Year: 2025
Type: article
Abstract: Disclosure: M. Fathali: None. T. Mackie: None. A. Bitto: None. Objective: Adefovir dipivoxil (ADV) promotes the expression of CCAAT-enhancer-binding protein-β (C/EBPβ) target genes that are involved in fatty acid oxidation. Furthermore, ADV treatment reduces diet-induced obesity in mice, though the mechanisms are currently unclear. Free fatty acids are toxic to pancreatic β cells and thus important in the development of type 2 diabetes mellitus. We hypothesize that ADV can protect against fatty acid toxicity in pancreatic β cell lines and increase insulin secretion through mitohormesis. Approach: Immortalized β cells were treated with ADV and palmitic acid and evaluated for toxicity and mitochondrial function via flow cytometry, insulin secretion via ELISA, mitochondrial DNA copy number via qPCR, and mitochondrial morphology via microscopy (no palmitate was given with this method). Results: We found that insulin secretion was increased in cells treated with ADV at all concentrations compared to those without ADV treatment at no palmitate levels. Our research also revealed that ADV protects against fatty acid toxicity, with the least amount of cell death seen in cells treated with ADV compared to those without ADV treatment at maximum palmitate concentrations. Finally, we found that mitochondrial function, as quantified by TMRE fluorescence to MitoTracker Deep Red fluorescence ratio, was highest in cells treated with ADV at all concentrations compared to those without ADV treatment, regardless of palmitate concentrations. Data from qPCR and microscopy of mitochondria are currently pending. Conclusions: These data show that ADV can protect against fatty acid toxicity and increase insulin secretion in pancreatic β cells, potentially through mitohormesis. This drug can elucidate the role of mitochondria in the pathogenesis of type 2 diabetes mellitus, which may lead to new understandings and therapeutic approaches. Presentation: Sunday, July 13, 2025
Source: Journal of the Endocrine Society
Authors: Maha Fathali, Timothy Mackie, Alessandro Bitto
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,255
OpenAlex ID: W4415453763
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