Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors and comprise three different isoforms namely PPARα, PPARγ, and PPARβ/δ with PPARβ/δ being the predominant subtype in human keratinocytes. After binding with specific ligands, PPARs regulate gene expression, cell growth and differentiation, apoptosis, inflammatory responses, and tumorogenesis. PPARs also modulate a wide variety of skin functions including keratinocyte proliferation, epidermal barrier formation, wound healing, melanocyte proliferation, and sebum production. Recent studies have shown the importance of PPARs in the pathogenesis of many dermatological disorders. Clinical trials have suggested possible role of PPAR agonists in the management of various dermatoses ranging from acne vulgaris, psoriasis, hirsutism, and lipodystrophy to cutaneous malignancies including melanoma. This article is intended to be a primer for dermatologists in their understanding of clinical relevance of PPARs and PPAR agonists in dermatology therapeutics.
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Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with T2D and MASLD.
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January 2025
Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, United States of America. Electronic address:
Background & Aims: Lanifibranor is a pan-PPAR agonist that improves glucose/lipid metabolism and reverses steatohepatitis and fibrosis in adults with MASH. We tested its effect on insulin resistance at the level of different target tissues in relationship to change in intrahepatic triglyceride (IHTG) content.
Methods: This phase 2, single center, study randomized (1:1) 38 patients with T2D and MASLD to receive lanifibranor 800 mg or placebo for 24 weeks.
Neuroprotective role of mirabegron: Targeting beta-3 adrenergic receptors to alleviate ulcerative colitis-associated cognitive impairment.
Biomed Pharmacother
January 2025
Pharmacology, Toxicology and Biochemistry Department, Faculty of Pharmacy, Future University in Egypt (FUE), Cairo, Egypt; Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
While cognitive impairment has been documented in ulcerative colitic patients, the possible influence of central β3-adrenergic receptor (β3-AR) signaling on this extraintestinal manifestation remains unclear. Previously, we identified an imperative role for mirabegron (MA) as an agonist of β3-AR, in decreasing the BACE-1/beta-amyloid (Aβ) cue in the colons of UC rats. Consequently, we investigated its therapeutic potential for alleviating cognitive impairment associated with UC.
View Article and Find Full Text PDFThe pan-PPAR agonist lanifibranor reduces portal pressure independent of fibrosis reduction through the splanchnic vasculature.
Biomed Pharmacother
January 2025
Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium; Liver Research Center Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium. Electronic address:
Portal hypertension (PH) can cause severe complications in patients with advanced chronic liver disease (aCLD). The pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor reduces portal pressure in preclinical models of aCLD. Since the effect on PH might be secondary to fibrosis improvement, we investigated the effect of lanifibranor on PH, hepatic and splanchnic angiogenesis in mouse models of fibrotic and prehepatic non-fibrotic PH.
View Article and Find Full Text PDFEffects of radiotherapy on the hippocampus and hippocampal neurogenesis: a systematic review of preclinical studies.
Strahlenther Onkol
January 2025
Department of Radiation Medicine, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA.
Purpose: A comprehensive literature review was undertaken to understand the effects and underlying mechanisms of cranial radiotherapy (RT) on the hippocampus and hippocampal neurogenesis as well as to explore protective factors and treatments that might mitigate these effects in preclinical studies.
Methods: PubMed/MEDLINE, Web of Science, and Embase were queried for studies involving the effects of radiation on the hippocampus and hippocampal neurogenesis. Data extraction followed the Animal Research Reporting of In Vivo Experiments (ARRIVE) guidelines, and a risk of bias assessment was conducted for the included animal studies using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool.
Lifestyle and Pharmacologic Approaches to Prevention of MASLD-related HCC.
Clin Gastroenterol Hepatol
January 2025
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address:
Hepatocellular carcinoma (HCC) is a major concern for public health. Fatty liver disease, related to alcohol misuse or metabolic syndrome, has become the leading cause of chronic liver disease and HCC. The strong association between type 2 diabetes mellitus and HCC can be partly attributed to the development of metabolic dysfunction associated steatotic liver disease (MASLD).
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