Z 2 - Verwaltungsprojekt
Endocrinology, Diabetology, Metabolism
Final Report Abstract
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.
Publications
- 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
(See online at https://doi.org/10.1152/ajpendo.00020.2010) - 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
(See online at https://doi.org/10.1016/j.metabol.2010.02.016) - 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
(See online at https://doi.org/10.1016/j.neuroimage.2013.07.028) - 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
(See online at https://doi.org/10.1016/j.neuroimage.2014.12.073) - 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
(See online at https://doi.org/10.1016/j.metabol.2016.03.013) - 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
(See online at https://doi.org/10.1056/NEJMoa1512693) - 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
(See online at https://doi.org/10.1210/jc.2016-1788) - 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
(See online at https://doi.org/10.1016/j.metabol.2018.01.003) - 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
(See online at https://doi.org/10.1038/s41591-018-0015-9) - 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
(See online at https://doi.org/10.2337/db18-0440)
