Genome-Wide Association Study of Diabetogenic Adipose Morphology in the GENetics of Adipocyte Lipolysis (GENiAL) Cohort

Lundbäck, Veroniqa; Kulyté, Agné; Arner, Peter; Strawbridge, Rona J.; Dahlman, Ingrid

doi:10.3390/cells9051085

Cited by 10 publications

(15 citation statements)

References 37 publications

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“…GENiAL study participants. The GENetics of Adipocyte Lipolysis (GENiAL) cohort included 273 men and 718 women and have been described previously 70 . Briefly, subjects in the GENiAL cohort were recruited by local advertisement to examine the regulation of fat cell function.…”

Section: Methodsmentioning

confidence: 99%

“…None were treated with insulin, glitazones, or glucagon-like-peptide analogs. Data on clinical variables are summarized elsewhere 70 . The study was approved by the local ethics committee at the Huddinge University Hospital (D. no.…”

Section: Methodsmentioning

confidence: 99%

“…Informed consent was obtained from all participants. Included in this study were 948 subjects from the GENiAL cohort with adipose morphology data available 70 .…”

Section: Methodsmentioning

confidence: 99%

“…Genetic analysis of the GENiAL cohort. The genetic analysis of the GENiAL cohort has been described previously 70 . After quality control, 894 samples were available for analysis.…”

Section: Methodsmentioning

confidence: 99%

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LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes

et al. 2021

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Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-β) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Informed consent was obtained from all participants. Included in this study were 948 subjects from the GENiAL cohort with adipose morphology data available 70 .…”

Section: Methodsmentioning

confidence: 99%

“…Genetic analysis of the GENiAL cohort. The genetic analysis of the GENiAL cohort has been described previously 70 . After quality control, 894 samples were available for analysis.…”

Section: Methodsmentioning

confidence: 99%

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LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes

et al. 2021

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“…Transmembrane protein 200A (TMEM200A) (Ensembl ID: ENSG00000164484) is also a member of the TMEM gene family, located on chromosome 6q23.1, with a total length of 77.536 Kb and comprising 8 exons. Recent studies have shown that TMEM200A can regulate adipose morphology by affecting adipogenesis ( 12 ). Tan et al ( 13 ) found that the expression of TMEM200A in familial pancreatic cancer was lower than in sporadic pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

High expression of TMEM200A is associated with a poor prognosis and immune infiltration in gastric cancer

Deng¹,

Li²,

Wei³

et al. 2023

Pathol. Oncol. Res.

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Background: Gastric cancer (GC) is one of the global malignant tumors with high incidence and poor prognosis. Exploring new GC molecular markers is important to improve GC prognosis. Transmembrane protein 200A (TMEM200A) is a member of the family of transmembrane proteins (TMEM). This study is the first to investigate the potential function of TMEM200A and its relationship with immune infiltration in GC.Methods: The differential expression of TMEM200A was determined through the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The receiver operating characteristic (ROC) curve was drawn to assess the diagnostic value of TMEM200A for GC. The relationship between TMEM200A and the clinical characteristics of patients with GC was investigated using the Wilcoxon test and the Kruskal-Wallis test. The effect of TMEM200A on overall survival (OS) was identified using the Kaplan-Meier method, the Log-rank test, the univariate/multivariate Cox regression analysis, and the nomogram prediction model. The co-expressed genes and gene set enrichment analysis (GSEA) were used to explore the potential biological functions of TMEM200A. We used the Tumor Immune Estimation Resource (TIMER) database and the ssGSEA algorithm to estimate the relationship between TMEM200A and immune cell infiltration. Furthermore, we investigated the correlation of TMEM200A with immune checkpoint/immune cell surface markers using the TCGA-STAD data set. Finally, we identified prognosis-related methylation sites in TMEM200A using MethSurv.Results: TMEM200A was highly expressed in GC tissues. TMEM200A had a good diagnostic value for GC. High expression of TMEM200A may shorten the OS of GC patients and may be an independent risk factor for OS in GC patients. TMEM200A participates in the construction of a predictive model with a good predictive effect on the survival rate of GC patients at 1, 3, and 5 years. Co-expressed genes and GSEA indicated that TMEM200A may be an adhesion molecule closely associated with tumor invasion and metastasis. In addition, TMEM200A may be significantly associated with immune cell infiltration and immune checkpoint expression. We also found that TMEM200A contains three methylation sites associated with a poor prognosis.Conclusion: Upregulated TMEM200A may be a promising prognostic marker for GC and is closely associated with the tumor microenvironment (TME).

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A distribution-centered approach for analyzing human adipocyte size estimates and their association with obesity-related traits and mitochondrial function

et al. 2021

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Objective Cell diameter, area, and volume are established quantitative measures of adipocyte size. However, these different adipocyte sizing parameters have not yet been directly compared regarding their distributions. Therefore, the study aimed to investigate how these adipocyte size measures differ in their distribution and assessed their correlation with anthropometry and laboratory chemistry. In addition, we were interested to investigate the relationship between fat cell size and adipocyte mitochondrial respiratory chain capacity. Methods Subcutaneous and visceral histology-based adipocyte size estimates from 188 individuals were analyzed by applying a panel of parameters to describe the underlying cell population. Histology-based adipocyte diameter distributions were compared with adipocyte diameter distributions from collagenase digestion. Associations of mean adipocyte size with body mass index (BMI), glucose, HbA1C, blood lipids as well as mature adipocyte mitochondrial respiration were investigated. Results All adipocyte area estimates derived from adipose tissue histology were not normally distributed, but rather characterized by positive skewness. The shape of the size distribution depends on the adipocyte sizing parameter and on the method used to determine adipocyte size. Despite different distribution shapes histology-derived adipocyte area, diameter, volume, and surface area consistently showed positive correlations with BMI. Furthermore, associations between adipocyte sizing parameters and glucose, HbA1C, or HDL specifically in the visceral adipose depot were revealed. Increasing subcutaneous adipocyte diameter was negatively correlated with adipocyte mitochondrial respiration. Conclusions Despite different underlying size distributions, the correlation with obesity-related traits was consistent across adipocyte sizing parameters. Decreased mitochondrial respiratory capacity with increasing subcutaneous adipocyte diameter could display a novel link between adipocyte hypertrophy and adipose tissue function.

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Genome-Wide Association Study of Diabetogenic Adipose Morphology in the GENetics of Adipocyte Lipolysis (GENiAL) Cohort

Cited by 10 publications

References 37 publications

LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes

LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes

High expression of TMEM200A is associated with a poor prognosis and immune infiltration in gastric cancer

A distribution-centered approach for analyzing human adipocyte size estimates and their association with obesity-related traits and mitochondrial function

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