Palmitate-Induced Lipotoxicity Triggers ER Stress Without Increasing ROS in β Cells
Abstract
Obesity has become a widespread health concern in the United States, steadily increasing across all demographics since 1999. This rise is largely attributed to the typical Western diet, high in fat and fructose, combined with genetic predispositions identified through genome-wide association studies (GWAS) that link specific variants to an elevated risk of obesity. The accumulation of excess adipose tissue raises circulating free fatty acid (FFA) levels, which, when inadequately cleared, lead to lipotoxicity (LT). Elevated FFAs interfere with insulin signaling, causing insulin resistance and resulting in high plasma glucose levels, a condition known as glucotoxicity (GT). Together, these processes, referred to as glucolipotoxicity (GLT), create a cellular environment that increases susceptibility to type 2 diabetes (T2D). Understanding how GLT impacts pancreatic β-cell function is essential for advancing prevention and treatment strategies. To investigate this, we examined how prolonged exposure to FFAs affects β-cell homeostasis, focusing on the endoplasmic reticulum (ER) and its interaction with mitochondria. INS1 cells treated with 200 µM palmitic acid (PA) for 24 hours showed increased intracellular proinsulin levels relative to controls, but total insulin content was markedly decreased, indicating possible defects in proinsulin processing or secretion. BiP expression was also elevated in PA-treated cells, suggesting the onset of ER stress. Because ER and mitochondria work closely to maintain cellular homeostasis, we next asked whether mitochondrial health was affected during LT. However, our measurement of reactive oxygen species (ROS) using the DCF assay revealed no significant differences between control and PA-treated groups, suggesting that mitochondrial oxidative stress was not prominent under these conditions. Overall, these findings indicate that lipotoxic stress primarily disrupts ER homeostasis and insulin maturation in β cells, potentially representing an early adaptive response to FFA-induced stress before overt mitochondrial or protein-folding defects occur.
Start Time
15-4-2026 9:00 AM
End Time
15-4-2026 12:00 PM
Room Number
Culp Ballroom 316
Poster Number
42
Presentation Type
Poster
Presentation Subtype
Posters - Competitive
Presentation Category
Science, Technology, and Engineering
Student Type
Graduate and Professional Degree Students, Residents, Fellows
Faculty Mentor
Anoop Arunagiri
Palmitate-Induced Lipotoxicity Triggers ER Stress Without Increasing ROS in β Cells
Culp Ballroom 316
Obesity has become a widespread health concern in the United States, steadily increasing across all demographics since 1999. This rise is largely attributed to the typical Western diet, high in fat and fructose, combined with genetic predispositions identified through genome-wide association studies (GWAS) that link specific variants to an elevated risk of obesity. The accumulation of excess adipose tissue raises circulating free fatty acid (FFA) levels, which, when inadequately cleared, lead to lipotoxicity (LT). Elevated FFAs interfere with insulin signaling, causing insulin resistance and resulting in high plasma glucose levels, a condition known as glucotoxicity (GT). Together, these processes, referred to as glucolipotoxicity (GLT), create a cellular environment that increases susceptibility to type 2 diabetes (T2D). Understanding how GLT impacts pancreatic β-cell function is essential for advancing prevention and treatment strategies. To investigate this, we examined how prolonged exposure to FFAs affects β-cell homeostasis, focusing on the endoplasmic reticulum (ER) and its interaction with mitochondria. INS1 cells treated with 200 µM palmitic acid (PA) for 24 hours showed increased intracellular proinsulin levels relative to controls, but total insulin content was markedly decreased, indicating possible defects in proinsulin processing or secretion. BiP expression was also elevated in PA-treated cells, suggesting the onset of ER stress. Because ER and mitochondria work closely to maintain cellular homeostasis, we next asked whether mitochondrial health was affected during LT. However, our measurement of reactive oxygen species (ROS) using the DCF assay revealed no significant differences between control and PA-treated groups, suggesting that mitochondrial oxidative stress was not prominent under these conditions. Overall, these findings indicate that lipotoxic stress primarily disrupts ER homeostasis and insulin maturation in β cells, potentially representing an early adaptive response to FFA-induced stress before overt mitochondrial or protein-folding defects occur.
