3rd Edition of Diabetes and Endocrinology World Conference 2027
Speakers - dewc 2027
Prashant Dubey
Prashant Dubey
- Designation: Jamia Hamdard University
- Country: India
- Title: Inflammatory and Metabolic Alterations Driven Female Specific Chronic Pancreatitis
Abstract
Introduction
Metabolic endotoxemia associated with chronic high fat diet HFD intake and low grade lipopolysaccharide LPS exposure is a key driver of pancreatic inflammation, fibrosis, and endocrine dysfunction. Excess lipid availability and LPS activate Toll like receptor 4 TLR4 signaling, promoting macrophage infiltration, inflammatory cytokine release, and fibrogenic remodeling of pancreatic tissue. Emerging evidence indicates that sex hormones, particularly estradiol, critically modulate immune and metabolic responses; however, sex specific pancreatic adaptations to HFD induced metabolic inflammation remain poorly understood. In the present study, we investigated inflammatory, fibrotic, metabolic, and hormonal alterations in the pancreas of male and female Wistar rats subjected to chronic HFD feeding followed by LPS exposure.
Results
Chronic HFD combined with LPS induced a pronounced sex dependent pancreatic response. Female rats exhibited significant upregulation of inflammatory markers Toll like receptor 4 Tlr4, C reactive protein Crp, along with macrophage infiltration markers Cluster of Differentiation 11b Cd11b and Cluster of Differentiation 68 Cd68. This inflammatory activation was accompanied by robust induction of fibrotic markers Collagen Type I Alpha 1 Chain Col1a1, Alpha Smooth Muscle Actin alpha SMA, Endothelin 1 Edn1, and Fibrillin Fbn, indicating extensive fibrogenic remodeling of pancreatic tissue. These molecular alterations were associated with a significant elevation in serum lipase levels, confirming exocrine pancreatic injury, and a marked reduction in circulating insulin levels, reflecting beta cell dysfunction in LPS treated females. Notably, serum estradiol levels were significantly decreased in female rats following chronic LPS exposure with HFD, suggesting impaired estrogen mediated protection during metabolic inflammation.
In contrast, male rats showed minimal induction of inflammatory and fibrotic genes, with negligible changes in Tlr4 and Crp expression. Serum insulin levels remained unchanged, indicating preserved endocrine function. Importantly, circulating estradiol levels in males were not significantly altered following HFD and LPS exposure. Additionally, Apolipoprotein C II Apoc2 expression was significantly upregulated in males but downregulated in females, suggesting a sex specific metabolic adaptation to lipid overload that may contribute to pancreatic resilience in males.
Conclusion
The present study demonstrates that chronic HFD with LPS exposure induces severe pancreatic inflammation, fibrosis, and endocrine dysfunction in female rats, while males exhibit relative resistance to inflammatory remodeling and maintain pancreatic endocrine homeostasis. The selective decline in estradiol levels in females may exacerbate TLR4 driven immune activation and fibrogenic signaling, thereby amplifying pancreatic injury under metabolic endotoxemia. In contrast, preserved estradiol levels and enhanced APOC2 mediated lipid handling in males may confer protection against pancreatic inflammation. These findings underscore the critical role of sex hormones in shaping pancreatic responses to metabolic stress and emphasize the importance of considering sex as a biological variable in obesity associated pancreatitis and therapeutic strategy development.
Metabolic endotoxemia associated with chronic high fat diet HFD intake and low grade lipopolysaccharide LPS exposure is a key driver of pancreatic inflammation, fibrosis, and endocrine dysfunction. Excess lipid availability and LPS activate Toll like receptor 4 TLR4 signaling, promoting macrophage infiltration, inflammatory cytokine release, and fibrogenic remodeling of pancreatic tissue. Emerging evidence indicates that sex hormones, particularly estradiol, critically modulate immune and metabolic responses; however, sex specific pancreatic adaptations to HFD induced metabolic inflammation remain poorly understood. In the present study, we investigated inflammatory, fibrotic, metabolic, and hormonal alterations in the pancreas of male and female Wistar rats subjected to chronic HFD feeding followed by LPS exposure. x as a biological variable in obesity associated pancreatitis and therapeutic strategy development.
Welcome to the 3rd Edition of Diabetes and Endocrinology World Conference (DEWC) 2027
DEWC 2027 is a top- ...
Read More>>
Organizer
