Research Focus

Research Focus

Energy homeostasis is a major determinant of health- and life span. While caloric excess leads to insulin resistance, cardio metabolic disease and premature death, caloric restriction prevents and cures these traits. Our group investigates novel regulators of energy, glucose and lipid homeostasis and their impact on insulin resistance, type 2 diabetes, obesity and aging.

Role of INDY and other SLC Transporters in Metabolic Disease

Reduced expression of the Indy (= I’m Not Dead Yet) gene, which encodes a cell surface transporter for tri- and dicarboxylic acids, prolongs life and health span in a manner akin to caloric restriction in D. melanogaster and C. elegans. In order to test if Indy also effects mammalian metabolism, we generated the Indy knock out mouse. Similar to D. melanogaster, mINDY knockout mice mimic a state of caloric restriction with increased mitochondrial biogenesis, hepatic lipid oxidation, and insulin sensitivity. In addition, mINDY knockout mice are protected from adiposity and insulin resistance that evolves with high-fat feeding and aging.

In our group, we address the question if deletion of the mammalian Indy gene (mIndy) also promotes longevity in mammals and we look for molecular mechanisms explaining the effects of mIndy in metabolism, aging, and life span. We will establish the influence of mIndy in distinct metabolically active tissues in vivo and pinpoint transcriptional regulators of mIndy. In a translational approach, the effect of mIndy on human metabolism and the influence of mINDY’s substrates on mammalian metabolism will be determined.

It is our aim to identify new physiological concepts connecting metabolic regulation to aging and longevity and to implement these findings into innovative pharmacological approaches to treat obesity, insulin resistance, and senescence.