| 1. |
- Baeckdahl, Jesper, et al.
(författare)
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Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin
- 2021
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:9, s. 1869-
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of cellular heterogeneity and architecture to white adipose tissue (WAT) function is poorly understood. Herein, we combined spatially resolved transcriptional profiling with single-cell RNA sequencing and image analyses to map human WAT composition and structure. This identified 18 cell classes with unique propensities to form spatially organized homo-and heterotypic clusters. Of these, three constituted mature adipocytes that were similar in size, but distinct in their spatial arrangements and transcriptional profiles. Based on marker genes, we termed these Adipo(LEP), Adipo(PLIN), and Adipo(SAA). We confirmed, in independent datasets, that their respective gene profiles associated differently with both adipocyte and whole-body insulin sensitivity. Corroborating our observations, insulin stimulation in vivo by hyperinsulinemic-euglycemic clamp showed that only Adipo(PLIN) displayed a transcriptional response to insulin. Altogether, by mining this multimodal resource we identify that human WAT is composed of three classes of mature adipocytes, only one of which is insulin responsive.
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| 2. |
- Fabian, Botond, et al.
(författare)
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Diagnostic challenges in patients with reninomas and extrarenal renin-producing tumours
- 2024
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Ingår i: Clinical Endocrinology. - 0300-0664 .- 1365-2265. ; 101:1, s. 3-9
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Forskningsöversikt (refereegranskat)abstract
- Renin-secreting tumours are rare causes of secondary hypertension and hypokalaemia. They are usually surgically curable, hence proper diagnostic work-up and tumour localisation is essential. In this paper, we present three Swedish patients recently diagnosed with renin secreting tumours, two with reninomas and one with an extrarenal renin-producing tumour, to illustrate diagnostic challenges. We also discuss the biochemical work-up, the pros and cons of different imaging techniques (computer tomography [CT], magnetic resonance imaging and [18F]fluorodeoxyglucose-positron emission tomography-CT), as well as how renal vein sampling (RVC) may contribute to localisation of the tumour.
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| 3. |
- Massier, Lucas, et al.
(författare)
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An integrated single cell and spatial transcriptomic map of human white adipose tissue
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell studies of human white adipose tissue (WAT) provide insights into the specialized cell types in the tissue. Here the authors combine publicly available and newly generated high-resolution and bulk transcriptomic results from multiple human datasets to provide a comprehensive cellular map of white adipose tissue. To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.
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| 4. |
- Nasr, Patrik, et al.
(författare)
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A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease : the ACCESS-ESLD study protocol
- 2023
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Ingår i: BMC Gastroenterology. - : BioMed Central (BMC). - 1471-230X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients.METHODS: In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations.DISCUSSION: The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes.TRIAL REGISTRATION: Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05502198 .
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| 5. |
- Nylander, Elin, et al.
(författare)
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Five-year outcomes of ADHD diagnosed in adulthood.
- 2021
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Ingår i: Scandinavian journal of psychology. - : Wiley. - 1467-9450 .- 0036-5564. ; 62:1, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- There is a dearth of long-term follow-up studies of adults diagnosed with ADHD. Here, the aim was to evaluate long-term outcomes in a group of ADHD patients diagnosed in adulthood and receiving routine psychiatric health care. Adults diagnosed with any type of ADHD (n=52) and healthy controls (n=73) were assessed at baseline and at a 5-year follow-up, using Global Assessment of Functioning (GAF), Clinical Global Impression (CGI), Brown ADD Scale (BADDS) and Adult ADHD Self-Report Scale (ASRS). A multivariate regression method was used to identify factors predicting 5-year outcomes, including baseline ratings, medication intensity, comorbidity, intelligence quotient (IQ), age, and sex. After 5years, ADHD patients reported fewer and/or less severe symptoms compared to baseline, but remained at clinically significant symptom levels and with functional deficits. Baseline self-reports of ADHD symptoms predicted their own 5-year outcome and low baseline functioning level predicted improved global functioning at follow-up. Factors previously reported to predict short-term outcomes (i.e., medication, comorbidity, IQ, age, and sex) did not anticipate long-term outcomes in present study.
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| 6. |
- Nylander, Elin, et al.
(författare)
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The Quantified Behavioural Test Plus (QbTest plus ) in adult ADHD
- 2023
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Ingår i: Nordic Psychology. - : Informa UK Limited. - 1901-2276 .- 1904-0016. ; 75:1, s. 20-34
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Tidskriftsartikel (refereegranskat)abstract
- The Quantified Behavioural Test Plus (QbTest+) is widely used in clinical practice to assess patients with attention-deficit hyperactivity disorder (ADHD). This study mapped its behaviour in a group of adults with ADHD. Does it signal problems with impulsivity, attention and/or activity? To what extent are patients' self-reported problems reflected in QbTest performance? Does Qb testing foretell the future, as reflected in the patients' and clinicians' judgements 4 years later? We here recorded the three QbTest+ cardinals-QbActivity, QbImpulsivity and QbInattention - in 67 consecutive ADHD patients diagnosed in adulthood. Among the 54 patients who medicated as usual on the day of testing, 35 (65%) scored above the clinical cut-off (Q-score >= 1.25) on at least one of the QbTest+ cardinals. Out of the 13 patients who suspended medication prior to the test, 11 (85%) scored above the clinical cut-off on at least one of the Qb-variables. There were modest associations between QbTest+ cardinals and symptom self-ratings [Brown ADD scale (BADDS); Adult Self-Report Scale (ASRS)]. Forty-one patients completed a second QbTest+ approximately 4 years after the first. Performance was improved on the follow-up test and fewer patients scored in the clinical range (34%). The scores on the QbInattention cardinal at baseline correlated positively with BADDS and ASRS self-ratings at the 4-year follow-up.
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| 7. |
- Rydén, Henric, et al.
(författare)
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Chemical shift encoding using asymmetric readout waveforms.
- 2021
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 85:3, s. 1468-1480
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To describe a new method for encoding chemical shift using asymmetric readout waveforms that enables more SNR-efficient fat/water imaging.METHODS: Chemical shift was encoded using asymmetric readout waveforms, rather than conventional shifted trapezoid readouts. Two asymmetric waveforms are described: a triangle and a spline. The concept was applied to a fat/water separated RARE sequence to increase sampling efficiency. The benefits were investigated through comparisons to shifted trapezoid readouts. Using asymmetric readout waveforms, the scan time was either shortened or maintained to increase SNR. A matched in-phase waveform is also described that aims to improve the SNR transfer function of the fat and water estimates. The sequence was demonstrated for cervical spine, musculoskeletal (MSK), and optic nerve applications at 3T and compared with conventional shifted readouts.RESULTS: blurring. Maintaining the scan times and using asymmetric readout waveforms achieved an SNR improvement in agreement with the prolonged sampling duration.CONCLUSIONS: Asymmetric readout waveforms offer an additional degree of freedom in pulse sequence designs where chemical shift encoding is desired. This can be used to significantly shorten scan times or to increase SNR with maintained scan time.
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| 8. |
- Rydén, Mikael, et al.
(författare)
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Lipolysis defect in people with obesity who undergo metabolic surgery
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Inc.. - 0954-6820 .- 1365-2796. ; 292:4, s. 667-678
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cross-sectional studies demonstrate that catecholamine stimulation of fat cell lipolysis is blunted in obesity. We investigated whether this defect persists after substantial weight loss has been induced by metabolic surgery, and whether it is related to the outcome.DESIGN/METHODS: Patients with obesity not able to successfully reduce body weight by conventional means (n = 126) were investigated before and 5 years after Roux-en-Y gastric bypass surgery (RYGB). They were compared with propensity-score matched subjects selected from a control group (n = 1017), and with the entire group after adjustment for age, sex, body mass index (BMI), fat cell volume and other clinical parameters. Catecholamine-stimulated lipolysis (glycerol release) was investigated in isolated fat cells using noradrenaline (natural hormone) or isoprenaline (synthetic beta-adrenoceptor agonist).RESULTS: Following RYGB, BMI was reduced from 39.9 (37.5-43.5) (median and interquartile range) to 29.5 (26.7-31.9) kg/m2 (p < 0.0001). The post-RYGB patients had about 50% lower lipolysis rates compared with the matched and total series of controls (p < 0.0005). Nordrenaline activation of lipolysis at baseline was associated with the RYGB effect; those with high lipolysis activation (upper tertile) lost 30%-45% more in body weight, BMI or fat mass than those with low (bottom tertile) initial lipolysis activation (p < 0.0007).CONCLUSION: Patients with obesity requiring metabolic surgery have impaired ability of catecholamines to stimulate lipolysis, which remains despite long-term normalization of body weight by RYGB. Furthermore, preoperative variations in the ability of catecholamines to activate lipolysis may predict the long-term reduction in body weight and fat mass.
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| 9. |
- Sarsenbayeva, Assel
(författare)
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Adverse drug effects on glucose and lipid metabolism: is human adipose tissue of importance?
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many pharmacological agents that are widely prescribed in clinical practice have adverse metabolic effects, such as hyperglycaemia, insulin resistance, and diabetes. Among such drugs are antipsychotics, prescribed for treatment of schizophrenia; statins, which inhibit cholesterol synthesis and prevent cardiovascular events; finally, potent anti-inflammatory agents, glucocorticoids. This thesis is focused on investigating the direct effects of second-generation antipsychotics (SGAs), statins, and glucocorticoids on human adipose tissue metabolism and inflammation, particularly in the light of macrophage-adipocyte cross talk.In Paper I, the direct effects of SGAs on adipose tissue glucose and lipid metabolism were studied. SGAs had a mild effect on adipocyte glucose uptake and lipolysis at therapeutic concentrations. At supra-therapeutic concentrations, the drugs demonstrated anti-inflammatory potential, reducing the expression of pro-inflammatory genes in the adipose tissue.In Paper II, the anti-inflammatory potential of SGAs and dexamethasone was further explored. The effects of the drugs on macrophage phenotype and communication with adipocytes were addressed. SGAs at supra-therapeutic concentrations exerted mild anti-inflammatory effects on macrophages, while dexamethasone acted as a potent anti-inflammatory agent and promoted alternatively activated M2 macrophage phenotype. Macrophages, in turn, induced marked upregulation of pro-inflammatory genes in adipocytes, which was partially reversed by dexamethasone, while SGAs had no effects on macrophage-adipocyte communication.In Paper III, we examined the association of statin therapy on systemic insulin resistance and direct effects statins on human adipose tissue and pancreatic islets functions. We also studied association of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the enzyme involved in cholesterol synthesis, and genetic inhibition of HMGCR seen with certain polymorphisms with adipose tissue and plasma metabolome. Our study demonstrated minor direct effects of statins on human adipose tissue metabolism and insulin secretion in pancreatic islets. We observed that HMGCR expression was associated with a number of metabolic and mitochondrial pathways in the adipose tissue, while LDL-lowering HMGCR polymorphism was negatively associated with plasma phosphatidylcholines and sphingomyelins. In Paper IV we studied the effects of glucocorticoids on adipose tissue fibrosis, particularly in terms of macrophage-preadipocyte communication. Together with inflammation, adipose tissue fibrosis impairs adipocyte metabolism and functions. We observed that glucocorticoids at high concentrations have pro-fibrotic effects in adipose tissue. Macrophage-preadipocyte co-culture data showed that macrophages stimulate phenotypic switch of preadipocytes to pro-fibrotic myofibroblasts, and this effect was exacerbated by dexamethasone. Our findings suggest that pro-fibrotic effects of excess glucocorticoids on adipose tissue are at least partially mediated via their effects on macrophage-preadipocyte communication.We conclude that SGAs and statins have a mild direct effect on adipose tissue metabolism and their diabetogenic effects could to be induced via other organs, such as brain, liver or muscle. By contrast, glucocorticoids, directly impair adipose tissue metabolism and exacerbates adipose tissue fibrosis, which could be one of the contributing factors to their metabolic adverse effects.
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