RSS-Feed abonnieren
PDF herunterladen
DOI: 10.1055/a-0801-9704
Frühe Fettgewebsdysfunktion bei Kindern mit Adipositas
Early adipose tissue dysfunction in children with obesityPublikationsverlauf
Publikationsdatum:
22. Februar 2019 (online)
Zusammenfassung
Die frühe Kindheit ist ein kritisches Alter für die Entwicklung von chronischer Adipositas. Die Anhäufung von Fettgewebe während der Entwicklung und Progression der frühen Adipositas im Kindesalter tritt sowohl durch Hypertrophie als auch Hyperplasie der Adipozyten im Fettgewebe auf. Dabei ist die derzeit verbreitete Hypothese, dass die Anzahl der Adipozyten in der Kindheit bestimmt wird und während des gesamten Lebens relativ konstant bleibt, obwohl bis zu einem gewissen Grad eine ständige Erneuerung von Adipozyten durch die Proliferation und Differenzierung von im Fettgewebe vorhandenen adipogenen Vorläuferzellen stattfindet. Adipositas ist bereits in der frühen Kindheit mit Störungen in der Biologie und Funktion des weißen Fettgewebes assoziiert, einschließlich der Adipozytenhypertrophie, lokalen und systemischen inflammatorischen Prozessen, einer Remodellierung der extrazellulären Matrix und Fibrose, verstärkter Proliferation von adipogenen Vorläuferzellen und Störungen in der Adipokinsekretion. Diese Veränderungen in der Biologie und Funktion des Fettgewebes sind potentiell ursächliche Faktoren, welche zur Entwicklung von Adipositas-assoziierten Begleiterkrankungen, wie Diabetes und Herz-Kreislauf-Erkrankungen, im späteren Leben beitragen.
Abstract
Early childhood is a critical period for the development and manifestation of obesity. Accumulation of adipose tissue mass during obesity development in childhood occurs by a combination of two processes: adipocyte hypertrophy and hyperplasia. Recent results suggest that the number of adipocytes is determined during childhood and stays constant during adulthood with some adipocyte turnover taking place through proliferation and differentiation of adipose progenitor cells. Moreover, already in early childhood obesity is associated with alterations in white adipose tissue biology and function including adipocyte hypertrophy, local and systemic inflammation, remodeling of the extracellular matrix and adipose tissue fibrosis, increased proliferation of adipose progenitor cells, and alterations in adipokine secretion. This early white adipose tissue dysfunction in obese children might contribute to the development of obesity-associated diseases, such as diabetes and cardiovascular disease, later in life.
-
Literatur
- 1 Bjorntorp P. Adipose tissue distribution and function. Int J Obes 1991; 15 (Suppl. 02) 67-81
- 2 Spalding KL, Arner E, Westermark PO. et al. Dynamics of fat cell turnover in humans. Nature 2008; 453 (7196) 783-787
- 3 Brook CG, Lloyd JK, Wolf OH. Relation between age of onset of obesity and size and number of adipose cells. Br Med J 1972; 2 (5804) 25-27
- 4 Knittle JL, Timmers K, Ginsberg-Fellner F. et al. The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size. J Clin Invest 1979; 63 (02) 239-246
- 5 Hager A, Sjorstrom L, Arvidsson B. et al. Adipose tissue cellularity in obese school girls before and after dietary treatment. Am J Clin Nutr 1978; 31 (01) 68-75
- 6 Landgraf K, Rockstroh D, Wagner IV. et al. Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children. Diabetes 2015; 64 (04) 1249-1261
- 7 Kursawe R, Eszlinger M, Narayan D. et al. Cellularity and adipogenic profile of the abdominal subcutaneous adipose tissue from obese adolescents: association with insulin resistance and hepatic steatosis. Diabetes 2010; 59 (09) 2288-2296
- 8 Klöting N, Blüher M. Adipocyte dysfunction, inflammation and metabolic syndrome. Rev Endocr Metab Disord 2014; 15 (04) 277-287
- 9 Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest 2011; 121 (06) 2094-2101
- 10 Haase J, Weyer U, Immig K. et al. Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Diabetologia 2014; 57 (03) 562-571
- 11 Cinti S, Mitchell G, Barbatelli G. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46 (11) 2347-2355
- 12 Sbarbati A, Osculati F, Silvagni D. et al. Obesity and inflammation: evidence for an elementary lesion. Pediatrics 2006; 117 (01) 220-223
- 13 Tam CS, Tordjman J, Divoux A. et al. Adipose tissue remodeling in children: the link between collagen deposition and age-related adipocyte growth. J Clin Endocrinol Metab 2012; 97 (04) 1320-1327
- 14 Walker RW, Allayee H, Inserra A. et al. Macrophages and fibrosis in adipose tissue are linked to liver damage and metabolic risk in obese children. Obesity (Silver Spring) 2014; 22 (06) 1512-1519
- 15 Divoux A, Tordjman J, Lacasa D. et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 2010; 59 (11) 2817-2825
- 16 Khan T, Muise ES, Iyengar P. et al. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol 2009; 29 (06) 1575-1591
- 17 Bougneres P, Stunff CL, Pecqueur C. et al. In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity. J Clin Invest 1997; 99 (11) 2568-2573
- 18 Rutkowski JM, Stern JH, Scherer PE. The cell biology of fat expansion. J Cell Biol 2015; 208 (05) 501-512
- 19 Kursawe R, Caprio S, Giannini C. et al. Decreased transcription of ChREBP-alpha/beta isoforms in abdominal subcutaneous adipose tissue of obese adolescents with prediabetes or early type 2 diabetes: associations with insulin resistance and hyperglycemia. Diabetes 2013; 62 (03) 837-844
- 20 Kursawe R, Narayan D, Cali AM. et al. Downregulation of ADIPOQ and PPARgamma2 gene expression in subcutaneous adipose tissue of obese adolescents with hepatic steatosis. Obesity (Silver Spring) 2010; 18 (10) 1911-1917
- 21 Langin D, Dicker A, Tavernier G. et al. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes 2005; 54 (11) 3190-3197
- 22 Arner P, Spalding KL. Fat cell turnover in humans. Biochem Biophys Res Commun 2010; 396 (01) 101-104
- 23 Maumus M, Sengenes C, Decaunes P. et al. Evidence of in situ proliferation of adult adipose tissue-derived progenitor cells: influence of fat mass microenvironment and growth. J Clin Endocrinol Metab 2008; 93 (10) 4098-4106
- 24 Grohmann M, Sabin M, Holly J. et al. Characterization of differentiated subcutaneous and visceral adipose tissue from children: the influences of TNF-alpha and IGF-I. J Lipid Res 2005; 46 (01) 93-103
- 25 Haro-Mora JJ, Garcia-Escobar E, Porras N. et al. Adipose tissue characteristics related to weight z-score in childhood. Int J Endocrinol Metab 2013; 11 (02) 82-87
- 26 Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89 (06) 2548-2556
- 27 Körner A, Kratzsch J, Kiess W. Adipocytokines: leptin-the classical, resistin-the controversial, adiponectin-the promising, and more to come. Best.Pract.Res.Clin Endocrinol Metab 2005; 19 (04) 525-546
- 28 Böttner A, Kratzsch J, Müller G. et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 2004; 89 (08) 4053-4061
- 29 Kratzsch J, Lammert A, Böttner A. et al. Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence. J Clin Endocrinol Metab 2002; 87 (10) 4587-4594
- 30 Friebe D, Neef M, Erbs S. et al. Retinol binding protein 4 (RBP4) is primarily associated with adipose tissue mass in children. Int J Pediatr Obes 2011; 6 (02/02) e345-e352
- 31 Körner A, Wabitsch M, Seidel B. et al. Adiponectin expression in humans is dependent on differentiation of adipocytes and down-regulated by humoral serum components of high molecular weight. Biochem Biophys.Res Commun 2005; 337 (02) 540-550
- 32 Landgraf K, Friebe D, Ullrich T. et al. Chemerin as a Mediator between Obesity and Vascular Inflammation in Children. J Clin Endocrinol Metab 2012; 97 (04) E556-E564
- 33 Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci 2015; 36 (07) 461-470
- 34 Margetic S, Gazzola C, Pegg GG. et al. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002; 26 (11) 1407-1433
- 35 Bahceci M, Gokalp D, Bahceci S. et al. The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults?. J Endocrinol Invest 2007; 30 (03) 210-214
- 36 Hammarstedt A, Graham TE, Kahn BB. Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells. Diabetol Metab Syndr 2012; 4 (01) 42
- 37 Sabin MA, Holly JM, Shield JP. et al. Mature subcutaneous and visceral adipocyte concentrations of adiponectin are highly correlated in prepubertal children and inversely related to body mass index standard deviation score. J Clin Endocrinol Metab 2006; 91 (01) 332-335
- 38 Tam CS, Heilbronn LK, Henegar C. et al. An early inflammatory gene profile in visceral adipose tissue in children. Int J Pediatr Obes 2011; 6 (02/02) e360-e363
- 39 Aguilera CM, Gomez-Llorente C, Tofe I. et al. Genome-wide expression in visceral adipose tissue from obese prepubertal children. Int J Mol Sci 2015; 16 (04) 7723-7737
- 40 Körner A, Kiess W, Landgraf K. White Adipose Tissue Accumulation and Dysfunction in Children with Obesity. In: Freemark M. (eds). Pediatric Obesity. Contemporary Endocrinology. Humana Press; Cham: 2018