pereira.lab.uiowa.edu

Research

Our lab studies the role of mitochondrial dynamics and stress response pathways in cardiometabolic health. The prevalence of obesity and associated comorbidities, such as diabetes and cardiovascular disease, have increased dramatically over the last several decades. Activation of thermogenic adipocytes has emerged as a therapeutic strategy to increase energy expenditure and counteract weight gain. Recent evidence in mice and humans suggest a role for brown adipose tissue (BAT) in regulating the secretion of endocrine factors or batokines, such as fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), that may promote cardiometabolic health by regulating energy homeostasis, glucose metabolism and cardiovascular function.

Our recent work in mice lacking the mitochondrial fusion protein optic atrophy 1 (OPA1) in BAT and in skeletal muscle demonstrated that mitochondrial stress induces the integrated stress response (ISR), which is required to improve metabolic fitness, partially via FGF21 secretion as a batokine. We also demonstrated that the ISR is induced in BAT in response to physiological stress, such as cold stress. Our research program aims to understand the role of mitochondrial dynamics and the ISR in the regulation of systemic metabolic adaptations in response to cold, diet-induced obesity, cardiac stress and mitochondrial dysfunction.

Our primary research projects focus on: 1. Investigating the role of PKR-like ER kinase (PERK) as an upstream regulator of ISR activation in BAT; 2. The role of the activating transcription factor 4 (ATF4), the main effector of the ISR, in BAT thermogenesis and metabolic homeostasis. 3. The role of GDF15 in the regulation of BAT-mediated metabolic protection. Additional projects in the lab are focused on investigating the role of mitochondrial dynamics and ATF4 in skeletal muscle in the pathophysiology of obesity and insulin resistance. We believe these studies have the potential of identifying new pathways that can be targeted to counteract obesity and its comorbidities.