2. Behavioral Biology TALKS - Deutsche Zoologische Gesellschaft

cloned into a RNA producing vector for expression in Xenopus-oocytes. Transport
studies with selected substances will be carried out to characterize their substrate
spectrum. Feeding experiments of L. jacobaeae with several potentially harmful
substances revealed so far, that these substances were transferred into the
hemolymph without causing damage to the organisms.
Invited speaker 2: Chair – Ulrich Hoeger A 704 / 11:00
Alexander Tups (Marburg)
The interplay of leptin, insulin and nutrients in the hypothalamus: A key to
understand the pathophysiology of type II diabetes?
Author: Alexander Tups 1
Affiliation: 1 Department of Animal Physiology, Faculty of Biology, Philipps University
Marburg
More than ten years ago it was discovered that the brain plays a pivotal role in the
regulation of whole body glucose homeostasis. The adiposity signals leptin and
insulin mediate glucose homeostasis through hypothalamic signal transduction
mechanisms. We and others could show that not the body fat per se contributes to
the pathogenesis of type II diabetes, rather leptin resistance, typically associated with
obesity, appears to be one leading cause of this disease. Employing physiological
animal models of leptin resistance such as the Djungarian hamster (Phodopus
sungorus) or mice fed a high fat diet together with state of the art viral gene therapy,
we identified that the WNT/β-catenin pathway, typically involved in tumorigenesis
and embryogenesis, acts as a key regulator of glucose homeostasis via integrating the
leptin and insulin signal in the hypothalamus. Hypothalamic inhibition of this pathway
led to severe glucose intolerance and obesity in mice fed a high fat diet (HFD). Using
leptin-deficient mice, we demonstrated that not hyper-leptinemia leads to diabetes,
rather diet-induced hypothalamic inflammation disrupts the physiological feed-back
to the leptin and insulin signal in the brain. Leptin deficient mice fed a high fat diet
surprisingly developed central leptin resistance that was associated with extreme
glucose intolerance. Pharmacological inhibition of hypothalamic inflammation
reversed leptin resistance and improved glucose tolerance in these mice. Certain
dietary flavonoids act as natural inhibitors of the hypothalamic inflammation
pathway. Dietary intervention approaches and gene therapy might be an important
tool to further understand and combat the patho-physiology of obesity and diabetes.
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