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The catch-up fat phenomenon is an evolutionary conserved physiological response to a starvationrefeeding cycle. It is characterized by long-term suppression of thermogenesis, reduced body protein regain and an increase in fat mass above basal level during refeeding. Clinically, it characterises weight cycling in overweight patients which is associated with increasing fat mass (visceral fat) and increased morbidity (e.g. insulin resistance, inflammation). In this project, the physiological, cellular and molecular mechanisms of this phenomenon will be investigated in humans, mice and C. elegans. It is hypothesized that refeeding a low GI (=glycemic index)- diet after weight loss prevents the catchup fat phenomenon and its sequelae. This translational research will provide comprehensive insights into the catch-up fat phenomenon as well as provide a suitable strategy of its prevention.
In a human intervention study, changes in physiological, metabolic, and neuroendocrine functions in response to weight cycling will be investigated under controlled conditions in normal weight subjects. The mechanisms of the catch-up fat phenomenon are analysed starting from stable energy balance followed by overfeeding, weight loss and weight regain following weight loss (refeeding). Changes in body composition (including ectopic fat), metabolism (resting energy expenditure, substrate oxidation rates, insulin resistance) and plasma hormone concentrations will be assessed. Fat tissue probes will be used to characterise key enzymes and signalling pathways, redox status and whole genome expression. Modulation of the hormonal response to weight cycling is brought about by varying macronutrient content and glycemic index of the diets. We hypothesize that, insulin and leptin resistance are explained by increased insulin secretion during the refeeding period. Both, adaptive thermogenesis as well as insulin and leptin resistance can be ameliorated by attenuation of the increase in insulin and leptin secretion during refeeding a low GI diet after weight loss.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| low GI, low GI | Experimental | low GI diet (semi starvation phase) followed by low GI diet in the refeeding phase |
|
| low GI, high GI | Experimental | low GI diet (semi starvation phase) followed by high GI diet in the refeeding phase |
|
| high GI, low GI | Experimental | high GI diet (semi starvation phase) followed by low GI diet in the refeeding phase |
|
| high GI, high GI | Experimental | high GI diet (semi starvation phase) followed by high GI diet in the refeeding phase |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dietary intervention by varying GI diets | Other | The human study intends to characterise the partitioning of weight gain during refeeding and to affect the catch-up fat phenomenon by the glycemic index (GI) of the diet. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in body composition and energy metabolism after 3 weeks of underfeeding and 2 following weeks of refeeding | Body composition measurement including BODPOD, QMR, BIA Energy Metabolism measurement using indirect calorimetry | Body composition measurement after 4 and 6 study weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Manfred J. Müller, Prof. | Institute of Human Nutrition, University of Kiel | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Human Nutrition | Kiel | Schleswig-Holstein | 24105 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28060600 | Derived | Breusing N, Lagerpusch M, Engstler AJ, Bergheim I, Mueller MJ, Bosy-Westphal A. Influence of Energy Balance and Glycemic Index on Metabolic Endotoxemia in Healthy Men. J Am Coll Nutr. 2017 Jan;36(1):72-79. doi: 10.1080/07315724.2016.1156036. Epub 2017 Jan 6. | |
| 26590912 | Derived | Geisler C, Braun W, Pourhassan M, Schweitzer L, Gluer CC, Bosy-Westphal A, Muller MJ. Gender-Specific Associations in Age-Related Changes in Resting Energy Expenditure (REE) and MRI Measured Body Composition in Healthy Caucasians. J Gerontol A Biol Sci Med Sci. 2016 Jul;71(7):941-6. doi: 10.1093/gerona/glv211. Epub 2015 Nov 20. |
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| 26399868 | Derived | Muller MJ, Enderle J, Pourhassan M, Braun W, Eggeling B, Lagerpusch M, Gluer CC, Kehayias JJ, Kiosz D, Bosy-Westphal A. Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota Starvation Experiment revisited. Am J Clin Nutr. 2015 Oct;102(4):807-19. doi: 10.3945/ajcn.115.109173. Epub 2015 Sep 23. |
| 26016860 | Derived | Schweitzer L, Geisler C, Pourhassan M, Braun W, Gluer CC, Bosy-Westphal A, Muller MJ. What is the best reference site for a single MRI slice to assess whole-body skeletal muscle and adipose tissue volumes in healthy adults? Am J Clin Nutr. 2015 Jul;102(1):58-65. doi: 10.3945/ajcn.115.111203. Epub 2015 May 27. |
| 25723719 | Derived | Karschin J, Lagerpusch M, Enderle J, Eggeling B, Muller MJ, Bosy-Westphal A. Endocrine determinants of changes in insulin sensitivity and insulin secretion during a weight cycle in healthy men. PLoS One. 2015 Feb 27;10(2):e0117865. doi: 10.1371/journal.pone.0117865. eCollection 2015. |
| 23946346 | Derived | Lagerpusch M, Enderle J, Eggeling B, Braun W, Johannsen M, Pape D, Muller MJ, Bosy-Westphal A. Carbohydrate quality and quantity affect glucose and lipid metabolism during weight regain in healthy men. J Nutr. 2013 Oct;143(10):1593-601. doi: 10.3945/jn.113.179390. Epub 2013 Aug 14. |