Gestational diabetes mellitus (GDM) is associated with increased inflammation in adipose tissues. Fibroblast growth factor 21 (FGF21) is an endocrine hormone which signals to multiple tissues to regulate metabolism. However, its role in GDM remains largely unknown. In this study, we found that impaired FGF21 signaling in GDM correlates with worsened inflammation and insulin resistance in white adipose tissues in mice. Mechanistically, the pregnancy-related upregulation of FGF21 signaling in adipocytes promotes the differentiation of regulatory T cells (Tregs), which are critical for reducing pregnancy-induced adipose tissue inflammation. The anti-inflammatory effects of FGF21 may involve linolenic acid-mediated PGE2 synthesis in adipocytes. These findings underscore FGF21's role in mediating crosstalk between mature adipocytes and immune cells in white adipose tissue and suggest that targeting FGF21 signaling and its downstream metabolites could offer a potential therapeutic approach for GDM in humans.
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http://dx.doi.org/10.3390/nu16223826 | DOI Listing |
J Cell Mol Med
December 2024
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Mitochondrial dysfunction is a key event in many pathological conditions, including neurodegenerative processes. When mitochondria are damaged, they release damage-associated molecular patterns (DAMPs) that activate mito-inflammation. The present study assessed mito-inflammation after in vitro oxygen-glucose deprivation as a representation of ischaemia, followed by reoxygenation (OGD/R) of HT22 cells and modulation of the inflammatory response by melatonin.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, 21 Sassoon Road, Pokfulam 999077, Hong Kong, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam 999077, Hong Kong, China; Department of Pharmacology and Pharmacy, The University of Hong Kong, 21 Sassoon Road, Pokfulam 999077, Hong Kong, China. Electronic address:
β-Klotho (KLB), a type I transmembrane protein, serves as an obligate co-receptor determining the tissue-specific actions of endocrine fibroblast growth factors (FGFs). Despite accumulative evidence suggesting the occurrence of N-glycosylation in the KLB protein, the precise N-glycosites, glycoforms, and the impacts of N-glycosylation on the expression and function of the KLB protein remain unexplored. Employing a mass spectrometry-based approach, a total of 12 N-glycosites displaying heterogeneous site occupancy and glycoforms were identified within the extracellular region of the recombinant human KLB protein.
View Article and Find Full Text PDFEcotoxicol Environ Saf
December 2024
Spinal surgery, China-Japan Friendship Hospital, East Ying Hua Yuan Street, Chaoyang District, Beijing, China.
Heatstroke (HS) is gradually becoming a major challenge in the field of global public health with the trend of global warming. In recent years, extreme high-temperature weather events have occurred frequently in the world, which directly led to a significant increase in heatstroke. However, up to now, the potential pathological effects of HS on articular cartilage have not been revealed.
View Article and Find Full Text PDFAppl Biochem Biotechnol
December 2024
Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, 111 Ren'ai Road, SD334F, Suzhou, 215123, Jiangsu, China.
Non-alcoholic steatohepatitis (NASH) is a potential serious disease, which almost has no available medicine for effective treatment today. Efruxifermin is a bivalent Fc-FGF21 candidate drug developed by Akero Therapeutics that has shown promising results in preclinical and clinical trials for NASH and may be approved in future. However, it is produced by Escherichia coli (E.
View Article and Find Full Text PDFNutrients
November 2024
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.
Background: The ketogenic diet (KD) is a widely used intervention for obesity and diabetes, effectively reducing body weight and blood glucose levels. However, the molecular mechanisms by which the KD influences body weight and glucose metabolism are not fully understood. While previous research has shown that the KD affects the gut microbiota, the exact role of microbiota in mediating its metabolic effects remains unclear.
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