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Article ; Online: [No title information]

Rydén, Mikael

2023 Volume 120

Title translation	Paradigmskifte i behandlingen av fetma och typ 2-diabetes.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2 ; Obesity
Language	Swedish
Publishing date	2023-03-21
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	391010-6
ISSN	1652-7518 ; 0023-7205
ISSN (online)	1652-7518
ISSN	0023-7205
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Article: Insights from Studies of White Adipose Tissue Using Single-Cell Approaches.

Mejhert, Niklas / Rydén, Mikael

Handbook of experimental pharmacology

2022 Volume 274, Page(s) 131–144

Abstract: Technologies allowing studies at single-cell resolution have provided important insights into how different cell populations contribute to tissue function. Application of these methods to white adipose tissue (WAT) has revealed how various metabolic ... ...

Abstract	Technologies allowing studies at single-cell resolution have provided important insights into how different cell populations contribute to tissue function. Application of these methods to white adipose tissue (WAT) has revealed how various metabolic aspects of this organ, such as insulin response, inflammation and tissue expansion, are regulated by specific WAT resident cells, including different subtypes of adipocytes, adipocyte progenitors as well as immune and endothelial cells. In this chapter, we provide an overview of the different technical approaches, their strengths and weaknesses, and summarize how these studies have improved our understanding of WAT function in health and disease.
MeSH term(s)	Adipocytes, White/metabolism ; Adipose Tissue/metabolism ; Adipose Tissue, White/metabolism ; Endothelial Cells/metabolism ; Humans ; Insulin Resistance ; Obesity/metabolism
Language	English
Publishing date	2022-03-22
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0171-2004
ISSN	0171-2004
DOI	10.1007/164_2021_578
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Article ; Online: Understanding the complexity of insulin resistance.

Mejhert, Niklas / Rydén, Mikael

Nature reviews. Endocrinology

2022 Volume 18, Issue 5, Page(s) 269–270

MeSH term(s)	Humans ; Insulin ; Insulin Resistance
Chemical Substances	Insulin
Language	English
Publishing date	2022-02-09
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2489381-X
ISSN	1759-5037 ; 1759-5029
ISSN (online)	1759-5037
ISSN	1759-5029
DOI	10.1038/s41574-022-00648-9
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Zs.A 6336: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 93: Show issues

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Article ; Online: Human white adipose tissue: A highly dynamic metabolic organ.

Arner, Peter / Rydén, Mikael

Journal of internal medicine

2022 Volume 291, Issue 5, Page(s) 611–621

Abstract: Recent technological developments have allowed determination of the age of fat cells and their lipids in adult humans. In contrast to prior views, this has demonstrated a high turnover rate of the fat cells (10%/year) and their unilocular lipid droplets ( ...

Abstract	Recent technological developments have allowed determination of the age of fat cells and their lipids in adult humans. In contrast to prior views, this has demonstrated a high turnover rate of the fat cells (10%/year) and their unilocular lipid droplets (six times/10 years). Fat cell turnover is increased in obesity and when adipose tissue is composed of many but small adipocytes (hyperplasia, a benign adipose phenotype). While fat mass gain increases adipocyte number and size, only the latter is altered (decreased) after weight loss, which may facilitate weight regain. Fat cell lipid turnover is attenuated in subjects with excess body fat. In the subcutaneous region, this dysregulation occurs already in the overweight state while in the visceral depot, it is only observed in severe obesity. This may explain why the latter depot is particularly pernicious in the overweight/obese state as it allows for more rapid lipid fluxes between visceral fat and the liver. Adipose lipid turnover decreases during ageing due to impaired breakdown (lipolysis) of stored triglycerides. If this decline is not compensated by reduced adipocyte lipid uptake, bodyweight will increase over time. In concordance with this, low lipolysis rates are a risk factor for future weight gain and glucose intolerance. Adipose lipid turnover is also decreased in insulin resistance and certain forms of dyslipidemia. Altogether, adult human adipose tissue is in a highly dynamic state. Alterations in the turnover of fat cells and their lipids are therefore novel factors to consider in the pathophysiology of common metabolic disorders.
MeSH term(s)	Adipocytes/metabolism ; Adipose Tissue/metabolism ; Humans ; Insulin Resistance ; Metabolic Diseases/metabolism ; Obesity/metabolism ; Overweight/metabolism ; Triglycerides/metabolism
Chemical Substances	Triglycerides
Language	English
Publishing date	2022-01-16
Publishing country	England
Document type	Journal Article
ZDB-ID	96274-0
ISSN	1365-2796 ; 0954-6820
ISSN (online)	1365-2796
ISSN	0954-6820
DOI	10.1111/joim.13435
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Article: On the origin of human adipocytes and the contribution of bone marrow-derived cells.

Rydén, Mikael

Adipocyte

2016 Volume 5, Issue 3, Page(s) 312–317

Abstract: In the last decade, results in both animal models and humans have demonstrated that white adipocytes are generated over the entire life-span. This adds to the plasticity of adipose tissue and alterations in adipocyte turnover are linked to metabolic ... ...

Abstract	In the last decade, results in both animal models and humans have demonstrated that white adipocytes are generated over the entire life-span. This adds to the plasticity of adipose tissue and alterations in adipocyte turnover are linked to metabolic dysfunction. Adipocytes are derived from precursors present primarily in the perivascular areas of adipose tissue but their precise origin remains unclear. The multipotent differentiation capacity of bone marrow-derived cells (BMDC) has prompted the suggestion that BMDC may contribute to different cell tissue pools, including adipocytes. However, data in murine transplantation models have been conflicting and it has been a matter of debate whether BMDC actually differentiate into adipocytes or just fuse with resident fat cells. To resolve this controversy in humans, we recently performed a study in 65 subjects that had undergone bone marrow transplantation. Using a set of newly developed assays including single cell genome-wide analyses of mature adipocytes, we demonstrated that bone marrow contributes with approximately 10 % to the adipocyte pool. This proportion was more than doubled in obesity, suggesting that BMDC may constitute a reserve pool for adipogenesis, particularly upon weight gain. This commentary discusses the possible relevance of these and other recent findings for human pathophysiology.
Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Comment ; Journal Article
ISSN	2162-3945
ISSN	2162-3945
DOI	10.1080/21623945.2015.1134403
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Article ; Online: Diagnostic challenges in patients with reninomas and extrarenal renin-producing tumours.

Fabian, Botond / Ragnarsson, Oskar / Prazic, Aleksandar / Rydén, Mikael / Volpe, Cristina / Lindgren, Ola

Clinical endocrinology

2024

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 ... ...

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.
Language	English
Publishing date	2024-05-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	121745-8
ISSN	1365-2265 ; 0300-0664
ISSN (online)	1365-2265
ISSN	0300-0664
DOI	10.1111/cen.15069
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Article ; Online: Insulin resistance in adipocytes: Novel insights into the pathophysiology of metabolic syndrome.

Kerr, Alastair G / Andersson, Daniel P / Rydén, Mikael / Arner, Peter

Clinical nutrition (Edinburgh, Scotland)

2023 Volume 43, Issue 2, Page(s) 468–475

Abstract: Background: Insulin resistance in all major target tissues is present in metabolic syndrome (MetS). The resistance in adipocytes is not well described and was presently examined.: Methods: In this observational study on isolated abdominal white ... ...

Abstract	Background: Insulin resistance in all major target tissues is present in metabolic syndrome (MetS). The resistance in adipocytes is not well described and was presently examined. Methods: In this observational study on isolated abdominal white subcutaneous adipocytes from 419 adults, concentration-response effects of insulin on lipolysis inhibition (glycerol release) and lipogenesis stimulation (glucose conversion to total lipids) were determined. Insights into early and late insulin signaling events were obtained through the determination of insulin sensitivity (half maximum effective concentration) and responsiveness (maximum effect), respectively. In a subgroup of 132 subjects, we analyzed the subcutaneous adipose mRNA expression of genes in the canonical insulin signaling pathway using microarray. These results were validated using quantitative real-time polymerase chain reaction in 74 individuals. Results: While the insulin responsiveness was similar in subjects with or without Mets, the sensitivity to insulin-mediated inhibition of lipolysis and stimulation of lipogenesis was ∼tenfold lower in subjects with MetS (p < 0.0001). When age, sex, adipocyte volume, body mass index and body shape were considered, only the antilipolytic resistance was independently associated with MetS. The mRNA expression of several genes in the canonical insulin signaling pathway were altered in MetS (p < 0.0006 or better) where the mRNA levels of insulin receptor substrate 2 associated with the antilipolytic effect (Rho = 0.34; p = 0.0016). Conclusion: The sensitivities of the antilipolytic and lipogenic effects of insulin are decreased in the MetS but only antilipolysis remains significant after multiple regression analysis. This resistance is localized at initial and receptor-near events in hormone signaling involving insulin receptor substrate 2.
MeSH term(s)	Adult ; Humans ; Insulin Resistance ; Insulin Receptor Substrate Proteins/metabolism ; Metabolic Syndrome/metabolism ; Adipocytes/metabolism ; Insulin/metabolism ; RNA, Messenger/metabolism
Chemical Substances	Insulin Receptor Substrate Proteins ; Insulin ; RNA, Messenger
Language	English
Publishing date	2023-12-19
Publishing country	England
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2023.12.012
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Article ; Online: Novel aspects on the role of white adipose tissue in type 2 diabetes.

Mejhert, Niklas / Rydén, Mikael

Current opinion in pharmacology

2020 Volume 55, Page(s) 47–52

Abstract: White adipose tissue (WAT) is a highly dynamic organ that can vary considerably in mass depending on energy balance. Data from recent cross-sectional and prospective clinical studies have revealed a set of mechanisms that link WAT dysfunction to type 2 ... ...

Abstract	White adipose tissue (WAT) is a highly dynamic organ that can vary considerably in mass depending on energy balance. Data from recent cross-sectional and prospective clinical studies have revealed a set of mechanisms that link WAT dysfunction to type 2 diabetes. This review focuses on three of the most important pathophysiological processes that distinguish WAT in the insulin resistant state: regional WAT distribution, adipocyte hypertrophy and lipid turnover. Together, these disturbances attenuate the lipid storage capacity of WAT leading to ectopic fat deposition in peripheral tissues such as skeletal muscle, liver and vessels ultimately leading to type 2 diabetes and cardiovascular complications. The possible approaches to therapeutically target dysfunctional WAT are also discussed.
MeSH term(s)	Adipocytes/metabolism ; Adipose Tissue, White/metabolism ; Animals ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Humans ; Lipid Metabolism ; Phenotype
Language	English
Publishing date	2020-10-26
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2020.09.008
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Article ; Online: Adipose Insulin Resistance Associates With Dyslipidemia Independent of Liver Resistance and Involves Early Hormone Signaling.

Kerr, Alastair G / Andersson, Daniel P / Dahlman, Ingrid / Rydén, Mikael / Arner, Peter

Arteriosclerosis, thrombosis, and vascular biology

2023 Volume 43, Issue 6, Page(s) 1054–1065

Abstract: Background: Adipose tissue insulin resistance is linked to altered plasma levels of triglycerides and HDL (high-density lipoprotein)-cholesterol. However, its degree of independence from liver resistance and different metabolic traits (lipolysis, ... ...

Abstract	Background: Adipose tissue insulin resistance is linked to altered plasma levels of triglycerides and HDL (high-density lipoprotein)-cholesterol. However, its degree of independence from liver resistance and different metabolic traits (lipolysis, lipogenesis) effected is not clear and was presently investigated. Methods: In 3290 adult subjects, plasma levels of triglycerides and HDL-cholesterol were cross-sectionally measured and related to interindividual variations in measures of insulin resistance in the liver (homeostasis mode assessment of insulin resistance index) or adipose tissue (Adipo-IR index). In subgroups, insulin-induced antilipolysis and lipogenesis in isolated subcutaneous fat cells (n=578) were determined alongside global adipose tissue gene expression (n=132). Results: Using linear regression, homeostasis mode assessment of insulin resistance and Adipo-IR strongly correlated with the plasma lipids explaining 33% of the variations in triglycerides. Together with other variables (age, sex, body mass index, cardiometabolic disorders, nicotine use, ethnicity, and physical activity) in multiple regression, homeostasis mode assessment of insulin resistance, and Adipo-IR each remained an important regressor for triglycerides and HDL-cholesterol ( Conclusions: Markers of insulin resistance in the liver and adipose tissue each associate strongly, and independently of each other, to elevated triglycerides and decreased HDL levels. At the fat cell, early insulin receptor signaling and sensitivity, but not maximum insulin action contributes to the variations in circulating triglycerides and HDL-cholesterol.
MeSH term(s)	Adult ; Humans ; Insulin Resistance ; Receptor, Insulin ; Obesity/metabolism ; Adipose Tissue/metabolism ; Triglycerides ; Insulin ; Cholesterol, HDL ; Liver/metabolism ; Dyslipidemias/diagnosis ; Dyslipidemias/genetics
Chemical Substances	Receptor, Insulin (EC 2.7.10.1) ; Triglycerides ; Insulin ; Cholesterol, HDL
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.123.319227
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Article ; Online: Sex differences in adipose insulin resistance are linked to obesity, lipolysis and insulin receptor substrate 1.

Arner, Peter / Viguerie, Nathalie / Massier, Lucas / Rydén, Mikael / Astrup, Arne / Blaak, Ellen / Langin, Dominique / Andersson, Daniel Peter

International journal of obesity (2005)

2024

Abstract: Background/objective: Insulin resistance is more prominent in men than women. If this involves adipose tissue is unknown and was presently examined.: Subjects/methods: AdipoIR (in vivo adipose insulin resistance index) was measured in 2344 women and ... ...

Abstract	Background/objective: Insulin resistance is more prominent in men than women. If this involves adipose tissue is unknown and was presently examined. Subjects/methods: AdipoIR (in vivo adipose insulin resistance index) was measured in 2344 women and 787 men. In 259 of the women and 54 of the men, insulin induced inhibition of lipolysis (acylglycerol breakdown) and stimulation of lipogenesis (glucose conversion to acylglycerols) were determined in subcutaneous adipocytes; in addition, basal (spontaneous) lipolysis was also determined in the fat cells. In 234 women and 115 men, RNAseq expression of canonical insulin signal genes were measured in subcutaneous adipose tissue. Messenger RNA transcripts of the most discriminant genes were quantified in 175 women and 109 men. Results: Men had higher AdipoIR values than women but only when obesity (body mass index 30 kg/m Conclusions: In obesity, adipose tissue insulin resistance is more pronounced in men than in women. The mechanism involves less efficient insulin-mediated inhibition of adipocyte lipolysis, increased basal rate of lipolysis and decreased adipose expression of a key element of insulin signaling, IRS1.
Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	752409-2
ISSN	1476-5497 ; 0307-0565
ISSN (online)	1476-5497
ISSN	0307-0565
DOI	10.1038/s41366-024-01501-x
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