Z 2 - Verwaltungsprojekt

• Antragstellerin: Professorin Dr. Annette Grüters-Kieslich
• Fachliche Zuordnung: Kinder- und Jugendmedizin ; Endokrinologie, Diabetologie, Metabolismus
• Förderung: Förderung von 2009 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 101434729

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

In summary, our data demonstrated the efficacy of a multimodal weight maintenance regime as long as such an intervention is performed but did not result in a sustained body weight reduction. This finding challenges the therapeutic concept of sustained weight management programs, as even programs as long as 15 months (three months weight reduction + 12 months weight maintenance) have no persistent effects which urges the need for novel treatment approaches such as recently shown by our group in monogenic obesity. Despite the preventive effect on weight regain during the intervention period, no effect on circulating hormonal parameters associated with body weight was observed. Although weight loss resulted in a substantial perturbation of several hormonal circuits involved in regulation of energy balance, no persisting adaption of neuro-endocrine parameters was found. These results challenges the hypothesis that a long persisting counter-regulation of circulating neuro-endocrine factors occurs after weight loss and mediates body weight regain, which was suggested in previous studies. Clearly, our analysis is restricted to circulating hormones and does not exclude the possibility that modifications at receptor level or intracellular signaling contribute to the phenomenon of body weight regain. The lack of specific hormones may occur at tissue level only and measurement at circulation may be misleading. The finding of a successful endocrine effect on weight loss of a MSH-analog in patients with rare severe early obesity, imply that, once local-hypothalamic- defects also in common severe obesity might be detectable, an endocrine treatment by peripheral application of a missing neuropeptide might be a realistic therapeutic option.

Projektbezogene Publikationen (Auswahl)

• Physiological modulation of circulating FGF21: relevance of free fatty acids and insulin. AmJPhysiol EndocrinolMetab. 2010;299:E126-E130
  Mai K, Bobbert T, Groth C, Assmann A, Meinus S, Kraatz J, Andres J, Arafat AM, Pfeiffer AF, Mohlig M and Spranger J
  
• Relation between fibroblast growth factor-21, adiposity, metabolism, and weight reduction. Metabolism. 2010
  Mai K, Schwarz F, Bobbert T, Andres J, Assmann A, Pfeiffer AF and Spranger J
  
• The role of neural impulse control mechanisms for dietary success in obesity. NeuroImage. 2013;83:669-78
  Weygandt M, Mai K, Dommes E, Leupelt V, Hackmack K, Kahnt T, Rothemund Y, Spranger J and Haynes JD
  
• Impulse control in the dorsolateral prefrontal cortex counteracts post-diet weight regain in obesity. NeuroImage. 2015;109:318-27
  Weygandt M, Mai K, Dommes E, Ritter K, Leupelt V, Spranger J and Haynes JD
  
• ANP system activity predicts variability of fat mass reduction and insulin sensitivity during weight loss. Metabolism. 2016;65:935-43
  Brachs M, Wiegand S, Leupelt V, Ernert A, Kintscher U, Jumpertz von Schwarzenberg R, Decker AM, Bobbert T, Hubner N, Chen W, Krude H, Spranger J and Mai K
  
• Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist. N Engl J Med. 2016;375:240-6
  Kuhnen P, Clement K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, Mai K, Blume-Peytavi U, Gruters A and Krude H
  
• Weight Loss Partially Restores Glucose-Driven Betatrophin Response in Humans. J Clin Endocrinol Metab. 2016;101:4014-4020
  Maurer L, Brachs S, Decker AM, Brachs M, Leupelt V, Jumpertz von Schwartzenberg R, Ernert A, Bobbert T, Krude H, Spranger J and Mai K
  
• Effects of a combined dietary, exercise and behavioral intervention and sympathetic system on body weight maintenance after intended weight loss: Results of a randomized controlled trial. Metabolism. 2018;83:60-67
  Mai K, Brachs M, Leupelt V, Jumpertz-von Schwartzenberg R, Maurer L, Gruters- Kieslich A, Ernert A, Bobbert T, Krude H and Spranger J
  
• MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency. Nat Med. 2018;24:551-555
  Clement K, Biebermann H, Farooqi IS, Van der Ploeg L, Wolters B, Poitou C, Puder L, Fiedorek F, Gottesdiener K, Kleinau G, Heyder N, Scheerer P, Blume-Peytavi U, Jahnke I, Sharma S, Mokrosinski J, Wiegand S, Muller A, Weiss K, Mai K, Spranger J, Gruters A, Blankenstein O, Krude H and Kuhnen P
  
• An Integrated Understanding of the Molecular Mechanisms of How Adipose Tissue Metabolism Affects Long-term Body Weight Maintenance. Diabetes. 2019 Jan;68(1):57-65
  Mai K, Li L, Wiegand S, Brachs M, Leupelt V, Ernert A, Kühnen P, Hübner N, Robinson P, Chen W, Krude H, Spranger J