Skip to main content
SpringerLink
Log in
Book cover

Type 2 Diabetes pp 43–69Cite as

Nutritional Models of Type 2 Diabetes Mellitus

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2076))

Abstract

In order to better understand the events that precede and precipitate the onset of type 2 diabetes (T2DM), several nutritional animal models have been developed. These models are generated by manipulating the diet of either the animal itself, or its mother during her pregnancy, and in comparison to traditional genetic and knock out models, have the advantage that they more accurately reflect the etiology of human T2DM. This chapter will discuss some of the most widely used nutritional models of T2DM: Diet-induced obesity (DIO) in adult rodents, and studies of offspring of mothers fed a low-protein, high-fat and/or high-sugar diet during pregnancy and/or lactation. Several common mechanisms have been identified through which these nutritional manipulations can lead to metabolic disease, including pancreatic beta-cell dysfunction, impaired insulin signaling in skeletal muscle, and the excess accumulation of visceral adipose tissue and consequent deposition of nonesterified fatty acids in peripheral tissues. In addition, there is an emerging concept that obesity/poor quality diets result in increased production and release of pro-inflammatory cytokines from adipose tissue leading to a state of chronic low-grade inflammation, and that this is likely to represent an important link between obesity/diet and metabolic dysfunction. The following chapter will discuss the most common nutritional models of T2DM in experimental animals, their application, and relationship to human etiology, and will highlight the important insights these models have provided into the pathogenesis of T2DM.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Buettner R, Scholmerich J, Bollheimer LC (2007) High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity 15:798–808

    Article  CAS  PubMed  Google Scholar 

  2. Portha B, Blondel O, Serradas P, McEvoy R, Giroix MH, Kergoat M, Bailbe D (1989) The rat models of non-insulin dependent diabetes induced by neonatal streptozotocin. Diabete Metab 15:61–75

    CAS  PubMed  Google Scholar 

  3. Bray GA (2004) Medical consequences of obesity. J Clin Endocrinol Metab 89:2583–2589

    Article  CAS  PubMed  Google Scholar 

  4. Goralski KB, Sinal CJ (2007) Type 2 diabetes and cardiovascular disease: getting to the fat of the matter. Can J Physiol Pharmacol 85:113–132

    Article  CAS  PubMed  Google Scholar 

  5. Smith SR, Lovejoy JC, Greenway F, Ryan D, deJonge L, de la Bretonne J, Volafova J, Bray GA (2001) Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism 50:425–435

    Article  CAS  PubMed  Google Scholar 

  6. Ravussin E, Smith SR (2002) Increased fat uptake, impaired fat oxidation, and failure of fat cell proliferation result in ectopic fat storage, insulin resistance, and type 2 diabetes. Ann N Y Acad Sci 967:363–378

    Article  CAS  PubMed  Google Scholar 

  7. Surwit R, Kuhn C, Cochrane C, McCubbin J, Feinglos M (1988) Diet-induced type II diabetes in C57BL/6J mice. Diabetes 37:1163–1167

    Article  CAS  PubMed  Google Scholar 

  8. Black BL, Croom J, Eisen EJ, Petro AE, Edwards CL, Surwit RS (1998) Differential effects of fat and sucrose on body composition in A/J and C57BL/6 mice. Metabolism 47:1354–1359

    Article  CAS  PubMed  Google Scholar 

  9. Roberts CK, Berger JJ, Barnard RJ (2002) Long-term effects of diet on leptin, energy intake, and activity in a model of diet-induced obesity. J Appl Physiol 93:887–893

    Article  CAS  PubMed  Google Scholar 

  10. Bayol SA, Farrington SJ, Stickland NC (2007) A maternal ‘junk food’ diet in pregnancy and lactation promotes an exacerbated taste for ‘junk food’ and a greater propensity for obesity in rat offspring. Br J Nutr 98:843–851

    Article  CAS  PubMed  Google Scholar 

  11. Taylor PD, McConnell J, Khan IY, Holemans K, Lawrence KM, Asare-Anane H, Persaud SJ, Jones PM, Petrie L, Hanson MA, Poston L (2005) Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. Am J Physiol Regul Integr Comp Physiol 288:R134–R139

    Article  CAS  PubMed  Google Scholar 

  12. Ong ZY, Wanasuria AF, Lin MZP, Hiscock J, Muhlhausler BS (2013) Chronic intake of a cafeteria diet and subsequent abstinence. Sex-specific effects on gene expression in the mesolimbic reward system. Appetite 65:189–199

    Article  PubMed  Google Scholar 

  13. Reichelt AC, Morris MJ, Westbrook RF (2014) Cafeteria diet impairs expression of sensory-specific satiety and stimulus-outcome learning. Front Psychol 5:852

    Article  PubMed Central  PubMed  Google Scholar 

  14. Hariri N, Thibault L (2010) High-fat diet-induced obesity in animal models. Nutr Res Rev 23:270–299

    Article  CAS  PubMed  Google Scholar 

  15. Flanagan AM, Brown JL, Santiago CA, Aad PY, Spicer LJ, Spicer MT (2008) High-fat diets promote insulin resistance through cytokine gene expression in growing female rats. J Nutr Biochem 19:505–513

    Article  CAS  PubMed  Google Scholar 

  16. Barbosa-da-Silva S, da Silva NC, Aguila MB, Mandarim-de-Lacerda CA (2013) Liver damage is not reversed during the lean period in diet-induced weight cycling in mice. Hepatol Res 18:12138

    Google Scholar 

  17. Flachs P, Rossmeisl M, Bryhn M, Kopecky J (2009) Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clin Sci (Lond) 116:1–16

    Article  CAS  Google Scholar 

  18. Muhlhausler BS, Cook-Johnson R, James M, Miljkovic D, Duthoit E, Gibson R (2010) Opposing effects of omega-3 and omega-6 long chain polyunsaturated fatty acids on the expression of lipogenic genes in omental and retroperitoneal adipose depots in the rat. J Nutr Metab

    Google Scholar 

  19. Ruzickova J, Rossmeisl M, Prazak T, Flachs P, Sponarova J, Veck M, Tvrzicka E, Bryhn M, Kopecky J (2004) Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue. Lipids 39:1177–1185

    Article  CAS  PubMed  Google Scholar 

  20. Massiera F, Guesnet P, Ailhaud G (2006) The crucial role of dietary n-6 polyunsaturated fatty acids in excessive adipose tissue development: relationship to childhood obesity. Nestle Nutr Workshop Ser Pediatr Program 57:235–242

    Article  CAS  PubMed  Google Scholar 

  21. Massiera F, Saint-Marc P, Seydoux J, Murata T, Kobayashi T, Narumiya S, Guesnet P, Amri E-Z, Negrel R, Ailhaud G (2003) Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? J Lipid Res 44:271–279

    Article  CAS  PubMed  Google Scholar 

  22. Semple RK, Chatterjee VK, O’Rahilly S (2006) PPAR gamma and human metabolic disease. J Clin Invest 116:581–589

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. De Caterina R, Basta G (2001) n-3 Fatty acids and the inflammatory response — biological background. Eur Heart J Suppl 3:D42–D49

    Article  Google Scholar 

  24. Chandalia M, Abate N (2007) Metabolic complications of obesity: inflated or inflamed? J Diabetes Complications 21:128–136

    Article  PubMed  Google Scholar 

  25. Malik VS, Popkin BM, Bray GA, Despres JP, Hu FB (2010) Sugar-sweetened beverages, obesity, type 2 diabetes mellitus, and cardiovascular disease risk. Circulation 121:1356–1364

    Article  PubMed Central  PubMed  Google Scholar 

  26. Romaguera D, Norat T, Wark PA, Vergnaud AC, Schulze MB, van Woudenbergh GJ, Drogan D, Amiano P, Molina-Montes E, Sanchez MJ, Balkau B, Barricarte A, Beulens JW, Clavel-Chapelon F, Crispim SP, Fagherazzi G, Franks PW, Grote VA, Huybrechts I, Key TJ, Khaw KT, Nilsson P, Overvad K, Palli D, Panico S, Quiros JR, Rolandsson O, Sacerdote C, Sieri S, Slimani N, Spijkerman AM, Tjonneland A, Tormo MJ, Tumino R, van den Berg SW, Wermeling PR, Zamara-Ros R, Feskens EJ, Langenberg C, Sharp SJ, Foroughi NG, Riboli E, Wareham NJ (2013) Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct. Diabetologia 56:1520–1530

    Article  CAS  PubMed  Google Scholar 

  27. Johnson RK, Appel LJ, Brands M, Howard BV, Lefevre M, Lustig RH, Sacks F, Steffen LM, Wylie-Rosett J (2009) Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation 120:1011–1020

    Article  CAS  PubMed  Google Scholar 

  28. Te Morenga L, Mallard S, Mann J (2012) Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. BMJ 346:e7492

    Article  Google Scholar 

  29. Willett WC, Ludwig DS (2013) Science souring on sugar. BMJ 346:e8077

    Article  CAS  PubMed  Google Scholar 

  30. McLennan W, Podger A (1998) National nutrition survey nutrient intakes and physical measurements 1995. Canberra, ACT, Australian Bureau of Statistics

    Google Scholar 

  31. Tappy L, Le KA (2010) Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 90:23–46

    Article  CAS  PubMed  Google Scholar 

  32. Douard V, Ferraris RP (2013) The role of fructose transporters in diseases linked to excessive fructose intake. J Physiol 591:401–414

    Article  CAS  PubMed  Google Scholar 

  33. Lustig RH (2013) Fructose: it’s “alcohol without the buzz”. Adv Nutr 4:226–235

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Tran LT, Yuen VG, McNeill JH (2009) The fructose-fed rat: a review on the mechanisms of fructose-induced insulin resistance and hypertension. Mol Cell Biochem 332:145–159

    Article  CAS  PubMed  Google Scholar 

  35. Pagliassotti MJ, Prach PA, Koppenhafer TA, Pan DA (1996) Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats. Am J Physiol 271:R1319–R1326

    CAS  PubMed  Google Scholar 

  36. Sheludiakova A, Rooney K, Boakes RA (2012) Metabolic and behavioural effects of sucrose and fructose/glucose drinks in the rat. Eur J Nutr 51:445–454

    Article  CAS  PubMed  Google Scholar 

  37. Chicco A, D’Alessandro ME, Karabatas L, Pastorale C, Basabe JC, Lombardo YB (2003) Muscle lipid metabolism and insulin secretion are altered in insulin-resistant rats fed a high sucrose diet. J Nutr 133:127–133

    Article  CAS  PubMed  Google Scholar 

  38. Oliveira LS, Santos DA, Barbosa-da-Silva S, Mandarim-de-Lacerda CA, Aguila MB (2014) The inflammatory profile and liver damage of a sucrose-rich diet in mice. J Nutr Biochem 25:193–200

    Article  CAS  PubMed  Google Scholar 

  39. Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi L (2003) Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J Hypertens 16:973–978

    Article  CAS  PubMed  Google Scholar 

  40. Kazumi T, Odaka H, Hozumi T, Ishida Y, Amano N, Yoshino G (1997) Effects of dietary fructose or glucose on triglyceride production and lipogenic enzyme activities in the liver of Wistar fatty rats, an animal model of NIDDM. Endocr J 44:239–245

    Article  CAS  PubMed  Google Scholar 

  41. Levin BE, Hogan S, Sullivan AC (1989) Initiation and perpetuation of obesity and obesity resistance in rats. Am J Physiol Regul Integr Comp Physiol 256:R766–R771

    Article  CAS  Google Scholar 

  42. Clegg DJ, Benoit SC, Reed JA, Woods SC, Dunn-Meynell A, Levin BE (2005) Reduced anorexic effects of insulin in obesity-prone rats fed a moderate-fat diet. Am J Physiol Regul Integr Comp Physiol 288:R981–R986

    Article  CAS  PubMed  Google Scholar 

  43. Levin BE, Dunn-Meynell AA, Balkan B, Keesey RE (1997) Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol 273:R725–R730

    Article  CAS  Google Scholar 

  44. Tkacs NC, Levin BE (2004) Obesity-prone rats have preexisting defects in their counter regulatory response to insulin-induced hypoglycemia. Am J Physiol Regul Integr Comp Physiol 287:R1110–R1115

    Article  CAS  PubMed  Google Scholar 

  45. Woods SC, Seeley RJ, Rushing PA, D’Alessio D, Tso P (2003) A controlled high-fat diet induces an obese syndrome in rats. J Nutr 133:1081–1087

    Article  CAS  PubMed  Google Scholar 

  46. Qiu L, List EO, Kopchick JJ (2005) Differentially expressed proteins in the pancreas of diet-induced diabetic mice. Mol Cell Proteomics 4:1311–1318

    Article  CAS  PubMed  Google Scholar 

  47. Corbett SW, Stern JS, Keesey RE (1986) Energy expenditure in rats with diet-induced obesity. Am J Clin Nutr 44:173–180

    Article  CAS  PubMed  Google Scholar 

  48. Yaqoob P, Sherrington EJ, Jeffery NM, Sanderson P, Harvey DJ, Newsholme EA, Calder PC (1995) Comparison of the effects of a range of dietary lipids upon serum and tissue lipid composition in the rat. Int J Biochem Cell Biol 27:297–310

    Article  CAS  PubMed  Google Scholar 

  49. Dandona P, Aljada A, Bandyopadhyay A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25:4–7

    Article  CAS  PubMed  Google Scholar 

  50. Higa TS, Spinola AV, Fonseca-Alaniz MH, Evangelista FSA (2014) Comparison between cafeteria and high-fat diets in the induction of metabolic dysfunction in mice. Int J Physiol Pathophysiol Pharmacol 6:47–54

    PubMed Central  PubMed  Google Scholar 

  51. Wassink AM, Olijhoek JK, Visseren FL (2007) The metabolic syndrome: metabolic changes with vascular consequences. Eur J Clin Invest 37:8–17

    Article  CAS  PubMed  Google Scholar 

  52. Shafrir E, Ziv E, Kalman R (2006) Nutritionally induced diabetes in desert rodents as models of type 2 diabetes: acomys cahirinus (spiny mice) and Psammomys obesus (desert gerbil). ILAR J 47:212–224

    Article  CAS  PubMed  Google Scholar 

  53. Kaiser N, Nesher R, Donath MY, Fraenkel M, Behar V, Magnan C, Ktorza A, Cerasi E, Leibowitz G (2005) Psammomys obesus, a model for environment-gene interactions in type 2 diabetes. Diabetes 54:S137–S144

    Article  CAS  PubMed  Google Scholar 

  54. Maislos M, Medvedovskv V, Sztarkier I, Yaari A, Sikuler E (2006) Psammomys obesus (sand rat), a new animal model of non-alcoholic fatty liver disease. Diabetes Res Clin Pract 72:1–5

    Article  CAS  PubMed  Google Scholar 

  55. Barker DJP, Bull AR, Osmond C, Simmonds SJ (1990) Fetal and placental size and risk of hypertension in adult life. Br Med J 301:259–262

    Article  CAS  Google Scholar 

  56. Hales CN, Barker DJP (2001) The thrifty phenotype hypothesis. Br Med Bull 60:5–20

    Article  CAS  PubMed  Google Scholar 

  57. McMillen IC, Robinson JS (2005) Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85:571–633

    Article  CAS  PubMed  Google Scholar 

  58. Ravelli AC, van der Meulen JH, Osmond C, Barker DJ, Bleker OP (1999) Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 70:811–816

    Article  CAS  PubMed  Google Scholar 

  59. Ravelli ACJ, van der Meulen JHP, Michels RPJ, Osmond C, Barker DJP, Hales CN, Bleker OP (1998) Glucose tolerance in adults after prenatal exposure to famine. Lancet 351:173–177

    Article  CAS  PubMed  Google Scholar 

  60. Pettit DJ, Knowler WC (1998) Long-term effects of the intrauterine environment, birth weight, and breast-feeding in Pima Indians. Diabetes Care 21:B138–B141

    Article  Google Scholar 

  61. Rkhzay-Jaf J, O’Dowd JF, Stocker CJ (2012) Maternal obesity and the fetal origins of the metabolic syndrome. Curr Cardiovasc Risk Rep 6:487–495

    Article  PubMed Central  PubMed  Google Scholar 

  62. Muhlhausler BS, Ong ZY (2011) The fetal origins of obesity: early origins of altered food intake. Endocr Metab Immune Disord Drug Targets 11:189–197

    Article  CAS  PubMed  Google Scholar 

  63. Bavdekar A, Yajnik C, Fall C, Bapat S, Pandit A, Deshpande V, Bhave S, Kellingray S, Joglekar C (1999) Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both? Diabetes 48:2422–2429

    Article  CAS  PubMed  Google Scholar 

  64. McMillen IC, Adam CL, Muhlhausler BS (2005) Early origins of obesity: programming the appetite regulatory system. J Physiol 565:9–17

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Hales CN, Barker DJP (2001) The thrifty phenotype hypothesis: type 2 diabetes. Br Med Bull 60:5–20

    Article  CAS  PubMed  Google Scholar 

  66. Holemans K, Verhaeghe J, Dequeker J, Van Assche FA (1996) Insulin sensitivity in adult female rats subjected to malnutrition during the perinatal period. J Soc Gynecol Investig 3:71–77

    CAS  PubMed  Google Scholar 

  67. Thompson NM, Norman AM, Donkin SS, Shankar RR, Vickers MH, Miles JL, Breier BH (2007) Prenatal and postnatal pathways to obesity: different underlying mechanisms, different metabolic outcomes. Endocrinol Metab Clin North Am 148:2345–2354

    CAS  Google Scholar 

  68. Ozanne SE (2001) Metabolic programming in animals: type 2 diabetes. Br Med Bull 60:143–152

    Article  CAS  PubMed  Google Scholar 

  69. Ozanne SE, Jensen CB, Tingey KJ, Storgaard H, Madsbad S, Vaag AA (2005) Low birthweight is associated with specific changes in muscle insulin-signalling protein expression. Diabetologia 48:547–552

    Article  CAS  PubMed  Google Scholar 

  70. Hales CN, Desai M, Ozanne SE, Crowther NJ (1996) Fishing in the stream of diabetes: from measuring insulin to the control of fetal organogenesis. Biochem Soc Trans 24:341–350

    Article  CAS  PubMed  Google Scholar 

  71. Petry CJ, Ozanne SE, Wang CL, Hales CN (1997) Early protein restriction and obesity independently induce hypertension in 1-year-old rats. Clin Sci (Lond) 93:147–152

    Article  CAS  Google Scholar 

  72. Snoeck A, Remacle C, Reusens B, Hoet JJ (1990) Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biol Neonate 57:107–118

    Article  CAS  PubMed  Google Scholar 

  73. Ozanne SE, Smith GD, Tikerpae J, Hales CN (1996) Altered regulation of hepatic glucose output in the male offspring of protein-malnourished rat dams. Am J Physiol Endocrinol Metab 270:E559–E564

    Article  CAS  Google Scholar 

  74. Ozanne SE, Nave BT, Wang CL, Shepherd PR, Prins J, Smith GD (1997) Poor fetal nutrition causes long-term changes in expression of insulin signaling components in adipocytes. Am J Physiol Endocrinol Metab 273:E46–E51

    Article  CAS  Google Scholar 

  75. Ozanne SE, Wang CL, Coleman N, Smith GD (1996) Altered muscle insulin sensitivity in the male offspring of protein-malnourished rats. Am J Physiol Endocrinol Metab 271:E1128–E1134

    Article  CAS  Google Scholar 

  76. Ozanne SE, Olsen GS, Hansen LL, Tingey KJ, Nave BT, Wang CL, Hartil K, Petry CJ, Buckley AJ, Mosthaf-Seedorf L (2003) Early growth restriction leads to down regulation of protein kinase C zeta and insulin resistance in skeletal muscle. J Endocrinol 177:235–241

    Article  CAS  PubMed  Google Scholar 

  77. Wadley GD, Siebel AL, Cooney GJ, McConell GK, Wlodek ME, Owens JA (2008) Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult rat. Am J Physiol Endocrinol Metab 294:E861–E869

    Article  CAS  PubMed  Google Scholar 

  78. Siebel AL, Mibus A, De Blasio MJ, Westcott KT, Morris MJ, Prior L, Owens JA, Wlodek ME (2008) Improved lactational nutrition and postnatal growth ameliorates impairment of glucose tolerance by uteroplacental insufficiency in male rat offspring. Endocrinology 149:3067–3076

    Article  CAS  PubMed  Google Scholar 

  79. Poston L (2011) Intergenerational transmission of insulin resistance and type 2 diabetes. Prog Biophys Mol Biol 106:315–322

    Article  CAS  PubMed  Google Scholar 

  80. Srinivasan M, Katewa SD, Palaniyappan A, Pandya JD, Patel MS (2006) Maternal high-fat diet consumption results in fetal malprogramming predisposing to the onset of metabolic syndrome-like phenotype in adulthood. Am J Physiol Endocrinol Metab 291:E792–E799

    Article  CAS  PubMed  Google Scholar 

  81. Cerf ME, Muller CJ, Du Toit DF, Louw J, Wolfe-Coote SA (2006) Hyperglycaemia and reduced glucokinase expression in weanling offspring from dams maintained on a high-fat diet. Br J Nutr 95:391–396

    Article  CAS  PubMed  Google Scholar 

  82. Muhlhausler BS, Adam CL, Findlay PA, Duffield JA, McMillen IC (2006) Increased maternal nutrition alters development of the appetite-regulating network in the brain. FASEB J 20:1257–1259

    Article  CAS  PubMed  Google Scholar 

  83. Samuelsson A-M, Matthews PA, Argenton M, Christie MR, McConnell JM, Jansen EHJM, Piersma AH, Ozanne SE, Twinn DF, Remacle C, Rowlerson A, Poston L, Taylor PD (2008) Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension 51:383–392

    Article  CAS  PubMed  Google Scholar 

  84. Muhlhausler BS, Roberts CT, McFarlane JR, Kauter KG, McMillen IC (2002) Fetal leptin is a signal of fat mass independent of maternal nutrition in ewes fed at or above maintenance energy requirements. Biol Reprod 67:493–499

    Article  CAS  PubMed  Google Scholar 

  85. Bruce KD, Cagampang FR, Argenton M, Zhang J, Ethirajan PL, Burdge GC, Bateman AC, Clough GF, Poston L, Hanson MA, McConnell JM, Byrne CD (2009) Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression. Hepatology 50:1796–1808

    Article  CAS  PubMed  Google Scholar 

  86. Srinivasan M, Aalinkeel R, Song F, Mitrani P, Pandya JD, Strutt B, Hill DJ, Patel MS (2006) Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype. Am J Physiol Endocrinol Metab 290:E129–E134

    Article  CAS  PubMed  Google Scholar 

  87. Cerf ME, Williams K, Chapman CS, Louw J (2007) Compromised beta-cell development and beta-cell dysfunction in weanling offspring from dams maintained on a high-fat diet during gestation. Pancreas 34:347–353

    Article  CAS  PubMed  Google Scholar 

  88. McCurdy CE, Bishop JM, Williams SM, Grayson BE, Smith MS, Friedman JE, Grove KL (2009) Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest 119:323–335

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Ailhaud G, Massiera F, Weill P, Legrand P, Alessandri JM, Guesnet P (2006) Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity. Prog Lipid Res 45:203–236

    Article  CAS  PubMed  Google Scholar 

  90. Muhlhausler BS, Ailhaud GP (2013) Omega-6 polyunsaturated fatty acids and the early origins of obesity. Curr Opin Endocrinol Diabetes Obes 20:56–61

    Article  CAS  PubMed  Google Scholar 

  91. Massiera F, Barbry P, Guesnet P, Joly A, Luquet S, Moreilhon-Brest C, Mohsen-Kanson T, Amri E-Z, Ailhaud G (2010) A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations. J Lipid Res 51:2352–2361

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Muhlhausler BS, Gibson RA, Makrides M (2011) The effect of maternal omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation during pregnancy and/or lactation on body fat mass in the offspring: a systematic review of animal studies. Prostaglandins Leukot Essent Fatty Acids 85:83–88

    Article  CAS  PubMed  Google Scholar 

  93. Muhlhausler BS, Gibson RA, Makrides M (2010) Effect of long-chain polyunsaturated fatty acid supplementation during pregnancy or lactation on infant and child body composition: a systematic review. Am J Clin Nutr 92:857–863

    Article  CAS  PubMed  Google Scholar 

  94. Muhlhausler BS, Miljkovic D, Fong L, Xian CJ, Duthoit E, Gibson RA (2011) Maternal omega-3 supplementation increases fat mass in male and female rat offspring. Front Genet 2:48

    Article  PubMed Central  PubMed  Google Scholar 

  95. Chen L, Hu FB, Yeung E, Willett W, Zhang C (2009) Prospective study of pre-gravid sugar-sweetened beverage consumption and the risk of gestational diabetes mellitus. Diabetes Care 32:2236–2241

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Phelan S, Hart C, Phipps M, Abrams B, Schaffner A, Adams A, Wing R (2011) Maternal behaviors during pregnancy impact offspring obesity risk. Exp Diabetes Res 985139:26

    Google Scholar 

  97. Toop CR, Muhlhausler BS, O’Dea K, Gentili S (2014) Consumption of sucrose, but not high fructose corn syrup, leads to increased adiposity and dyslipidaemia in the pregnant and lactating rat. J Dev Orig Health Dis 19:1–9

    Google Scholar 

  98. Goran MI, Dumke K, Bouret SG, Kayser B, Walker RW, Blumberg B (2013) The obesogenic effect of high fructose exposure during early development. Nat Rev Endocrinol 9:494–500

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Sloboda DM, Li M, Patel R, Clayton ZE, Yap C, Vickers MH (2014) Early life exposure to fructose and offspring phenotype: implications for long term metabolic homeostasis. J Obesity 203474:23

    Google Scholar 

  100. Vickers MH, Clayton ZE, Yap C, Sloboda DM (2011) Maternal fructose intake during pregnancy and lactation alters placental growth and leads to sex-specific changes in fetal and neonatal endocrine function. Endocrinology 152:1378–1387

    Article  CAS  PubMed  Google Scholar 

  101. Mukai Y, Kumazawa M, Sato S (2013) Fructose intake during pregnancy up-regulates the expression of maternal and fetal hepatic sterol regulatory element-binding protein-1c in rats. Endocrine 44:79–86

    Article  CAS  PubMed  Google Scholar 

  102. Rodriguez L, Panadero MI, Roglans N, Otero P, Alvarez-Millan JJ, Laguna JC, Bocos C (2013) Fructose during pregnancy affects maternal and fetal leptin signaling. J Nutr Biochem 24:1709–1716

    Article  CAS  PubMed  Google Scholar 

  103. Samuelsson AM, Matthews PA, Jansen E, Taylor PD, Poston L (2013) Sucrose feeding in mouse pregnancy leads to hypertension, and sex-linked obesity and insulin resistance in female offspring. Front Physiol 4:14

    Article  PubMed Central  PubMed  Google Scholar 

  104. Regnault TR, Gentili S, Sarr O, Toop CR, Sloboda DM (2013) Fructose, pregnancy and later life impacts. Clin Exp Pharmacol Physiol 40:824–837

    Article  CAS  PubMed  Google Scholar 

  105. Muhlhausler BS, Duffield JA, McMillen IC (2007) Increased maternal nutrition stimulates peroxisome proliferator activated receptor-{gamma} (PPAR{gamma}), adiponectin and leptin mRNA expression in adipose tissue before birth. Endocrinology 148:878–885

    Article  CAS  PubMed  Google Scholar 

  106. Kasser TR, Martin RJ, Allen CE (1981) Effect of gestational alloxan diabetes and fasting on fetal lipogenesis and lipid deposition in pigs. Biol Neonate 40:105–112

    Article  CAS  PubMed  Google Scholar 

  107. Ezekwe MO, Martin RJ (1980) The effects of maternal alloxan diabetes on body composition, liver enzymes and metabolism and serum metabolites and hormones of fetal pigs. Horm Metab Res 12:136–139

    Article  CAS  PubMed  Google Scholar 

  108. Bayol SA, Simbi BH, Bertrand JA, Stickland NC (2008) Offspring from mothers fed a ‘junk food’ diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females. J Physiol 586:3219–3230

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  109. Muhlhausler B, Smith SR (2009) Early-life origins of metabolic dysfunction: role of the adipocyte. Trends Endocrinol Metab 20:51–57

    Article  CAS  PubMed  Google Scholar 

  110. Padoan A, Rigano S, Ferrazzi E, Beaty BL, Battaglia FC, Galan HL (2004) Differences in fat and lean mass proportions in normal and growth-restricted fetuses. Am J Obstet Gynecol 191:1459–1464

    Article  PubMed  Google Scholar 

  111. Crescenzo R, Samec S, Antic V, Rohner-Jeanrenaud F, Seydoux J, Montani J-P, Dulloo AG (2003) A role for suppressed thermogenesis favoring catch-up fat in the pathophysiology of catch-up growth. Acta Paediatr 52:1090–1097

    CAS  Google Scholar 

  112. Ibanez L, Ong K, Dunger DB, de Zegher F (2006) Early development of aiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children. J Clin Endocrinol Metab 91:2153–2158

    Article  CAS  PubMed  Google Scholar 

  113. Jaquet D, Gaboriau A, Czernichow P, Levy-Marchal C (2000) Insulin resistance early in adulthood in subjects born with intrauterine growth retardation. J Clin Endocrinol Metab 85:1401–1406

    CAS  PubMed  Google Scholar 

  114. De Blasio MJ, Gatford KL, McMillen IC, Robinson JS, Owens JA (2006) Placental restriction of fetal growth increases insulin action, growth and adiposity in the young lamb. Endocrinology 148:1350–1358

    Article  CAS  PubMed  Google Scholar 

  115. De Blasio MJ, Gatford KL, Robinson JS, Owens JA (2007) Placental restriction of fetal growth reduces size at birth and alters postnatal growth, feeding activity, and adiposity in the young lamb. Am J Physiol Regul Integr Comp Physiol 292:R875–R886

    Article  CAS  PubMed  Google Scholar 

  116. Ozanne SE (2001) Metabolic programming in animals. Br Med Bull 60:143–152

    Article  CAS  PubMed  Google Scholar 

  117. Kind KL, Clifton PM, Grant PA, Owens PC, Sohlstrom A, Roberts CT, Robinson JS, Owens JA (2003) Effect of maternal feed restriction during pregnancy on glucose tolerance in the adult guinea pig. Am J Physiol Regul Integr Comp Physiol 284:R140–R152

    Article  CAS  PubMed  Google Scholar 

  118. Alexander G (1978) Quantitative development of adipose tissue in foetal sheep. Aust J Biol Sci 31:489–503

    Article  CAS  PubMed  Google Scholar 

  119. Merklin RJ (1973) Growth and distribution of human fetal brown fat. Anat Res 178:637–646

    Article  Google Scholar 

  120. Højlund K, Mogensen M, Sahlin K, Beck-Nielsen H (2008) Mitochondrial dysfunction in type 2 diabetes and obesity. Endocrinol Metab Clin North Am 37:713–731

    Article  CAS  PubMed  Google Scholar 

  121. Howie GJ, Sloboda DM, Reynolds CM, Vickers MH (2013) Timing of maternal exposure to a high fat diet and development of obesity and hyperinsulinemia in male rat offspring: same metabolic phenotype, different developmental pathways? J Nutr Metab 517384:13

    Google Scholar 

  122. Palmer AC (2011) Nutritionally mediated programming of the developing immune system. Adv Nutr 2:377–395

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  123. Zhu MJ, Du M, Nathanielsz PW, Ford SP (2010) Maternal obesity up-regulates inflammatory signaling pathways and enhances cytokine expression in the mid-gestation sheep placenta. Placenta 31:387–391

    Article  CAS  PubMed  Google Scholar 

  124. Murabayashi N, Sugiyama T, Zhang L, Kamimoto Y, Umekawa T, Ma N, Sagawa N (2013) Maternal high-fat diets cause insulin resistance through inflammatory changes in fetal adipose tissue. Eur J Obstet Gynecol Reprod Biol 169:39–44

    Article  CAS  PubMed  Google Scholar 

  125. Junien C, Gallou-Kabani C, Vigé A, Gross MS (2005) Nutritional epigenomics: consequences of unbalanced diets on epigenetics processes of programming during lifespan and between generations. Ann Endocrinol (Paris) 66:S19–S28

    Article  Google Scholar 

  126. Gallou-Kabani C, Junien C (2005) Nutritional epigenomics of metabolic syndrome: new perspective against the epidemic. Diabetes 54:1899–1906

    Article  CAS  PubMed  Google Scholar 

  127. Waterland RA, Travisano M, Tahiliani KG, Rached MT, Mirza S (2008) Methyl donor supplementation prevents transgenerational amplification of obesity. Int J Obes (Lond) 32:1373–1379

    Article  CAS  Google Scholar 

  128. Burdge GC, Hanson MA, Slater-Jefferies JL, Lillycrop KA (2007) Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life? Br J Nutr 97:1036–1046

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  129. Burdge GC, Slater-Jefferies J, Torrens C, Phillips ES, Hanson MA, Lillycrop KA (2007) Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr 97:435–439

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  130. Tobi EW, Slagboom PE, van Dongen J, Kremer D, Stein AD, Putter H, Heijmans BT, Lumey LH (2012) Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19. PLoS One 7:30

    Article  CAS  Google Scholar 

  131. Hanley B, Dijane J, Fewtrell M, Grynberg A, Hummel S, Junien C, Koletzko B, Lewis S, Renz H, Symonds M, Gros M, Harthoorn L, Mace K, Samuels F, van Der Beek EM (2010) Metabolic imprinting, programming and epigenetics – a review of present priorities and future opportunities. Br J Nutr 104:S1–S25

    Article  CAS  PubMed  Google Scholar 

  132. Heerwagen MJR, Miller MR, Barbour LA, Friedman JE (2010) Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol 299:R711–R722

    CAS  Google Scholar 

  133. Li CC, Maloney CA, Cropley JE, Suter CM (2010) Epigenetic programming by maternal nutrition: shaping future generations. Epigenomics 2:539–549

    Article  CAS  PubMed  Google Scholar 

  134. Li CC, Young PE, Maloney CA, Eaton SA, Cowley MJ, Buckland ME, Preiss T, Henstridge DC, Cooney GJ, Febbraio MA, Martin DI, Cropley JE, Suter CM (2013) Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice. Epigenetics 8:602

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  135. Haslam DW, James WP (2005) Obesity. Lancet 366:1197–1209

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

BSM is supported by a Career Development Fellowship from the National Health and Medical Research Council of Australia (NHMRC).

Author information

Authors and Affiliations

  1. Food and Nutrition Research Group, Department of Food and Wine Sciences, School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, SA, Australia

    Beverly Sara Mühlhäusler

  2. FOODplus Research Centre, School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, SA, Australia

    Beverly Sara Mühlhäusler

  3. CSIRO, Health and Biosecurity, Adelaide, SA, Australia

    Beverly Sara Mühlhäusler

  4. Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia

    Carla Toop & Sheridan Gentili

Authors
  1. Beverly Sara Mühlhäusler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carla Toop
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sheridan Gentili
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Beverly Sara Mühlhäusler .

Editor information

Editors and Affiliations

  1. Medical School, University of Buckingham, Buckingham, Buckinghamshire, UK

    Claire J. Stocker

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Mühlhäusler, B.S., Toop, C., Gentili, S. (2020). Nutritional Models of Type 2 Diabetes Mellitus. In: Stocker, C. (eds) Type 2 Diabetes. Methods in Molecular Biology, vol 2076. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9882-1_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9882-1_3

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9880-7

  • Online ISBN: 978-1-4939-9882-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation