Aging is accompanied by major changes in adipose tissue distribution and function. In particular, with time, thermogenic-competent beige adipocytes progressively gain a white adipocyte morphology. However, the mechanisms controlling the age-related transition of beige adipocytes to white adipocytes remain unclear. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser enzyme positively regulating differentiation and function of adipocytes. Here we show that Lsd1 levels decrease in aging inguinal white adipose tissue concomitantly with beige fat cell decline. Accordingly, adipocyte-specific increase of Lsd1 expression is sufficient to rescue the age-related transition of beige adipocytes to white adipocytes in vivo, whereas loss of Lsd1 precipitates it. Lsd1 maintains beige adipocytes by controlling the expression of peroxisome proliferator-activated receptor α (Ppara), and treatment with a Ppara agonist is sufficient to rescue the loss of beige adipocytes caused by Lsd1 ablation. In summary, our data provide insights into the mechanism controlling the age-related beige-to-white adipocyte transition and identify Lsd1 as a regulator of beige fat cell maintenance.
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http://dx.doi.org/10.1073/pnas.1702641114 | DOI Listing |
Life Sci
January 2025
Université Côte d'Azur, CNRS, Inserm, Adipo-Cible Research Study Group, iBV, Nice, France. Electronic address:
Aims: Thermogenic adipocytes are able to dissipate energy as heat from lipids and carbohydrates through enhanced uncoupled respiration, due to UCP1 activity. PPAR family of transcription factors plays an important role in adipocyte biology. The purpose of this work was to characterize the role of PPARα and pemafibrate in the control of thermogenic adipocyte formation and function.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Holman Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New Science Building, 435 E 30(th) Street, New York, NY, 10016, USA. Electronic address:
It has been well established that adenosine plays a key role in the control of inflammation through G protein coupled receptors and recently shown that it can regulate thermogenesis. Here we investigated the specific requirements of the adenosine A2A receptor (A2AR) in mature adipocytes for thermogenic functionality and metabolic homeostasis. We generated fat tissue specific adenosine A2A receptor knock-out mice to assess the influence of signaling through this receptor on brown and beige fat functionality, obesity, insulin sensitivity, inflammation and liver function.
View Article and Find Full Text PDFSci China Life Sci
January 2025
Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Skeletal muscle plays a significant role in both local and systemic energy metabolism. The current investigation aims to explore the role of the Bambi gene in skeletal muscle, focusing on its implications for muscle hypertrophy and systemic metabolism. We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy, improves metabolic performance, and activates thermogenic adipocytes via the reprogramming of progenitor of iWAT, offering potential therapeutic strategies for metabolic syndromes.
View Article and Find Full Text PDFSTAR Protoc
January 2025
School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address:
White adipose tissue (WAT) beiging holds significant therapeutic potential for combating obesity. Here, we present a protocol for inducing beige WAT in mice using both cold exposure and CL316,243 treatment. We describe steps for intraperitoneal injection, and subcutaneous WAT (sWAT) isolation, dissection, and fixation.
View Article and Find Full Text PDFCurr Obes Rep
January 2025
Maine Medical Center Research Institute, Maine Medical Center, 81 Research Drive, Scarborough, ME, 04074, USA.
Purpose Of Review: Bone marrow adipose tissue is a distinctive fat depot located within the skeleton, with the potential to influence both local and systemic metabolic processes. Although significant strides have been made in understanding bone marrow adipose tissue over the past decade, many questions remain regarding their precise lineage and functional roles.
Recent Findings: Recent studies have highlighted bone marrow adipose tissue's involvement in continuous cross-talk with other organs and systems, exerting both endocrine and paracrine functions that play a crucial role in metabolic homeostasis, skeletal remodeling, hematopoiesis, and the progression of bone metastases.
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