Skip to main content
Top
Published in: European Journal of Nutrition 3/2016

01-04-2016 | Original Contribution

Fasting for 3 days during the suckling–weaning transient period in male rats induces metabolic abnormalities in the liver and is associated with impaired glucose tolerance in adulthood

Authors: Misa Ikeda, Kazue Honma, Kazuki Mochizuki, Toshinao Goda

Published in: European Journal of Nutrition | Issue 3/2016

Login to get access

Abstract

Purpose

Recent studies suggest that nutritional status during developmental periods is associated with subsequent development of metabolic abnormalities. In this study, we examined whether malnutrition by fasting for 3 days during the suckling–weaning transient period induces subsequent development of metabolic abnormalities in rats.

Methods

Male Sprague–Dawley rats were fasted for 3 days during the suckling–weaning transient period. They are subsequently fed a high-fat, high-sucrose (HF) or low-fat, high-starch (LF) diet for 14 weeks from 17 weeks of age, and the liver and blood samples were collected for measuring mRNA and protein levels of metabolic genes and blood concentrations of glucose and insulin, respectively.

Results

Fasting for 3 days during the suckling–weaning transient period induced impaired glucose tolerance in rats fed the LF diet in adulthood. Liver triglycerides in rats fed the HF diet in adulthood increased to 140 % in rats fasted for 3 days during the suckling–weaning transient period compared with those non-fasted. Furthermore, liver expression of FBP1 and ACCα genes in adult rats fed the LF diet increased to 125 and 145 %, respectively, in rats fasted for 3 days during the suckling–weaning transient period compared to non-fasted rats. PEPCK1 protein expression levels in rats fed the LF diet were higher in rats fasted for 3 days during the suckling–weaning transient period than in non-fasted rats.

Conclusion

Fasting for 3 days in rats during the suckling–weaning transient period enhances metabolic abnormalities in animals fed a HF or LF diet in adulthood by confounding metabolism of lipid and sugar in the liver.
Literature
1.
go back to reference Manrique C, DeMarco VG, Aroor AR, Mugerfeld I, Garro M, Habibi J, Hayden MR, Sowers JR (2013) Obesity and insulin resistance induce early development of diastolic dysfunction in young female mice fed a Western diet. Endocrinology 154(10):3632–3642. doi:10.1210/en.2013-1256 CrossRef Manrique C, DeMarco VG, Aroor AR, Mugerfeld I, Garro M, Habibi J, Hayden MR, Sowers JR (2013) Obesity and insulin resistance induce early development of diastolic dysfunction in young female mice fed a Western diet. Endocrinology 154(10):3632–3642. doi:10.​1210/​en.​2013-1256 CrossRef
3.
go back to reference Jazet IM, Pijl H, Meinders AE (2003) Adipose tissue as an endocrine organ: impact on insulin resistance. Neth J Med 61(6):194–212 Jazet IM, Pijl H, Meinders AE (2003) Adipose tissue as an endocrine organ: impact on insulin resistance. Neth J Med 61(6):194–212
5.
go back to reference Nishi Y, Fukushima M, Suzuki H, Mitsui R, Ueda N, Taniguchi A, Nakai Y, Kawakita T, Kurose T, Seino Y, Yamada Y (2005) Insulin secretion and insulin sensitivity in Japanese subjects with impaired fasting glucose and isolated fasting hyperglycemia. Diabetes Res Clin Pract 70(1):46–52. doi:10.1016/j.diabres.2005.02.015 CrossRef Nishi Y, Fukushima M, Suzuki H, Mitsui R, Ueda N, Taniguchi A, Nakai Y, Kawakita T, Kurose T, Seino Y, Yamada Y (2005) Insulin secretion and insulin sensitivity in Japanese subjects with impaired fasting glucose and isolated fasting hyperglycemia. Diabetes Res Clin Pract 70(1):46–52. doi:10.​1016/​j.​diabres.​2005.​02.​015 CrossRef
6.
go back to reference Sun Y, Liu S, Ferguson S, Wang L, Klepcyk P, Yun JS, Friedman JE (2002) Phosphoenolpyruvate carboxykinase overexpression selectively attenuates insulin signaling and hepatic insulin sensitivity in transgenic mice. J Biol Chem 277(26):23301–23307. doi:10.1074/jbc.M200964200 CrossRef Sun Y, Liu S, Ferguson S, Wang L, Klepcyk P, Yun JS, Friedman JE (2002) Phosphoenolpyruvate carboxykinase overexpression selectively attenuates insulin signaling and hepatic insulin sensitivity in transgenic mice. J Biol Chem 277(26):23301–23307. doi:10.​1074/​jbc.​M200964200 CrossRef
9.
go back to reference Mothers’ and Children’s Health and Welfare Association (2006) The main statistics of maternal and child health. Mothers’ and Children’s Health Organization Co. Ltd, Tokyo Mothers’ and Children’s Health and Welfare Association (2006) The main statistics of maternal and child health. Mothers’ and Children’s Health Organization Co. Ltd, Tokyo
10.
go back to reference Simmons RA, Templeton LJ, Gertz SJ (2001) Intrauterine growth retardation leads to the development of type 2 diabetes in the rat. Diabetes 50(10):2279–2286CrossRef Simmons RA, Templeton LJ, Gertz SJ (2001) Intrauterine growth retardation leads to the development of type 2 diabetes in the rat. Diabetes 50(10):2279–2286CrossRef
11.
go back to reference Vuguin P, Raab E, Liu B, Barzilai N, Simmons R (2004) Hepatic insulin resistance precedes the development of diabetes in a model of intrauterine growth retardation. Diabetes 53(10):2617–2622CrossRef Vuguin P, Raab E, Liu B, Barzilai N, Simmons R (2004) Hepatic insulin resistance precedes the development of diabetes in a model of intrauterine growth retardation. Diabetes 53(10):2617–2622CrossRef
13.
go back to reference Garg M, Thamotharan M, Dai Y, Thamotharan S, Shin BC, Stout D, Devaskar SU (2012) Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity. Diabetes 61(6):1391–1398. doi:10.2337/db11-1347 CrossRef Garg M, Thamotharan M, Dai Y, Thamotharan S, Shin BC, Stout D, Devaskar SU (2012) Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity. Diabetes 61(6):1391–1398. doi:10.​2337/​db11-1347 CrossRef
14.
go back to reference Henning SJ (1981) Postnatal development: coordination of feeding, digestion, and metabolism. Am J Physiol 241(3):G199–G214 Henning SJ (1981) Postnatal development: coordination of feeding, digestion, and metabolism. Am J Physiol 241(3):G199–G214
15.
go back to reference Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275
17.
go back to reference Garg M, Thamotharan M, Dai Y, Lagishetty V, Matveyenko AV, Lee WN, Devaskar SU (2013) Glucose intolerance and lipid metabolic adaptations in response to intrauterine and postnatal calorie restriction in male adult rats. Endocrinology 154(1):102–113. doi:10.1210/en.2012-1640 CrossRef Garg M, Thamotharan M, Dai Y, Lagishetty V, Matveyenko AV, Lee WN, Devaskar SU (2013) Glucose intolerance and lipid metabolic adaptations in response to intrauterine and postnatal calorie restriction in male adult rats. Endocrinology 154(1):102–113. doi:10.​1210/​en.​2012-1640 CrossRef
18.
go back to reference Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, Kahn CR (2000) Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 6(1):87–97CrossRef Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, Kahn CR (2000) Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 6(1):87–97CrossRef
20.
go back to reference Cassuto H, Kochan K, Chakravarty K, Cohen H, Blum B, Olswang Y, Hakimi P, Xu C, Massillon D, Hanson RW, Reshef L (2005) Glucocorticoids regulate transcription of the gene for phosphoenolpyruvate carboxykinase in the liver via an extended glucocorticoid regulatory unit. J Biol Chem 280(40):33873–33884. doi:10.1074/jbc.M504119200 CrossRef Cassuto H, Kochan K, Chakravarty K, Cohen H, Blum B, Olswang Y, Hakimi P, Xu C, Massillon D, Hanson RW, Reshef L (2005) Glucocorticoids regulate transcription of the gene for phosphoenolpyruvate carboxykinase in the liver via an extended glucocorticoid regulatory unit. J Biol Chem 280(40):33873–33884. doi:10.​1074/​jbc.​M504119200 CrossRef
21.
go back to reference Mutel E, Gautier-Stein A, Abdul-Wahed A, Amigo-Correig M, Zitoun C, Stefanutti A, Houberdon I, Tourette JA, Mithieux G, Rajas F (2011) Control of blood glucose in the absence of hepatic glucose production during prolonged fasting in mice: induction of renal and intestinal gluconeogenesis by glucagon. Diabetes 60(12):3121–3131. doi:10.2337/db11-0571 CrossRef Mutel E, Gautier-Stein A, Abdul-Wahed A, Amigo-Correig M, Zitoun C, Stefanutti A, Houberdon I, Tourette JA, Mithieux G, Rajas F (2011) Control of blood glucose in the absence of hepatic glucose production during prolonged fasting in mice: induction of renal and intestinal gluconeogenesis by glucagon. Diabetes 60(12):3121–3131. doi:10.​2337/​db11-0571 CrossRef
22.
go back to reference Baserga M, Hale MA, McKnight RA, Yu X, Callaway CW, Lane RH (2005) Uteroplacental insufficiency alters hepatic expression, phosphorylation, and activity of the glucocorticoid receptor in fetal IUGR rats. Am J Physiol Regul Integr Comp Physiol 289(5):R1348–R1353. doi:10.1152/ajpregu.00211.2005 CrossRef Baserga M, Hale MA, McKnight RA, Yu X, Callaway CW, Lane RH (2005) Uteroplacental insufficiency alters hepatic expression, phosphorylation, and activity of the glucocorticoid receptor in fetal IUGR rats. Am J Physiol Regul Integr Comp Physiol 289(5):R1348–R1353. doi:10.​1152/​ajpregu.​00211.​2005 CrossRef
23.
go back to reference Bertram C, Trowern AR, Copin N, Jackson AA, Whorwood CB (2001) The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11β-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142(7):2841–2853. doi:10.1210/endo.142.7.8238 Bertram C, Trowern AR, Copin N, Jackson AA, Whorwood CB (2001) The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11β-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142(7):2841–2853. doi:10.​1210/​endo.​142.​7.​8238
24.
go back to reference Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC (2005) Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 135(6):1382–1386 Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC (2005) Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 135(6):1382–1386
25.
go back to reference Lillycrop KA, Slater-Jefferies JL, Hanson MA, Godfrey KM, Jackson AA, Burdge GC (2007) Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br J Nutr 97(6):1064–1073. doi:10.1017/s000711450769196x CrossRef Lillycrop KA, Slater-Jefferies JL, Hanson MA, Godfrey KM, Jackson AA, Burdge GC (2007) Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br J Nutr 97(6):1064–1073. doi:10.​1017/​s000711450769196​x CrossRef
26.
go back to reference Drake AJ, McPherson RC, Godfrey KM, Cooper C, Lillycrop KA, Hanson MA, Meehan RR, Seckl JR, Reynolds RM (2012) An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and foetal growth. Clin Endocrinol 77(6):808–815. doi:10.1111/j.1365-2265.2012.04453.x CrossRef Drake AJ, McPherson RC, Godfrey KM, Cooper C, Lillycrop KA, Hanson MA, Meehan RR, Seckl JR, Reynolds RM (2012) An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and foetal growth. Clin Endocrinol 77(6):808–815. doi:10.​1111/​j.​1365-2265.​2012.​04453.​x CrossRef
27.
go back to reference Tenore A, Parks JS, Gasparo M, Koldovsky O (1980) Thyroidal response to peroral TSH in suckling and weaned rats. Am J Physiol 238(5):E428–E430 Tenore A, Parks JS, Gasparo M, Koldovsky O (1980) Thyroidal response to peroral TSH in suckling and weaned rats. Am J Physiol 238(5):E428–E430
Metadata
Title
Fasting for 3 days during the suckling–weaning transient period in male rats induces metabolic abnormalities in the liver and is associated with impaired glucose tolerance in adulthood
Authors
Misa Ikeda
Kazue Honma
Kazuki Mochizuki
Toshinao Goda
Publication date
01-04-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 3/2016
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-015-0919-9

Other articles of this Issue 3/2016

European Journal of Nutrition 3/2016 Go to the issue