Affiliations 1 German Diabetes Foundation, Munich, Germany 2 Division of Endocrinology and Diabetology, University Obesity Centre Hamburg, University Hospital HamburgEppendorf, Germany 3 German Centre for Diabetes Research (DZD e. V.), Neuherberg, Germany 4 Department of Internal Medicine IV, Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Germany 5 Department of Internal Medicine I, Marienhospital, Stuttgart, Germany 6 Department of Internal Medicine I, University Hospital Bergmannsheil, Bochum, Germany 7 Department of Internal Medicine I, University Hospital RWTH, Aachen, Germany 8 Diabetes Centre Bochum-Hattingen, St.-Josef-Hospital, Ruhr-University, Bochum, Germany 9 MVZ Metabolic Medicine Leipzig, Leipzig, Germany 10 Department of Internal Medicine – Gastroenterology, Diabetology/Endocrinology and Nutritional Medicine, St. Josefkrankenhaus Heidelberg GmbH, Heidelberg, Germany Bibliography Exp Clin Endocrinol Diabetes DOI 10.1055/a-1624-3449 ISSN 0947-7349 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany
The hypothalamus in the central nervous system (CNS) has important functions in controlling systemic metabolism. A calorie-rich diet triggers CNS immune activation, impairing metabolic control and promoting obesity and Type 2 Diabetes (T2D), but the mechanisms driving hypothalamic immune activation remain unclear. Here we identify regulatory T cells (Tregs) as key modulators of hypothalamic immune responses. In mice, calorie-rich environments activate hypothalamic CD4+ T cells, infiltrating macrophages and microglia while reducing hypothalamic Tregs. mRNA profiling of hypothalamic CD4+ T cells reveals a Th1-like activation state, with increased Tbx21, Cxcr3 and Cd226 but decreased Ccr7 and S1pr1. Importantly, results from Treg loss-of function and gain-of-function experiments show that Tregs limit hypothalamic immune activation and reverse metabolic impairments induced by hyper-caloric feeding. Our findings thus help refine the current model of Treg-centered immune-metabolic crosstalk in the brain and may contribute to the development of precision immune modulation for obesity and diabetes.
The autonomic nervous system is a crucial mediator between the central nervous system and peripheral tissues and is essential for maintaining homeostasis. In this Review, we discuss the bidirectional communication between the autonomic nervous system and metabolic tissues in humans, focusing on the coordination of systemic glucose and lipid metabolism through autonomic signalling across changing physiological states. We also discuss the crosstalk between autonomic and immune pathways and its relevance for metabolic control. An overview of current methodologies to assess autonomic function in humans shows that quantifying organ-specific autonomic outflows remains challenging. Chronic disturbances in autonomic regulation are increasingly recognized as contributors to metabolic diseases such as obesity and type 2 diabetes mellitus. Hence, emerging therapeutic strategies targeting autonomic function could offer promising opportunities to improve metabolic health. Progress will depend on the development of tools to selectively assess autonomic input to individual metabolic organs. Addressing high inter-individual variability and capturing the temporal dynamics of organ-specific autonomic regulation will be essential for advancing mechanistic insights, ultimately enabling clinical translation. Chronic disturbances in autonomic regulation are increasingly recognized as contributors to metabolic diseases such as obesity and type 2 diabetes mellitus. In this Review, Wangler and colleagues discuss bidirectional communication between the autonomic nervous system and peripheral tissues in the coordination of glucose and lipid metabolism as well as emerging therapies targeting autonomic pathways that could improve metabolic health.
The menstrual cycle impacts food intake, peripheral metabolism, and brain function. One well-known central regulator of eating behavior is the hormone insulin. Here, we show that the responsiveness of functional brain networks to central insulin varies dynamically across the menstrual cycle in premenopausal women. Intranasal insulin (INI) administration increases functional connectivity within networks that support decision-making processes (namely the default mode and salience network) in the follicular compared to the luteal phase of the menstrual cycle. In contrast, INI decreases functional connectivity within the somatosensory network during the follicular phase relative to the luteal phase. In response to visual food cues, hippocampus and dorsal striatum activity are higher in the luteal compared to the follicular phase, particularly to sweet food. Estradiol and progesterone levels predict these changes. This could contribute to higher food craving and food intake observed in the luteal phase. Our findings emphasize sex hormones' role in modulating brain sensitivity to hormonal signals and external stimuli.
Agentic AI systems are deployed with expectations of substantial productivity gains, yet rigorous empirical evidence reveals systematic discrepancies between pre-deployment expectations and post-deployment outcomes. We review controlled trials and independent validations across software engineering, clinical documentation, and clinical decision support to quantify this expectation-realisation gap. In software development, experienced developers expected a 24
