Maintenance of thermogenic adipose tissues despite loss of the H3K27 acetyltransferases p300 or CBP

Aug 14, 2024American journal of physiology. Endocrinology and metabolism

Thermogenic fat tissues remain active despite losing the enzymes p300 or CBP that modify gene activity

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Loss of either p300 or CBP in mice does not affect brown adipose tissue mass or thermogenic marker expression.

Brown and beige adipose tissues play a key role in energy balance and thermogenesis in mice.
p300 and CBP are histone acetyltransferases that typically facilitate transcriptional activation through H3K27ac marks.
Knockout of p300 or CBP was confirmed, yet brown adipose tissue remained unaffected in terms of mass and thermogenic function.
Mice lacking p300 or CBP showed similar weight gain and glucose intolerance on a high-fat diet as control mice.
The response to the β-adrenergic agonist CL-316,243, which induces browning of white fat, was largely preserved in knockout mice.
These findings suggest that p300 and CBP may have compensatory roles in thermogenic fat, allowing for resilience against their individual loss.

AI simplified

Brown and beige adipose tissues are specialized for thermogenesis and are important for energy balance in mice. Mounting evidence suggests that chromatin-modifying enzymes are integral for the development, maintenance, and functioning of thermogenic adipocytes. p300 and cAMP-response element binding protein (CREB)-binding protein (CBP) are histone acetyltransferases (HATs) responsible for writing the transcriptionally activating mark H3K27ac. Despite their homology, p300 and CBP do have unique tissue- and context-dependent roles, which have yet to be examined in brown and beige adipocytes specifically. We assessed the requirement of p300 or CBP in thermogenic fat using uncoupling protein 1 ()Cre-mediated knockdown in mice to determine whether their loss impacted tissue development, susceptibility to diet-induced obesity, and response to pharmacological induction via β-agonism. Despite successful knockdown, brown adipose tissue mass and expression of thermogenic markers were unaffected by loss of either HAT. As such, knockout mice developed a comparable degree of diet-induced obesity and glucose intolerance to that of floxed controls. Furthermore, "browning" of white adipose tissue by the β-adrenergic agonist CL-316,243 remained largely intact in knockout mice. Although p300 and CBP have nonoverlapping roles in other tissues, our results indicate that they are individually dispensable within thermogenic fats specifically, possibly due to functional compensation by one another.The role of transcriptionally activating H3K27ac epigenetic mark has yet to be examined in mouse thermogenic fats specifically, which we achieved here via-Cre-driven knockdown of the histone acetyltransferases (HAT) p300 or CBP under several metabolic contexts. Despite successful knockdown of either HAT, brown adipose tissue was maintained at room temperature. As such, knockout mice were indistinguishable to controls when fed an obesogenic diet or when given a β-adrenergic receptor agonist to induce browning of white fat. Unlike other tissues, thermogenic fats are resilient to p300 or CBP ablation, likely due to sufficient functional overlap between them. Ucp1 -Ucp1 3 3 3NEW & NOTEWORTHY

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text ↗

Maintenance of thermogenic adipose tissues despite loss of the H3K27 acetyltransferases p300 or CBP

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief