Helmholtz Diabetes Center Institute for Diabetes and Obesity
The Institute for Diabetes and Obesity (IDO) investigates the diseases of metabolic syndrome by means of systems biological and translational approaches on the basis of cellular systems, genetically modified mouse models and clinical intervention studies.
The Institute for Diabetes and Obesity (IDO) investigates the diseases of metabolic syndrome by means of systems biological and translational approaches on the basis of cellular systems, genetically modified mouse models and clinical intervention studies.
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Recent Publication Highlights
See allApril 2025 Nature Metabolism
Agonists and antagonists of the glucose-dependent insulinotropic polypeptide receptor (GIPR) enhance body weight loss induced by glucagon-like peptide-1 receptor (GLP-1R) agonism. However, while GIPR agonism decreases body weight and food intake in a GLP-1R-independent manner via GABAergic GIPR+ neurons, it remains unclear whether GIPR antagonism affects energy metabolism via a similar mechanism. Here we show that the body weight and food intake effects of GIPR antagonism are eliminated in mice with global loss of either Gipr or Glp-1r but are preserved in mice with loss of Gipr in either GABAergic neurons of the central nervous system or peripherin-expressing neurons of the peripheral nervous system. Single-nucleus RNA-sequencing shows opposing effects of GIPR agonism and antagonism in the dorsal vagal complex, with antagonism, but not agonism, closely resembling GLP-1R signalling. Additionally, GIPR antagonism and GLP-1R agonism both regulate genes implicated in synaptic plasticity. Collectively, we show that GIPR agonism and antagonism decrease body weight via different mechanisms, with GIPR antagonism, unlike agonism, depending on functional GLP-1R signalling.
January 2025 Cell Press
Neuroendocrine gut–brain signaling in obesity
The past decades have witnessed the rise and fall of several, largely unsuccessful, therapeutic attempts to bring the escalating obesity pandemic to a halt. Looking back to look ahead, the field has now put its highest hopes in translating insights from how the gastrointestinal (GI) tract communicates with the brain to calibrate behavior, physiology, and metabolism. A major focus of this review is to summarize the latest advances in comprehending the neuroendocrine aspects of this so-called ‘gut–brain axis’ and to explore novel concepts, cutting-edge technologies, and recent paradigm-shifting experiments. These exciting insights continue to refine our understanding of gut–brain crosstalk and are poised to promote the development of additional therapeutic avenues at the dawn of a new era of antiobesity therapeutics.
December 2024 Nature Reviews Endocrinology
Advances in appetite regulation by the arcuate nucleus
In 2024, new insights identified a cluster of leptin-targeted neurons and integrative networks that link sensory inputs (heat and food perception) with feeding centres and peripheral systems. Key findings revealed hypothalamic site-specific adaptive mechanisms, in which nutritional state-dependent remodelling of extracellular compounds and neuropeptide transmission calibrate appetite via the arcuate nucleus.
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