Summary of Study ST002268
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001450. The data can be accessed directly via it's Project DOI: 10.21228/M89703 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002268 |
| Study Title | Autophagy-related protein PIK3C3 maintains healthy brown and white adipose tissues to prevent metabolic diseases |
| Study Type | Lipidomics |
| Study Summary | Adequate mass and function of adipose tissues (ATs) play an essential role in preventing metabolic perturbations. Pathological reduction of ATs in lipodystrophy leads to an array of metabolic diseases. Understanding the underlying mechanisms may benefit the development of effective therapies. Several cellular processes, including autophagy, function collectively to maintain AT homeostasis. Here, we investigated the impact of adipocyte-specific deletion of the autophagy-related lipid kinase PIK3C3 on AT homeostasis and systemic metabolism in mice. We report that PIK3C3 functions in all ATs and that its absence disturbs adipocyte autophagy and hinders adipocyte differentiation, survival, and function with differential effects on brown and white ATs. These abnormalities caused loss of white ATs, whitening followed by loss of brown ATs, and impaired browning of white ATs. Consequently, mice exhibited compromised thermogenic capacity and developed dyslipidemia, hepatic steatosis, insulin resistance and type 2 diabetes. While these effects of PIK3C3 contrast previous findings with the autophagy-related protein ATG7 in adipocytes, mice with a combined deficiency in both factors revealed a dominant role of the PIK3C3-deficient phenotype. We also found that dietary lipid excess exacerbates AT pathologies caused by PIK3C3 deficiency. Surprisingly, glucose tolerance was spared in adipocyte-specific PIK3C3-deficient mice, a phenotype that was more evident during dietary lipid excess. These findings reveal a crucial yet complex role for PIK3C3 in ATs and suggest the potential of targeting this factor for therapeutic intervention in metabolic diseases. |
| Institute | Vanderbilt University |
| Department | Chemistry |
| Laboratory | Center for Innovative Technology |
| Last Name | Leaptrot |
| First Name | Katrina |
| Address | 1234 Stevenson Center Ln |
| katrina.l.leaptrot@vanderbilt.edu | |
| Phone | 6158758422 |
| Submit Date | 2022-08-26 |
| Num Groups | 4 |
| Total Subjects | 16 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-02-26 |
| Release Version | 1 |
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Project:
| Project ID: | PR001450 |
| Project DOI: | doi: 10.21228/M89703 |
| Project Title: | Autophagy-related protein PIK3C3 maintains healthy brown and white adipose tissues to prevent metabolic diseases |
| Project Type: | Lipidomics |
| Project Summary: | Adequate mass and function of adipose tissues (ATs) play an essential role in preventing metabolic perturbations. Pathological reduction of ATs in lipodystrophy leads to an array of metabolic diseases. Understanding the underlying mechanisms may benefit the development of effective therapies. Several cellular processes, including autophagy, function collectively to maintain AT homeostasis. Here, we investigated the impact of adipocyte-specific deletion of the autophagy-related lipid kinase PIK3C3 on AT homeostasis and systemic metabolism in mice. We report that PIK3C3 functions in all ATs and that its absence disturbs adipocyte autophagy and hinders adipocyte differentiation, survival, and function with differential effects on brown and white ATs. These abnormalities caused loss of white ATs, whitening followed by loss of brown ATs, and impaired browning of white ATs. Consequently, mice exhibited compromised thermogenic capacity and developed dyslipidemia, hepatic steatosis, insulin resistance and type 2 diabetes. While these effects of PIK3C3 contrast previous findings with the autophagy-related protein ATG7 in adipocytes, mice with a combined deficiency in both factors revealed a dominant role of the PIK3C3-deficient phenotype. We also found that dietary lipid excess exacerbates AT pathologies caused by PIK3C3 deficiency. Surprisingly, glucose tolerance was spared in adipocyte-specific PIK3C3-deficient mice, a phenotype that was more evident during dietary lipid excess. These findings reveal a crucial yet complex role for PIK3C3 in ATs and suggest the potential of targeting this factor for therapeutic intervention in metabolic diseases. |
| Institute: | Vanderbilt University |
| Department: | Chemistry |
| Laboratory: | Center for Innovative Technology |
| Last Name: | Leaptrot |
| First Name: | Katrina |
| Address: | 1234 Stevenson Center Ln |
| Email: | katrina.l.leaptrot@vanderbilt.edu |
| Phone: | 6158758422 |
