AI Article Synopsis

  • SMRT (Silencing Mediator of Retinoid and Thyroid Hormone Receptors) is a key nuclear corepressor that influences metabolic processes, but its specific role in adipocytes (fat cells) has been unclear due to mixed results from previous mouse studies.
  • Researchers created an adipocyte-specific SMRT knockout mouse model (adSMRT-/-) to better understand its function, discovering that the loss of SMRT in fat cells does not cause obesity, even on a high-fat diet.
  • However, the adSMRT-/- mice experienced significant issues with glucose tolerance and insulin sensitivity, along with increased pro-inflammatory responses in their adipose tissue, indicating that SMRT plays a critical role in balancing metabolic and inflammatory signals

Article Abstract

The Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) is a nuclear corepressor, regulating the transcriptional activity of many transcription factors critical for metabolic processes. While the importance of the role of SMRT in the adipocyte has been well-established, our comprehensive understanding of its in vivo function in the context of homeostatic maintenance is limited due to contradictory phenotypes yielded by prior generalized knockout mouse models. Multiple such models agree that SMRT deficiency leads to increased adiposity, although the effects of SMRT loss on glucose tolerance and insulin sensitivity have been variable. We therefore generated an adipocyte-specific SMRT knockout (adSMRT-/-) mouse to more clearly define the metabolic contributions of SMRT. In doing so, we found that SMRT deletion in the adipocyte does not cause obesity-even when mice are challenged with a high-fat diet. This suggests that adiposity phenotypes of previously described models were due to effects of SMRT loss beyond the adipocyte. However, an adipocyte-specific SMRT deficiency still led to dramatic effects on systemic glucose tolerance and adipocyte insulin sensitivity, impairing both. This metabolically deleterious outcome was coupled with a surprising immune phenotype, wherein most genes differentially expressed in the adipose tissue of adSMRT-/- mice were upregulated in pro-inflammatory pathways. Flow cytometry and conditioned media experiments demonstrated that secreted factors from knockout adipose tissue strongly informed resident macrophages to develop a pro-inflammatory, MMe (metabolically activated) phenotype. Together, these studies suggest a novel role for SMRT as an integrator of metabolic and inflammatory signals to maintain physiological homeostasis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478322PMC
http://dx.doi.org/10.1210/endocr/bqaa132DOI Listing

Publication Analysis

Top Keywords

adipose tissue
12
smrt
11
role smrt
8
smrt deficiency
8
effects smrt
8
smrt loss
8
glucose tolerance
8
insulin sensitivity
8
adipocyte-specific smrt
8
smrt regulates
4

Similar Publications

Mesenchymal Stromal Cell (MSC) Isolation and Induction of Acute and Replicative Senescence.

Methods Mol Biol

December 2024

Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Luigi Vanvitelli Campania University, Naples, Italy.

Mesenchymal stromal cells (MSCs) are a heterogeneous population of non-hematopoietic adult stem cells derived from the embryonic mesoderm. They possess self-renewal and multipotent differentiation capabilities, allowing them to give rise to mesodermal cell types, such as osteoblasts, chondroblasts, and adipocytes, as well as non-mesodermal cells, including neuron-like cells and endothelial cells. MSCs play a vital role in maintaining homeostasis across various tissues by facilitating tissue repair, immune regulation, and inflammatory response balance.

View Article and Find Full Text PDF

Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures.

View Article and Find Full Text PDF

While bioactive glasses (BaGs) have been studied mainly for bone applications, studies have also shown their potential for soft tissue engineering. Incorporating therapeutic ions, such as lithium (Li), strontium (Sr), and boron (B) into the BaGs, has been found to promote angiogenesis and wound healing. However, a systematic study on the impact of Li, Sr, B, and the other ions in the BaGs, has not been conducted on a wide range of cells.

View Article and Find Full Text PDF

Unlabelled: Glucose transporter 4 (GLUT4) expression on white adipocytes is critical for absorbing excess blood glucose, failure of which promotes hyperglycemia. Matrix metalloproteinases (MMPs) play a crucial role in remodeling the white adipose tissue (WAT) during obesity. MMPs have multiple protein substrates, and surprisingly, it is unknown if they can directly target GLUT4 on the adipocyte surface and impair glucose absorption.

View Article and Find Full Text PDF

Role of gut microbiota and in inflammatory bowel disease through immune-mediated synergistic actions.

World J Gastroenterol

December 2024

The Second Clinical Medical College, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China.

A recent study published in the , suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease (IBD), particularly Crohn's disease. In addition, that paper illustrates the effect of changes in the gut microbiota on IBD and points out that altered mesenteric adipose tissue caused by the gut microbiota and creeping fat lead to increased inflammation, which exacerbates IBD. Moreover, recent research has shown that the interaction between () and the gut microbiota is mediated through immune mechanisms, resulting in a synergistic impact on IBD.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!