High Fat Programming Induces Glucose Intolerance in Weanling Wistar Rats

Abstract

We sought to determine whether maintenance on a high fat diet during defined periods of gestation and lactation induced glucose intolerance in weanling Wistar rats or affected food intake, weight, and glucose concentrations in mothers. Experimental groups comprised mothers and their weanling offspring maintained on a high fat diet during gestation and lactation (HFGL), during gestation only (HFG), or during lactation only (HFL). Maternal food intake, body weight, and fasting blood glucose concentrations were determined during lactation. Glucose tolerance was measured in the three-week-old weanling offspring. After overnight fasting, oral glucose tolerance tests were performed in the weanlings. Glucose was collected at (0), 10, 15, 30 and 60 min. HFGL and HFL weanlings had greater glucose concentrations compared to control weanlings at 10, 15, 30 and 60 min. For HFG weanlings, greater glucose concentrations were only found at 30 min, which normalized at 60 min. In all of the experimental groups, the highest glucose concentrations were demonstrated at 30 min, whereas the peak was achieved at 15 min in the control weanlings. Overt glucose intolerance was induced in weanlings maintained on a high fat diet throughout both gestation and lactation or throughout lactation only. Further, weanlings maintained on a high fat diet solely throughout gestation displayed milder glucose intolerance. Developmental programming with a high fat diet during defined periods of gestation and lactation induces glucose intolerance in weanling rats.

diabetes - nutrition - OGTT

References

• 1 Cerf ME, Louw J. High fat-induced programming of beta-cell development and function in neonatal and weanling offspring.. Trivandrum, Kerala, India: Transworld Research Network; 2008: 133-158
• 2 Cerf ME, Chapman CS, Muller CJ, Louw J. Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal Wistar rats.  Metabolism. 2009;  58 1787-1792
• 3 Cerf ME, Muller CJ, Du Toit DF, Louw J, Wolfe-Coote SA. Hyperglycaemia and reduced glucokinase expression in weanling offspring from dams maintained on a high-fat diet.  Br J Nutr. 2006;  95 391-396
• 4 Del Prato S, Tiengo A. The importance of first-phase insulin secretion: implications for the therapy of type 2 diabetes mellitus.  Diabetes Metab Res Rev. 2001;  17 164-174
• 5 Rooney K, Bryson J, Phuyal J, Denyer G, Caterson I, Thompson C. Creatine supplementation alters insulin secretion and glucose homeostasis in vivo.  Metabolism. 2002;  51 518-522
• 6 Stefan N, Stumvoll M, Weyer C, Bogardus C, Tataranni PA, Pratley RE. Exaggerated insulin secretion in Pima Indians and African-Americans but higher insulin resistance in Pima Indians compared to African-Americans and Caucasians.  Diabet Med. 2004;  21 1090-1095
• 7 Ferrannini E, Natali A, Bell P, Cavallo-Perin P, Lalic N, Mingrone G. Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR).  J Clin Invest. 1997;  100 1166-1173
• 8 DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM.  Diabetes. 1988;  37 667-687
• 9 Flanagan AM, Brown JL, Santiago CA, Aad PY, Spicer LJ, Spicer MT. High-fat diets promote insulin resistance through cytokine gene expression in growing female rats.  J Nutr Biochem. 2008;  19 505-513
• 10 Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN. Diet-induced type II diabetes in C57BL/6J mice.  Diabetes. 1988;  37 1163-1167
• 11 Surwit RS, Feinglos MN, Rodin J, Sutherland A, Petro AE, Opara EC, Kuhn CM, Rebuffe-Scrive M. Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice.  Metabolism. 1995;  44 645-651
• 12 Cusin I, Terrettaz J, Rohner-Jeanrenaud F, Jeanrenaud B. Metabolic consequences of hyperinsulinaemia imposed on normal rats on glucose handling by white adipose tissue, muscles and liver.  Biochem J. 1990;  267 99-103
• 13 Zambrano E, Bautista CJ, Deas M, Martinez-Samayoa PM, Gonzalez-Zamorano M, Ledesma H, Morales J, Larrea F, Nathanielsz PW. A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat.  J Physiol. 2006;  571 221-230
• 14 Cunha AC, Pereira RO, Pereira MJ, Soares Vde M, Martins MR, Teixeira MT, Souza EP, Moura AS. Long-term effects of overfeeding during lactation on insulin secretion – the role of GLUT-2.  J Nutr Biochem. 2009;  20 435-442
• 15 Heywood WE, Mian N, Milla PJ, Lindley KJ. Programming of defective rat pancreatic beta-cell function in offspring from mothers fed a low-protein diet during gestation and the suckling periods.  Clin Sci (Lond). 2004;  107 37-45
• 16 Siebel AL, Mibus A, De Blasio MJ, Westcott KT, Morris MJ, Prior L, Owens JA, Wlodek ME. Improved lactational nutrition and postnatal growth ameliorates impairment of glucose tolerance by uteroplacental insufficiency in male rat offspring.  Endocrinology. 2008;  149 3067-3076
• 17 Cerf ME, Williams K, Nkomo XI, Muller CJ, Du Toit DF, Louw J, Wolfe-Coote SA. Islet cell response in the neonatal rat after exposure to a high-fat diet during pregnancy.  Am J Physiol Regul Integr Comp Physiol. 2005;  288 1122-1128
• 18 Gluckman PD, Hanson MA. The developmental origins of the metabolic syndrome.  Trends Endocrinol Metab. 2004;  15 183-187
• 19 Gniuli D, Calcagno A, Caristo ME, Mancuso A, Macchi V, Mingrone G, Vettor R. Effects of high-fat diet exposure during fetal life on type 2 diabetes development in the progeny.  J Lipid Res. 2008;  49 1936-1945

Correspondence