Skip to main content Accessibility help

A post-weaning fish oil dietary intervention reverses adverse metabolic outcomes and 11β-hydroxysteroid dehydrogenase type 1 expression in postnatal overfed rats

  • Yanyan Dai (a1), Fan Yang (a1), Nan Zhou (a1), Lijun Sha (a1), Shanshan Zhou (a1), Junle Wang (a2) and Xiaonan Li (a1) (a3)...


Early life is considered a critical period for determining long-term metabolic health. Postnatal over-nutrition may alter glucocorticoid (GC) metabolism and increase the risk of developing obesity and metabolic disorders in adulthood. Our aim was to assess the effects of the dose and timing of a fish oil diet on obesity and the expression of GC-activated enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD1) in postnatal overfed rats. Litter sizes were adjusted to three (small litter (SL)) or ten (normal litter) rats on postnatal day 3 to induce overfeeding or normal feeding. The SL rats were divided into three groups after weaning: high-dose fish oil (HFO), low-dose fish oil (LFO) and standard-diet groups. After 10 weeks, the HFO diet reduced body weight gain (16 %, P<0·05), improved glucose intolerance and decreased hyperlipaemia levels (P<0·05) in SL rats, but the LFO diet did not have any effect on the same rats. Moreover, we chose postnatal week 3 (W3), 6 (W6) and 8 (W8) as the intervention time points at which to begin the 10-week HFO diet, and found that the HFO diet improved glucose utilisation and lipid metabolism at all time points. However, body weight of SL rats was reversed to normal levels by the post-weaning intervention (461 (sem 9·1) v. 450 (sem 2·0)). 11β-HSD1 mRNA expression in the adipose tissue (49 (sem 7·5) v. 161 (sem 18·3), P<0·05) and hepatic tissue (11 (sem 0·9) v. 16 (sem 1·5), P<0·05) was decreased by the HFO diet at W3, but not at W6 or W8 (P>0·05). In conclusion, the post-weaning HFO diet could reverse adverse outcomes and decrease tissue GC activity in postnatal overfed rats.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      A post-weaning fish oil dietary intervention reverses adverse metabolic outcomes and 11β-hydroxysteroid dehydrogenase type 1 expression in postnatal overfed rats
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      A post-weaning fish oil dietary intervention reverses adverse metabolic outcomes and 11β-hydroxysteroid dehydrogenase type 1 expression in postnatal overfed rats
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      A post-weaning fish oil dietary intervention reverses adverse metabolic outcomes and 11β-hydroxysteroid dehydrogenase type 1 expression in postnatal overfed rats
      Available formats


Corresponding author

* Corresponding author: X. Li, email


Hide All
1. Haidar, YM & Cosman, BC (2011) Obesity epidemiology. Clin Colon Rectal Surg 24, 205210.
2. Jing, L, Binkley, CM, Suever, JD, et al. (2016) Cardiac remodeling and dysfunction in childhood obesity: a cardiovascular magnetic responance study. J Cardiovasc Magn Reson 18, 28.
3. Ojha, S, Saroha, V, Symonds, ME, et al. (2013) Excess nutrient supply in early life and its later metabolic consequences. Clin Exp Pharmacol Physiol 40, 817823.
4. Koletzko, B, Symonds, ME & Olsen, SF (2011) Programming research: where are we and where do we go from here? Am J Clin Nutr 94, 6 Suppl, 2036s2043s.
5. Buckley, AJ, Jaquiery, AL & Harding, JE (2005) Nutritional programming of adult disease. Cell Tissue Res 322, 7379.
6. Armitage, JA, Khan, IY, Taylor, PD, et al. (2004) Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol 561, Pt 2, 355377.
7. Mostyn, A & Symonds, ME (2009) Early programming of adipose tissue function: a large-animal perspective. Proc Nutr Soc 68, 393400.
8. Habbout, A, Li, A, Rochette, L, et al. (2013) Postnatal overfeeding in rodents by litter size reduction induced major short- and long-term pathophysiological consequences. J Nutr 143, 553562.
9. Peckett, AJ, Wrigh, DC & Riddell, MC (2011) The effects of glucocorticoids on adipose tissue lipid metabolism. Metabolism 60, 15001510.
10. Gathercole, LL, Morgan, SA, Bujalska, IJ, et al. (2011) Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue. PLoS ONE 6, e26223.
11. Lee, MJ, Pramyothin, P, Karastergiou, K, et al. (2014) Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity. Biochim Biophys Acta 1842, 473481.
12. Bujalska, IJ, Kumar, S & Stewart, PM (1997) Does central obesity reflect ‘Cushing’s disease of the omentum’? Lancet 349, 12101213.
13. Stomby, A, Andrew, R, Walker, BR, et al. (2014) Tissue-specific dysregulation of cortisol regeneration by 11betaHSD1 in obesity: has it promised too much? Diabetologia 57, 11001110.
14. Masuzaki, H, Paterson, J, Shinyama, H, et al. (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294, 21662170.
15. Masuzaki, H, Yamamoto, H, Kenyon, CJ, et al. (2003) Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. J Clin Invest 112, 8390.
16. Johansson, A, Andrew, R, Forsberg, H, et al. (2001) Glucocorticoid metabolism and adrenocortical reactivity to ACTH in myotonic dystrophy. J Clin Endocrinol Metab 86, 42764283.
17. Dube, S, Norby, BJ, Pattan, V, et al. (2015) 11β-Hydroxysteroid dehydrogenase types 1 and 2 activity in subcutaneous adipose tissue in humans: implications in obesity and diabetes. J Clin Endocrinol Metab 100, E70E76.
18. Chapagain, A, Caton, PW, Kieswich, J, et al. (2014) Elevated hepatic 11β-hydroxysteroid dehydrogenase type 1 induces insulin resistance in uremia. Proc Natl Acad Sci U S A 111, 38173822.
19. Hou, M, Liu, Y, Zhu, L, et al. (2011) Neonatal overfeeding induced by small litter rearing causes altered glucocorticoid metabolism in rats. PLoS ONE 6, e25726.
20. Seckl, JR & Walker, BR (2004) 11beta-hydroxysteroid dehydrogenase type 1 as a modulator of glucocorticoid action: from metabolis to memeory. Trends Endocrinol Metab 15, 418424.
21. Harno, E, Cottrell, EC, Keevil, BG, et al. (2013) 11-Dehydrocorticosterone causes metabolic syndrome, which is prevented when 11β-HSD1 is knocked out in livers of male mice. Endocrinology 154, 35993609.
22. Poudyal, H, Panchal, SK, Diwan, V, et al. (2011) Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action. Prog Lipid Res 50, 372387.
23. Rafiee, M, Sotoideh, G, Djalali, M, et al. (2016) Dietary ω-3 polyunsaturated fatty acid intake modulates impact of insertion/deletion polymorphism of ApoB gene on obesity risk in type 2 diabetic patients. Nutrition 32, 11101115.
24. Simopoilos, AP (2000) Human reguirement for n-3 polyunsaturated fatty acids. Poilt Sci 79, 961970.
25. Patterson, E, Wall, R, Fitzgerald, GF, et al. (2012) Health implications of high dietary omega-6 polyunsaturated fatty acids. J Nutr Metab 2012, 539426.
26. Ailhaud, G, Massiera, F, Weill, P, et al. (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, 203236.
27. Buettner, R, Parhofer, KG, Woenckhaus, M, et al. (2006) Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J Mol Endocrinol 36, 485501.
28. Weitz, D, Weintraub, H, Fisher, E, et al. (2010) Fish oil for the treatment of cardiovascular disease. Cardiol Rev 18, 258263.
29. Nobili, V, Bedogni, G, Alisi, A, et al. (2011) Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial. Arch Dis Child 96, 350353.
30. Samane, S, Christon, R, Dombrowski, L, et al. (2009) Fish oil and argan oil intake differently modulate insulin resistance and glucose intolerance in a rat model of dietary-induced obesity. Metabolism 58, 909919.
31. Jelenik, T, Rossmeisl, M, Kuda, O, et al. (2010) AMP-activated protein kinase alpha2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids. Diabetes 59, 27372746.
32. Su, HY, Lee, HC, Cheng, WY, et al. (2015) A calorie-restriction diet supplemented with fish oil and high-protein powder is associated with reduced severity of metabolic syndrome in obese women. Eur J Clin Nutr 69, 322328.
33. Martínez-Fernández, L, Laiglesia, LM, Huerta, AE, et al. (2015) Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome. Prostaglandins Other Lipid Mediat 121, Pt A, 2441.
34. Hou, M, Ji, C, Wang, J, et al. (2009) The effects of dietary fatty acid composition in the post-sucking period on metabolic alterations in adulthood: can ω3 polyunsaturated fatty acids prevent adverse programming outcomes? J Endocrinol 215, 119127.
35. Stimson, RH & Walker, BR (2103) The role and regulation of 11β-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome. Horm Mol Biol Clin Investig 15, 3748.
36. Budge, H, Sebert, S, Sharkey, D, et al. (2009) Session on ‘obesity’. Adipose tissue development, nutrition in early life and its impact on later obesity. Proc Nutr Soc 68, 321326.
37. Symonds, ME, Pope, M, Sharkey, D, et al. (2012) Adipose tissue and fetal programming. Diabetologia 55, 15971606.
38. Ailhaud, G & Guesnet, P (2004) Fatty acid composition of fats is an early determinant of childhood obesity: a short review and an opinion. Obes Rev 5, 2126.
39. Lloyd, LJ, Langley-Evans, SC & McMullen, S (2010) Childhood obesity and adult cardiovascular disease risk: a systematic review. Int J Obes (Lond) 34, 1828.
40. Whitlock, EP, O’Connor, EA, Williams, SB, et al. (2010) Effectiveness of weight management interventions in children: a targeted systematic review for the USPSTF. Pediatrics 125, e396e418.
41. VanDevanter, DR, Kahle, JS, O’Sullivan, AK, et al. (2015) Cystic fibrosis in young children: a review of disease manifestation, progression, and response to early treatment. J Cyst Fibros 15, 147157.
42. von Berg, A, Filipiak-Pittroff, B, Schulz, H, et al. (2016) Allergic manifestation 15 years after early intervention with hydrolyzed formulas – the GINI study. Allergy 71, 210219.
43. Khan, A, McCormack, HC, Bolger, EA, et al. (2015) Childhood maltreatment, depression, and suicidal ideation: critical importance of parental and peer emotional abuse during developmental sensitive periods in males and females. Front Psychiatry 6, 42.
44. Plagemann, A, Harder, T, Schellong, K, et al. (2012) Early postnatal life as a critical time window for determination of long-term metabolic health. Best Pract Res Clin Endocrinol Metab 26, 641653.
45. Tirelli, E, Laviola, G & Adriani, W (2003) Ontogenesis of behavioral sensitization and conditioned place preference induced by psychostimulants in laboratory rodents. Neurosci Biobehav Rev 27, 163178.
46. Chen, H, Simar, D, Lambert, K, et al. (2008) Maternal and postnatal overnutrition differentially impact appetite regulators and fuel metabolism. Endocrinology 149, 53485356.
47. Bligh, EG & Dyer, WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37, 911917.
48. Patel, MS & Srinivasan, M (2011) Metabolic programming in the immediate postnatal life. Ann Nutr Metab 58, 1828.
49. Kremmyda, LS, Tvrzicka, E, Stankova, B, et al. (2011) Fatty acids as biocompounds: their role in human metabolism, health and disease: a review. Part 2: fatty acid physiological roles and applications in human health and disease. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 155, 195218.
50. Flachs, P, Horakova, O, Brauner, P, et al. (2005) Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia 48, 23652375.
51. Russo, GL (2009) Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol 77, 937946.
52. Simopoulos, AP (2006) Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 60, 502507.
53. Liu, HQ, Qiu, Y, Mu, Y, et al. (2013) A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats. Nutr Res 33, 849858.
54. Bertrand, C, Pignalosa, A, Wanecq, E, et al. (2013) Effects of dietary eicosapentaenoic acid (EPA) supplementation in high-fat fed mice on lipid metabolism and apelin/APJ system in skeletal muscle. PLOS ONE 8, e78874.
55. Pereira, SL, Leonard, AE, Huang, YS, et al. (2004) Identification of two novel microalgal enzymes involved in the conversion of the omega3-fatty acid, eicosapentaenoic acid, into docosahexaenoic acid. Biochem J 384, Pt 2, 357366.
56. Flachs, P, Rossmeisl, M & Kopecky, J (2014) The effect of n-3 fatty acids on glucose homeostasis and insulin sensitivity. Physiol Res 63, Suppl 1, S93S118.
57. Manickam, E, Sinclair, AJ & Cameron-Smith, D (2010) Suppressive actions of eicosapentaenoic acid on lipid droplet formation in 3T3-L1 adipocytes. Lipids Health Dis 9, 57.
58. Siriwardhana, N, Kalupahana, NS, Fletcher, S, et al. (2012) n-3 and n-6 polyunsaturated fatty acids differentially regulate adipose angiotensinogen and other inflammatory adipokines in part via NF-kappaB-dependent mechanisms. J Nutr Biochem 23, 16611667.
59. Victora, CG, Adair, L, Fall, C, et al. (2008) Maternal and child undernutrition: consequences for adult health and human capital. Lancet 371, 340357.
60. Gluckman, PD, Hanson, MA, Cooper, C, et al. (2008) Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 359, 6173.
61. Gallou-Kabani, C, Vigé, A, Gross, MS, et al. (2007) Resistance to high-fat diet in the female progeny of obese mice fed a control diet during the periconceptual, gestation, and lactation periods. Am J Physiol Endocrinol Metab 292, 10951100.
62. Chicco, A, Creus, A, lllesca, P, et al. (2016) Effect of post-suckling n-3 polyunsaturated fatty acids: prevention of dyslipidemia and liver steatosis induced in rats by a sucrose-rich diet during pre- and post-natal life. Food Funct 7, 445454.
63. Spalding, KL, Arner, E, Westermark, PO, et al. (2008) Dynamics of fat cell turnover in humans. Nature 453, 783787.
64. Bujalska, IJ, Kumar, S, Hewison, M, et al. (1999) Differentiation of adipose stromal cells: the roles of glucocorticoids and 11beta-hydroxysteroid dehydrogenase. Endocrinology 140, 31883196.
65. Shively, CA, Register, TC & Clarkson, TB (2009) Social stress, visceral obesity, and coronary artery atherosclerosis: product of a primate adaptation. Am J Primatol 71, 742751.
66. Tomlinson, JW & Stewart, PM (2007) Modulation of glucocorticoid action and the treatment of type-2 diabetes. Best Pract Res Clin Endocrinol Metab 21, 607619.
67. Chapman, K, Holmes, M & Seckl, J (2013) 11beta-Hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol Rev 93, 11391206.
68. Sun, J, Wang, Y, Li, Y, et al. (2014) Downregulation of PPARγ by miR-548d-5p suppresses the adipogenic differentiation of human bone marrow mesenchymal stem cells and enhances their osteogenic potential. J Transl Med 12, 168.
69. Hollenberg, AN, Susulic, VS, Madura, JP, et al. (1997) Functional antagonism between CCAAT/enhancer binding protein-alpha and peroxisome proliferator-activated receptor-gamma on the leptin promoter. J Biol Chem 272, 52835290.
70. Bruley, C, Lyons, V, Worsley, AG, et al. (2006) A novel promoter for the 11beta-hydroxysteroid dehydrogenase type 1 gene is active in lung and is C/EBPalpha independent. Endocrinology 147, 28792885.
71. Berger, J, Tanen, M, Elbrecht, A, et al. (2001) Peroxisome proliferator -activated receptor-gamma ligands inhibit adipocyte 11beta -hydroxysteroid dehydrogenase type 1 expression and activity. J Biol Chem 276, 1262912635.
72. Vagnerová, K, Loukotová, J, Ergang, P, et al. (2011) Peroxisome proliferator-activated receptor-γ stimulates 11β-hydroxysteroid dehydrogenase type 1 in rat vascular smooth muscle cells. Steroids 76, 577581.
73. Dube, S, Norby, B, Pattan, V, et al. (2014) Hepatic 11beta-hydroxysteroid dehydrogenase type 1 activity in obesity and type 2 diabetes using a novel triple tracer cortisol technique. Diabetologia 57, 14461455.
74. Paterson, JM, Morton, NM, Fievet, C, et al. (2004) Metabolic syndrome without obesity: hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. Proc Natl Acad Sci U S A 101, 70887093.
75. Harno, E, Cottrell, EC, Keevil, BG, et al. (2013) 11-Dehydrocorticosterone causes metabolic syndrome, which is prevented when 11beta-HSD1 is knocked out in livers of male mice. Endocrinology 154, 35993609.
76. Park, JS, Rhee, SD, Jung, WH, et al. (2012) Anti-diabetic and anti-adipogenic effects of a novel selective 11beta-hydroxysteroid dehydrogenase type 1 inhibitor in the diet-induced obese mice. Eur J Pharmacol 691, 1927.
77. Williams, LJ, Lyons, V, MacLeod, I, et al. (2000) C/EBP regulates hepatic transcription of 11beta-hydroxysteroid dehydrogenase type 1. A novel mechanism for cross-talk between the C/EBP and glucocorticoid signaling pathways. J Biol Chem 275, 3023230239.



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed