Good news! However, the news release and the research article are horribly written!
"Scientists ... have discovered a key biological reason why obesity increases the risk of Type 2 diabetes, and it boils down to size — specifically the size of fat cells. ..."
"Key takeaways
- Fat tissue stores energy from food and is crucial for maintaining normal glucose metabolism, but doesn’t function properly in obesity when fat cells become enlarged.
- Scientists ... have pinpointed at a molecular level how obesity causes fat cells to become enlarged. The answer lies in fat stem cells that don’t produce essential cellular building blocks called ribosomal factors, preventing the cells’ ability to make new fat cells.
- Restoring ribosomal factors triggers the fat stem cells to differentiate to produce new, better and smaller fat cells, improving glucose metabolism and Type 2 diabetes symptoms.
...
Without sufficient ribosomal factors, fat stem cells lack the machinery to differentiate to produce functioning fat cells. Instead, energy gets trapped and they become enlarged. ...
When obese, diabetic mice — whose fat cells were four to five times larger than those found in lean mice — were given a drug called rosiglitazone, their ribosomal factors increased to normal levels, which triggered their fat stem cells to differentiate to produce new, smaller fat cells. The fat tissue, in turn, was then able to function properly in storing energy and generating key hormones that regulate metabolism. ...
The findings ... establishing for the first time that obesity limits the body’s ability to produce crucial cellular building blocks called ribosomal factors.
When obese, diabetic mice — whose fat cells were four to five times larger than those found in lean mice — were given a drug called rosiglitazone, their ribosomal factors increased to normal levels, which triggered their fat stem cells to differentiate to produce new, smaller fat cells. The fat tissue, in turn, was then able to function properly in storing energy and generating key hormones that regulate metabolism. ...
Rosiglitazone is currently being used to treat Type 2 diabetes, but what hasn’t been clear, until now, is what the drug is doing on a molecular level to improve glucose metabolism. ..."
From the highlights and abstract (not easy to understand unless you are a specialist in the field):
"Highlights
• Single-cell RNA sequencing reveals reprogramming of adipocyte precursors
• PPARγ agonist stimulates ribosomal gene expression in adipocyte precursors in obesity
• Polysome profiling of adipocytes shows translational selectivity of mRNAs
• Inhibition of translation with eIF4A inhibitor blocks adipogenesis
Summary
Adipose tissue regulates energy homeostasis and metabolic function, but its adaptability is impaired in obesity. In this study, we investigate the impact of acute PPARγ agonist treatment in obese mice and find significant transcriptional remodeling of cells in the stromal vascular fraction (SVF). Using single-cell RNA sequencing, we profile the SVF of inguinal and epididymal adipose tissue of obese mice following rosiglitazone treatment and find an induction of ribosomal factors in both progenitor and preadipocyte populations, while expression of ribosomal factors is reduced with obesity. Notably, the expression of a subset of ribosomal factors is directly regulated by PPARγ. Polysome profiling of the epididymal SVF shows that rosiglitazone promotes translational selectivity of mRNAs that encode pathways involved in adipogenesis and lipid metabolism. Inhibition of translation using a eukaryotic translation initiation factor 4A (eIF4A) inhibitor is sufficient in blocking adipogenesis. Our findings shed light on how PPARγ agonists promote adipose tissue plasticity in obesity."
PPARγ-dependent remodeling of translational machinery in adipose progenitors is impaired in obesity (open access)
Graphical abstract
No comments:
Post a Comment