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Manfred Hallschmid (academic)

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Manfred Hallschmid (he/him), PhD, is Professor (W3) of Behavioral Neurobiology at the Department of Medical Psychology and Behavioral Neurobiology of the University of Tübingen, Germany. He obtained his PhD in psychology/human biology in 2005 and received awards by the German Society of Psychology, the German Society of Endocrinology, and the German Diabetes Society. Manfred Hallschmid’s primary research area is the central nervous regulation of energy fluxes in humans, with a focus on the role of neuropeptidergic messengers for metabolic control, as well as on the relationship between sleep, food intake and cognition. Hallschmid’s studies have provided insights into how metabolic processes, hormones, and sleep interact to modulate both physical and cognitive health. His work has broad clinical implications for conditions such as diabetes, obesity and neurodegenerative disorders.

Research Interests

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Manfred Hallschmid’s work includes studies on the role of oxytocin in food intake control, on brain effects of insulin, on the role of sleep for metabolic regulation, and on cognitive control as a target of neuromodulation-based interventions to improve eating behavior. His studies were among the first to provide evidence for a critical role of sex differences in central nervous insulin effects in humans, and to show that oxytocin, a hormone predominantly known for its psychosocial effects, regulates eating behavior in humans. Manfred Hallschmid’s research ranges from experiments in healthy humans to clinical populations to animal models and highlights the crucial links between metabolism and brain health.

His group showed that after intranasal administration, oxytocin markedly curbs primarily reward-driven (hedonic) calorie intake: in comparison to placebo, oxytocin reduced the consumption of chocolate cookies by 25%[1]. Remarkably, the potential of acutely administered oxytocin to reduce food intake appears to be even more pronounced in males with increased body weight[2]. In related experiments[3], oxytocin’s acute contribution to glucose homeostasis was studied in healthy, fasted male individuals. Intranasal oxytocin attenuated the peak excursion of plasma glucose and augmented the early increases in insulin and C-peptide concentrations in response to an oral glucose tolerance test while slightly blunting insulin and C-peptide peaks. Oral minimal model analyses revealed that oxytocin, compared with placebo, induced a pronounced increase in β-cell responsivity. These results highlight the role of oxytocin in the acute regulation of glucose metabolism in humans. While the conclusion that the oxytocin system may be a target of antidiabetic treatment, results obtained in individuals with obesity[4] or type 2 diabetes[5] indicate that oxytocin administration is less effective in individuals with chronically impaired insulin sensitivity.

Manfred Hallschmid’s studies on the brain impact of insulin revealed that the hormone, when administered via the intranasal route[6], reduces food intake[7] and, across longer intervention periods, body weight[8] in healthy, normal-weight male individuals. These findings were among the first to confirm in humans the concept that insulin, like leptin, provides the brain with negative feedback on energy stored as body fat and thereby contributes to the regulation of food intake. In a parallel line of work, Hallschmid, together with Christian Benedict, investigated the potential of intranasal insulin to improve memory function in humans[9], a topic of particular interest in the context of memory impairments like Alzheimer’s disease[10]. Notably, Hallschmid’s findings suggest that the role of brain insulin in food intake control may be more relevant in males than females, underlining the role of sex differences for brain functions and metabolic control. In further experiments, Hallschmid and coworkers investigated brain insulin sensitivity in postmenopausal females[11] and the interplay between estrogen and insulin in food intake control[12] and memory function[13]. These studies open up avenues for future research into sex-specific differences in hormonal influences on cognition. With colleagues at the University of Tübingen, Hallschmid is currently exploring the nuanced complexities of sex and gender differences in brain function[14].

While Manfred Hallschmid’s research also tackles topics like hedonic hunger in obesity[15] and how to normalize hunger in individuals with increased body weight with the help of fMRI neurofeedback[16], his studies have moreover added significant insights into the role of sleep for the control of eating behavior and peripheral metabolism[17][18]. Work by Hallschmid and colleagues has, for example, shown that sleep contributes to the formation of metabolic memory because sleep deprivation prevents the adaptation of the counterregulatory response to recurrent hypoglycemia[19]. Together with Jan Born, he demonstrated that slow-wave sleep, which predominantly occurs during the first night-half, renormalizes the strength of synaptic connections in the hypothalamus and, thereby, likely supports homeostatic control processes[20]. On the other hand, pilot experiments indicate that – in healthy men – intensifying sleep slow oscillations does not acutely improve metabolic control[21]. With a view to women’s mental health across the reproductive years, Hallschmid’s group came up with good news for expecting women by showing that, despite popular beliefs about the “baby brain”, sleep-associated memory formation is not impaired during the third trimester of pregnancy[22].

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References

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  1. ^ Ott, Volker; Finlayson, Graham; Lehnert, Hendrik; Heitmann, Birte; Heinrichs, Markus; Born, Jan; Hallschmid, Manfred (2013-10-01). "Oxytocin Reduces Reward-Driven Food Intake in Humans". Diabetes. 62 (10): 3418–3425. doi:10.2337/db13-0663. ISSN 0012-1797. PMC 3781467. PMID 23835346.{{cite journal}}: CS1 maint: PMC format (link)
  2. ^ Thienel, M; Fritsche, A; Heinrichs, M; Peter, A; Ewers, M; Lehnert, H; Born, J; Hallschmid, M (2016-11). "Oxytocin's inhibitory effect on food intake is stronger in obese than normal-weight men". International Journal of Obesity. 40 (11): 1707–1714. doi:10.1038/ijo.2016.149. ISSN 0307-0565. PMC 5116063. PMID 27553712. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  3. ^ Klement, Johanna; Ott, Volker; Rapp, Kristina; Brede, Swantje; Piccinini, Francesca; Cobelli, Claudio; Lehnert, Hendrik; Hallschmid, Manfred (2017-02-01). "Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men". Diabetes. 66 (2): 264–271. doi:10.2337/db16-0569. ISSN 0012-1797.
  4. ^ Brede, Swantje; Fehr, Sebastian; Dalla‐Man, Chiara; Cobelli, Claudio; Lehnert, Hendrik; Hallschmid, Manfred; Klement, Johanna (2019-02). "Intranasal oxytocin fails to acutely improve glucose metabolism in obese men". Diabetes, Obesity and Metabolism. 21 (2): 424–428. doi:10.1111/dom.13527. ISSN 1462-8902. {{cite journal}}: Check date values in: |date= (help)
  5. ^ Goll, Nina; Moszka, Nina; Kantartzis, Konstantinos; Preissl, Hubert; Gruber, Tim; Fritsche, Louise; Jumpertz‐von Schwarzenberg, Reiner; García‐Cáceres, Cristina; Fritsche, Andreas; Hallschmid, Manfred (2024-10). "Oxytocin does not acutely improve glucose tolerance in men with type 2 diabetes". Diabetes, Obesity and Metabolism. 26 (10): 4562–4570. doi:10.1111/dom.15812. ISSN 1462-8902. {{cite journal}}: Check date values in: |date= (help)
  6. ^ Hallschmid, Manfred (2021-04). "Intranasal insulin". Journal of Neuroendocrinology. 33 (4). doi:10.1111/jne.12934. ISSN 0953-8194. {{cite journal}}: Check date values in: |date= (help)
  7. ^ Benedict, Christian; Kern, Werner; Schultes, Bernd; Born, Jan; Hallschmid, Manfred (2008-04). "Differential Sensitivity of Men and Women to Anorexigenic and Memory-Improving Effects of Intranasal Insulin". The Journal of Clinical Endocrinology & Metabolism. 93 (4): 1339–1344. doi:10.1210/jc.2007-2606. ISSN 0021-972X. {{cite journal}}: Check date values in: |date= (help)
  8. ^ Hallschmid, Manfred; Benedict, Christian; Schultes, Bernd; Fehm, Horst-Lorenz; Born, Jan; Kern, Werner (2004-11-01). "Intranasal Insulin Reduces Body Fat in Men but not in Women". Diabetes. 53 (11): 3024–3029. doi:10.2337/diabetes.53.11.3024. ISSN 0012-1797.
  9. ^ Benedict, C (2004-11). "Intranasal insulin improves memory in humans". Psychoneuroendocrinology. 29 (10): 1326–1334. doi:10.1016/j.psyneuen.2004.04.003. {{cite journal}}: Check date values in: |date= (help)
  10. ^ Hallschmid, Manfred (2021-01). "Intranasal Insulin for Alzheimer's Disease". CNS Drugs. 35 (1): 21–37. doi:10.1007/s40263-020-00781-x. ISSN 1172-7047. PMC 7873098. PMID 33515428. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  11. ^ Krug, Rosemarie; Benedict, Christian; Born, Jan; Hallschmid, Manfred (2010-12-01). "Comparable Sensitivity of Postmenopausal and Young Women to the Effects of Intranasal Insulin on Food Intake and Working Memory". The Journal of Clinical Endocrinology & Metabolism. 95 (12): E468–E472. doi:10.1210/jc.2010-0744. ISSN 0021-972X.
  12. ^ Krug, Rosemarie; Mohwinkel, Linda; Drotleff, Bernhard; Born, Jan; Hallschmid, Manfred (2018-04-01). "Insulin and Estrogen Independently and Differentially Reduce Macronutrient Intake in Healthy Men". The Journal of Clinical Endocrinology & Metabolism. 103 (4): 1393–1401. doi:10.1210/jc.2017-01835. ISSN 0021-972X.
  13. ^ Krug, Rosemarie; Beier, Laura; Lämmerhofer, Michael; Hallschmid, Manfred (2022-01-18). "Distinct and Convergent Beneficial Effects of Estrogen and Insulin on Cognitive Function in Healthy Young Men". The Journal of Clinical Endocrinology & Metabolism. 107 (2): e582–e593. doi:10.1210/clinem/dgab689. ISSN 0021-972X. PMC 8764344. PMID 34534317.{{cite journal}}: CS1 maint: PMC format (link)
  14. ^ Derntl, Birgit; Hage, Steffen R.; Hallschmid, Manfred (2024-03). "Making Sense of Sex in Neuroscience". Biological Psychiatry Global Open Science. 4 (2): 100292. doi:10.1016/j.bpsgos.2024.100292. PMC 10945429. PMID 38501116. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  15. ^ Schultes, Bernd; Ernst, Barbara; Wilms, Britta; Thurnheer, Martin; Hallschmid, Manfred (2010-08). "Hedonic hunger is increased in severely obese patients and is reduced after gastric bypass surgery". The American Journal of Clinical Nutrition. 92 (2): 277–283. doi:10.3945/ajcn.2009.29007. {{cite journal}}: Check date values in: |date= (help)
  16. ^ Kohl, Simon H.; Veit, Ralf; Spetter, Maartje S.; Günther, Astrid; Rina, Andriani; Lührs, Michael; Birbaumer, Niels; Preissl, Hubert; Hallschmid, Manfred (2019-05). "Real-time fMRI neurofeedback training to improve eating behavior by self-regulation of the dorsolateral prefrontal cortex: A randomized controlled trial in overweight and obese subjects". NeuroImage. 191: 596–609. doi:10.1016/j.neuroimage.2019.02.033. {{cite journal}}: Check date values in: |date= (help)
  17. ^ Benedict, Christian; Kern, Werner; Schmid, Sebastian M.; Schultes, Bernd; Born, Jan; Hallschmid, Manfred (2009-04). "Early morning rise in hypothalamic–pituitary–adrenal activity: A role for maintaining the brain's energy balance". Psychoneuroendocrinology. 34 (3): 455–462. doi:10.1016/j.psyneuen.2008.10.010. {{cite journal}}: Check date values in: |date= (help)
  18. ^ Schmid, Sebastian M; Hallschmid, Manfred; Schultes, Bernd (2015-01). "The metabolic burden of sleep loss". The Lancet Diabetes & Endocrinology. 3 (1): 52–62. doi:10.1016/S2213-8587(14)70012-9. {{cite journal}}: Check date values in: |date= (help)
  19. ^ Meyhöfer, Svenja; Dembinski, Katharina; Schultes, Bernd; Born, Jan; Wilms, Britta; Lehnert, Hendrik; Hallschmid, Manfred; Meyhöfer, Sebastian M. (2022-07). "Sleep deprivation prevents counterregulatory adaptation to recurrent hypoglycaemia". Diabetologia. 65 (7): 1212–1221. doi:10.1007/s00125-022-05702-9. ISSN 0012-186X. PMC 9174142. PMID 35445819. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  20. ^ Liu, Jianfeng; Niethard, Niels; Lun, Yu; Dimitrov, Stoyan; Ehrlich, Ingrid; Born, Jan; Hallschmid, Manfred (2024-08-20). Yang, Guang (ed.). "Slow-wave sleep drives sleep-dependent renormalization of synaptic AMPA receptor levels in the hypothalamus". PLOS Biology. 22 (8): e3002768. doi:10.1371/journal.pbio.3002768. ISSN 1545-7885. PMC 11364421. PMID 39163472.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  21. ^ Santiago, João C.P.; Ngo, Hong-Viet; Jickeli, Carola; Peter, Andreas; Hallschmid, Manfred (2019-01). "Intensifying sleep slow oscillations does not improve metabolic control in healthy men". Psychoneuroendocrinology. 99: 1–7. doi:10.1016/j.psyneuen.2018.08.028. {{cite journal}}: Check date values in: |date= (help)
  22. ^ Zinke, Katharina; Lehnert, Vanessa; Fritsche, Andreas; Preissl, Hubert; Hallschmid, Manfred (2021-06). "Pregnant women do not display impaired memory formation across one night of sleep". Journal of Sleep Research. 30 (3). doi:10.1111/jsr.13204. ISSN 0962-1105. {{cite journal}}: Check date values in: |date= (help)
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