Adipositas - Ursachen, Folgeerkrankungen, Therapie 2015; 09(03): 146-150
DOI: 10.1055/s-0037-1618930
Übersichtsarbeit
Schattauer GmbH

Kalorische Restriktion und Intervall-Fasten schützen durch Veränderungen des Leberfettstoffwechsels vor Typ-2-Diabetes

Ergebnisse aus MausstudienCaloric restriction and intermittent fasting protect from type 2 diabetes by alterations in hepatic lipid metabolismResults from mouse studies
C. Baumeier
1   Deutsches Institut für Ernährungsforschung (DIfE), Abteilung Experimentelle Diabetologie, Prof. Dr. Annette Schürmann, Potsdam-Rehbrücke, Deutschland
,
R.W. Schwenk
1   Deutsches Institut für Ernährungsforschung (DIfE), Abteilung Experimentelle Diabetologie, Prof. Dr. Annette Schürmann, Potsdam-Rehbrücke, Deutschland
,
A. Schürmann
1   Deutsches Institut für Ernährungsforschung (DIfE), Abteilung Experimentelle Diabetologie, Prof. Dr. Annette Schürmann, Potsdam-Rehbrücke, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
22 December 2017 (online)

Zusammenfassung

In Anbetracht der steigenden Prävalenz von Adipositas und seinen Komorbiditäten wie Typ-2-Diabetes (T2D) ist es von besonderer Bedeutung, adäquate Präventions- und Therapieverfahren zu entwickeln. Interventionen, wie kalorische Restriktion und Intervall- Fasten, zeigten in der Basistherapie des T2D bereits Erfolge, wobei genaue Wirkmechanismen dieser Ansätze noch nicht vollständig verstanden sind. Zur Klärung der molekularen Effekte des Fastens wurden adipöse Mäuse, die eine genetische Prädisposition für T2D besitzen, einer kalorischen Restriktion und einem Intervall-Fasten unterzogen. Sowohl eine Verminderung der Nahrungszufuhr von 10 % als auch die Fütterung an nur jedem zweiten Tag resultierten in einer Reduktion des Körpergewichts und einem kompletten Schutz vor einer Hyperglykämie. Das Intervall- Fasten verbesserte zudem die Insulinsensitivität, was mit einer veränderten Zusammensetzung Lipidtropfen-assoziierter Proteine sowie der Reduktion von Diacylglycerinen in der Leber assoziiert war. Demnach verbessert Fasten den Lipidstoffwechsel und die Insulinsensitivität und führt zu Veränderungen der hepatischen Lipidtropfen-Komposition. Ob letzteres direkt zur Reduktion von lipotoxischen Diacylglycerinen und zum Schutz vor T2D beiträgt, müssen zukünftige Studien zeigen.

Summary

In light of the increasing prevalence of obesity and its comorbidities such as type 2 diabetes (T2D) it is of particular interest to develop adequate prevention and treatment strategies. Interventions such as caloric restriction and intermittent fasting are essential approaches in the basal therapy of T2D. As detailed mechanisms of such therapies are poorly understood, effects of caloric restriction and intermittent fasting were analyzed in obese mice which exhibit a genetic predisposition for T2D. Both interventions resulted in reduced body weight and prevention of hyperglycemia. Moreover, intermittent fasting improved insulin sensitivity, which was associated with altered lipid droplet protein composition and reduced levels of diacylglycerols in the liver. Thus, fasting improves lipid metabolism and insulin sensitivity and causes changes in hepatic lipid droplet composition. Whether the alteration of the pattern of lipid droplet proteins directly contributes to a reduction of lipotoxic diacylglycerols and to protection from T2D has to be elucidated in future studies.

 
  • Literatur

  • 1 WHO. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. WHO technical report series. 2000 894. i–xii, 1–253.
  • 2 Destatis Statistisches Bundesamt. Pressemitteilung. Nr. 386 vom 05. 11. 2014. 2014.
  • 3 WHO. Diabetes. Fact sheet. N°312. 2015
  • 4 Stefan N, Kantartzis K, Häring H-U. Causes and metabolic consequences of Fatty liver. Endocrine reviews 2008; 29 (07) 939-960.
  • 5 Nationale Versorgungsleitlinie Therapie des Typ-2-Diabetes – Langfassung. Bundesärzte-kammer (BÄK), Kassenärztliche Bundesvereini-gung (KBV), Arbeitsgemeinschaft der Wissen-schaftlichen Medizinischen Fachgesellschaften (AWMF). 2013; 01 (04) 1-297.
  • 6 Li G, Zhang P, Wang J. et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet 2008; 371 9626 1783-1789.
  • 7 Knowler WC. et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Preven- tion Program Outcomes Study. Lancet 2009; 374 9702 1677-1686.
  • 8 Wing RR. et al. Benefits of modest weight loss in improving cardiovascular risk factors in over-weight and obese individuals with type 2 diabetes. Diabetes care 2011; 34 (07) 1481-1486.
  • 9 Lindström J. et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention. Lancet 2006; 368 9548 1673-1679.
  • 10 Tuomilehto J. et al. Long-term benefits from life-style interventions for type 2 diabetes prevention: time to expand the efforts. Diab Care 2011; 34: S210-214.
  • 11 Bassi N, Karagodin I, Wang S. et al. Lifestyle modification for metabolic syndrome: a systematic review. The Am J Med 2014; 127 (12) 1242 e1–10.
  • 12 Tuomilehto J, Lindström J, Eriksson JG. et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. NEJM 2001; 344 (18) 1343-1350.
  • 13 Mozaffarian D, Kamineni A, Carnethon M. et al. Lifestyle risk factors and new-onset diabetes melli- tus in older adults: the cardiovascular health study. Archives Internal Med 2009; 169 (08) 798-807.
  • 14 Yamaoka K, Tango T. Efficacy of lifestyle education to prevent type 2 diabetes. Diabetes care 2005; 28 (11) 2780-2786.
  • 15 Anderson RM, Shanmuganayagam D, Weindruch R. Caloric restriction and aging: studies in mice and monkeys. Toxicol Pathol 2009; 37 (01) 47-51.
  • 16 Mattison JA. et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 2012; 489 7415 318-321.
  • 17 Park SY. et al. Calorie restriction improves whole- body glucose disposal and insulin resistance in association with the increased adipocyte-specific GLUT4 expression in Otsuka Long-Evans Tokus- hima fatty rats. Arch Biochem Biophys 2005; 436 (02) 276-284.
  • 18 Fontana L, Klein S. Aging, Adiposity, and Calorie Restriction. JAMA 2007; 297 (09) 986-994.
  • 19 Fontana L, Partridge L, Longo VD. Extending healthy life span – from yeast to humans. Science 2010; 328 5976 321-326.
  • 20 Weiss EP. et al. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake. Am J Clin Nutr 2006; 84 (05) 1033-1042.
  • 21 Drenick EJ, Simmons F, Murphy JF. Effect on he- patic morphology of treatment of obesity by fasting, reducing diets and small-bowel bypass. NEJM 1970; 282 (15) 829-834.
  • 22 Huang MA. et al. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis. Am J Gastroenterol 2005; 100 (05) 1072-1081.
  • 23 Vitola BE. et al. Weight loss reduces liver fat and improves hepatic and skeletal muscle insulin sensi- tivity in obese adolescents. Obesity 2009; 17 (09) 1744-1748.
  • 24 Anson RM, Guo Z, De Cabo R. et al. Intermittent fasting dissociates beneficial effects of dietary re- striction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Nat Acad Sci 2003; 100 (10) 6216-6220.
  • 25 Pedersen CR. et al. Intermittent feeding and fasting reduces diabetes incidence in BB rats. Autoimmunity 1999; 30 (04) 243-250.
  • 26 Wan R. et al. Intermittent fasting and dietary supplementation with 2–deoxy-D-glucose improve functional and metabolic cardiovascular risk factors in rats. FASEB J 2003 (1): 1133-1134.
  • 27 Longo VD, Mattson MP. Fasting: molecular mech-anisms and clinical applications. Cell metabolism 2014; 19 (02) 181-192.
  • 28 Heilbronn LK, Smith SR, Martin CK. et al. Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. Am J Clin Nutr 2005; 81 (01) 69-73.
  • 29 Halberg N, Henriksen M, So N. et al. Effect of intermittent fasting and refeeding on insulin action in healthy men. J Apl Physiol 2005; 2128-2136.
  • 30 Varady KA, Bhutani S. et al. Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults. Am J Clin Nutr 2009; 90 (05) 1138-1143.
  • 31 Patterson RE, Laughlin GA, Sears DD. et al. Intermittent Fasting and Human Metabolic Health. J Acad Nutr Diet 2015; 115: 1203-1212.
  • 32 Den Boer M, Voshol PJ, Kuipers F. et al. Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal models. Arteriosclerosis, Thrombosis, and Vasc Biol 2004; 24 (04) 644-649.
  • 33 Belkacemi L, Selselet-Attou G, Bulur N. et al. Intermittent fasting modulation of the diabetic syn- drome in sand rats. III. Post-mortem investigations. Int J Molecular Med 2011; 27 (01) 95-102.
  • 34 Hatori M, Vollmers C, Zarrinpar A. et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell metabol 2012; 15 (06) 848-860.
  • 35 Baumeier C. et al. Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice. Biochimica et biophysica acta 2015; 1851 (05) 566-576.
  • 36 Erion DM, Shulman GI. Diacylglycerol-mediated insulin resistance. Nat Med 2010; 16 (04) 400-402.
  • 37 Birkenfeld AL, Shulman GI. Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology 2014; 59 (02) 713-723.
  • 38 Jornayvaz FR, Shulman GI. Diacylglycerol activation of protein kinase Cε and hepatic insulin resistance. Cell metabolism 2012; 15 (05) 574-584.
  • 39 Greenberg AS. et al. The role of lipid droplets in metabolic disease in rodents and humans. J Clin Investig 2011; 121 (06) 2102-2110.