin. The characterization of inflammasome pathways provides further opportunities for therapy. Complementing previous transcriptome studies, our approach gives deeper insight into the gene regulation in psoriatic epidermis.
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| 49. |
- U-Din, Mueez, et al.
(författare)
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Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD + metabolism in humans
- 2023
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Ingår i: Cell Reports. - 2211-1247. ; 42:9
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Tidskriftsartikel (refereegranskat)abstract
- Cold-induced brown adipose tissue (BAT) activation is considered to improve metabolic health. In murine BAT, cold increases the fundamental molecule for mitochondrial function, nicotinamide adenine dinucleotide (NAD+), but limited knowledge of NAD+ metabolism during cold in human BAT metabolism exists. We show that cold increases the serum metabolites of the NAD+ salvage pathway (nicotinamide and 1-methylnicotinamide) in humans. Additionally, individuals with cold-stimulated BAT activation have decreased levels of metabolites from the de novo NAD+ biosynthesis pathway (tryptophan, kynurenine). Serum nicotinamide correlates positively with cold-stimulated BAT activation, whereas tryptophan and kynurenine correlate negatively. Furthermore, the expression of genes involved in NAD+ biosynthesis in BAT is related to markers of metabolic health. Our data indicate that cold increases serum tryptophan conversion to nicotinamide to be further utilized by BAT. We conclude that NAD+ metabolism is activated upon cold in humans and is probably regulated in a coordinated fashion by several tissues.
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