Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model
Adipose tissue (AT) is no longer considered to be responsible for energy storage only but is now recognized as a major endocrine organ that is distributed across different parts of the body and is actively involved in regulatory processes controlling energy homeostasis. Moreover, AT plays a crucial...
Guardado en:
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/5ec696238cf646458e2740e49369e5db |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:5ec696238cf646458e2740e49369e5db |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:5ec696238cf646458e2740e49369e5db2021-11-30T12:35:44ZDifferential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model2296-858X10.3389/fmed.2021.751277https://doaj.org/article/5ec696238cf646458e2740e49369e5db2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.751277/fullhttps://doaj.org/toc/2296-858XAdipose tissue (AT) is no longer considered to be responsible for energy storage only but is now recognized as a major endocrine organ that is distributed across different parts of the body and is actively involved in regulatory processes controlling energy homeostasis. Moreover, AT plays a crucial role in the development of metabolic disease such as diabetes. Recent evidence has shown that adipokines have the ability to regulate blood glucose levels and improve metabolic homeostasis. While AT has been studied extensively in the context of type 2 diabetes, less is known about how different AT types are affected by absolute insulin deficiency in type 1 or permanent neonatal diabetes mellitus. Here, we analyzed visceral and subcutaneous AT in a diabetic, insulin-deficient pig model (MIDY) and wild-type (WT) littermate controls by RNA sequencing and quantitative proteomics. Multi-omics analysis indicates a depot-specific dysregulation of crucial metabolic pathways in MIDY AT samples. We identified key proteins involved in glucose uptake and downstream signaling, lipogenesis, lipolysis and β-oxidation to be differentially regulated between visceral and subcutaneous AT in response to insulin deficiency. Proteins related to glycogenolysis, pyruvate metabolism, TCA cycle and lipogenesis were increased in subcutaneous AT, whereas β-oxidation-related proteins were increased in visceral AT from MIDY pigs, pointing at a regionally different metabolic adaptation to master energy stress arising from diminished glucose utilization in MIDY AT. Chronic, absolute insulin deficiency and hyperglycemia revealed fat depot-specific signatures using multi-omics analysis. The generated datasets are a valuable resource for further comparative and translational studies in clinical diabetes research.Florian FlenkenthalerFlorian FlenkenthalerErik LändströmErik LändströmBachuki ShashikadzeMattias BackmanMattias BackmanAndreas BlutkeJulia Philippou-MassierJulia Philippou-MassierSimone RennerSimone RennerSimone RennerMartin Hrabe de AngelisMartin Hrabe de AngelisRüdiger WankeHelmut BlumGeorg J. ArnoldEckhard WolfEckhard WolfEckhard WolfEckhard WolfThomas FröhlichFrontiers Media S.A.articlediabetesinsulin deficiencyadipose tissueproteometranscriptomepig modelMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
diabetes insulin deficiency adipose tissue proteome transcriptome pig model Medicine (General) R5-920 |
| spellingShingle |
diabetes insulin deficiency adipose tissue proteome transcriptome pig model Medicine (General) R5-920 Florian Flenkenthaler Florian Flenkenthaler Erik Ländström Erik Ländström Bachuki Shashikadze Mattias Backman Mattias Backman Andreas Blutke Julia Philippou-Massier Julia Philippou-Massier Simone Renner Simone Renner Simone Renner Martin Hrabe de Angelis Martin Hrabe de Angelis Rüdiger Wanke Helmut Blum Georg J. Arnold Eckhard Wolf Eckhard Wolf Eckhard Wolf Eckhard Wolf Thomas Fröhlich Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model |
| description |
Adipose tissue (AT) is no longer considered to be responsible for energy storage only but is now recognized as a major endocrine organ that is distributed across different parts of the body and is actively involved in regulatory processes controlling energy homeostasis. Moreover, AT plays a crucial role in the development of metabolic disease such as diabetes. Recent evidence has shown that adipokines have the ability to regulate blood glucose levels and improve metabolic homeostasis. While AT has been studied extensively in the context of type 2 diabetes, less is known about how different AT types are affected by absolute insulin deficiency in type 1 or permanent neonatal diabetes mellitus. Here, we analyzed visceral and subcutaneous AT in a diabetic, insulin-deficient pig model (MIDY) and wild-type (WT) littermate controls by RNA sequencing and quantitative proteomics. Multi-omics analysis indicates a depot-specific dysregulation of crucial metabolic pathways in MIDY AT samples. We identified key proteins involved in glucose uptake and downstream signaling, lipogenesis, lipolysis and β-oxidation to be differentially regulated between visceral and subcutaneous AT in response to insulin deficiency. Proteins related to glycogenolysis, pyruvate metabolism, TCA cycle and lipogenesis were increased in subcutaneous AT, whereas β-oxidation-related proteins were increased in visceral AT from MIDY pigs, pointing at a regionally different metabolic adaptation to master energy stress arising from diminished glucose utilization in MIDY AT. Chronic, absolute insulin deficiency and hyperglycemia revealed fat depot-specific signatures using multi-omics analysis. The generated datasets are a valuable resource for further comparative and translational studies in clinical diabetes research. |
| format |
article |
| author |
Florian Flenkenthaler Florian Flenkenthaler Erik Ländström Erik Ländström Bachuki Shashikadze Mattias Backman Mattias Backman Andreas Blutke Julia Philippou-Massier Julia Philippou-Massier Simone Renner Simone Renner Simone Renner Martin Hrabe de Angelis Martin Hrabe de Angelis Rüdiger Wanke Helmut Blum Georg J. Arnold Eckhard Wolf Eckhard Wolf Eckhard Wolf Eckhard Wolf Thomas Fröhlich |
| author_facet |
Florian Flenkenthaler Florian Flenkenthaler Erik Ländström Erik Ländström Bachuki Shashikadze Mattias Backman Mattias Backman Andreas Blutke Julia Philippou-Massier Julia Philippou-Massier Simone Renner Simone Renner Simone Renner Martin Hrabe de Angelis Martin Hrabe de Angelis Rüdiger Wanke Helmut Blum Georg J. Arnold Eckhard Wolf Eckhard Wolf Eckhard Wolf Eckhard Wolf Thomas Fröhlich |
| author_sort |
Florian Flenkenthaler |
| title |
Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model |
| title_short |
Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model |
| title_full |
Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model |
| title_fullStr |
Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model |
| title_full_unstemmed |
Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model |
| title_sort |
differential effects of insulin-deficient diabetes mellitus on visceral vs. subcutaneous adipose tissue—multi-omics insights from the munich midy pig model |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/5ec696238cf646458e2740e49369e5db |
| work_keys_str_mv |
AT florianflenkenthaler differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT florianflenkenthaler differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT eriklandstrom differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT eriklandstrom differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT bachukishashikadze differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT mattiasbackman differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT mattiasbackman differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT andreasblutke differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT juliaphilippoumassier differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT juliaphilippoumassier differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT simonerenner differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT simonerenner differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT simonerenner differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT martinhrabedeangelis differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT martinhrabedeangelis differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT rudigerwanke differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT helmutblum differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT georgjarnold differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT eckhardwolf differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT eckhardwolf differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT eckhardwolf differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT eckhardwolf differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel AT thomasfrohlich differentialeffectsofinsulindeficientdiabetesmellitusonvisceralvssubcutaneousadiposetissuemultiomicsinsightsfromthemunichmidypigmodel |
| _version_ |
1718406565043634176 |