Mechanisms and neuroanatomical bases of metabolic depression in the Djungarian hamster.

• Applicant: Professorin Dr. Annika Herwig
• Subject Area: Animal Physiology and Biochemistry
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 399844041

Daily torpor is a powerful strategy of Djungarian hamsters to reduce energy expenditure in response to predictable or acute energetic challenges. During torpor, metabolic rate is suppressed by 75% and body temperature drops to ≥ 15°C. Although torpor physiology is well studied in this species, knowledge about regulatory systems and mechanisms is still fragmented. The use of torpor is, directly or indirectly, related to energy shortage, and previous studies have suggested that glucose availability may be involved in its regulation. However, data have remained controversial. Here we want to assess the role of glucose availability in different forms of torpor – spontaneous torpor that occurs in a seasonal context as well as fasting induced torpor that can be used in response to acute food restriction. By using a novel telemetry method, we want to continuously measure serum glucose levels in vivo during torpor episodes, precisely relay it to measurements of metabolic rate and body temperature and thereby identify its role in torpor induction. Analysis of glucose sensing in tanycytes at the blood-brain interface and detailed gene expression studies in the hypothalamus will add important information about transmission to the brain and potential regulatory mechanisms. In a second approach, we aim to gain precise anatomical information about hypothalamic centers involved in torpor induction. Currently, information about active brain centers in torpor is very scarce, although this information is essential to understand the basis of metabolic depression. Here we want to combine anatomical and functional investigations, by using detailed immunohistochemical c-Fos analysis coupled with Illumina sequencing of specifically identified hypothalamic nuclei activated during torpor entrance. Combining state of the art in vivo, neurophysiological, anatomical and molecular methods, this project aims to better understand the mechanisms of metabolic depression in mammals. Disentangling the regulatory mechanisms of torpid states, bears great potential for clinical applications that could greatly benefit from controlling metabolism in humans.

• DFG Programme: Research Grants