Intrauterine diabetic milieu instigates dysregulated adipocytokines production in F1 offspring
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Background: Intrauterine environment plays a pivotal role in the origin of fatal diseases such as the metabolic syndrome. Diabetes is associated with low-grade inflammatory state and dysregulated adipokines production. The aim of this study is to investigate the effect of maternal diabetes on adipocytokines (adiponectin, leptin and TNF-α) production in F1 offspring in rats. Methods: The offspring groups were as follows: F1 offspring of control mothers under control diet (CD) (CF1-CD), F1 offspring of control mothers under high caloric diet (HCD) (CF1-HCD), F1 offspring of diabetic mothers under CD (DF1-CD), and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks post-natal, 10 pups of each subgroup were culled to obtain blood samples for biochemical analysis. Results: The results indicate that DF1-CD and DF1-HCD groups exhibited hyperinsulinemia, dyslipidemia, insulin resistance and impaired glucose homeostasis compared to CF1-CD (p > 0.05). DF1-CD and DF1-HCD groups had high hepatic and muscular depositions of TGs. The significant elevated NEFA level only appeared in offspring of diabetic mothers that was fed HCD. DF1-CD and DF1-HCD groups demonstrated low serum levels of adiponectin, high levels of leptin, and elevated levels of TNF-α compared to CF1-CD (p > 0.05). These results reveal the disturbed metabolic lipid profile of offspring of diabetic mothers and could guide further characterization of the mechanisms involved. Conclusion: Dysregulated adipocytokines production could be a possible mechanism for the transgenerational transmittance of diabetes, especially following a postnatal diabetogenic environment. Moreover, the exacerbating effects of postnatal HCD on NEFA in rats might be prone to adipcytokine dysregulation. Furthermore, dysregulation of serum adipokines is a prevalent consequence of maternal diabetes and could guide further investigations to predict the development of metabolic disturbances.
Abstract
Background: Intrauterine environment plays a pivotal role in the origin of fatal diseases such as the metabolic syndrome. Diabetes is associated with low-grade inflammatory state and dysregulated adipokines production. The aim of this study is to investigate the effect of maternal diabetes on adipocytokines (adiponectin, leptin and TNF-α) production in F1 offspring in rats. Methods: The offspring groups were as follows: F1 offspring of control mothers under control diet (CD) (CF1-CD), F1 offspring of control mothers under high caloric diet (HCD) (CF1-HCD), F1 offspring of diabetic mothers under CD (DF1-CD), and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks post-natal, 10 pups of each subgroup were culled to obtain blood samples for biochemical analysis. Results: The results indicate that DF1-CD and DF1-HCD groups exhibited hyperinsulinemia, dyslipidemia, insulin resistance and impaired glucose homeostasis compared to CF1-CD (p > 0.05). DF1-CD and DF1-HCD groups had high hepatic and muscular depositions of TGs. The significant elevated NEFA level only appeared in offspring of diabetic mothers that was fed HCD. DF1-CD and DF1-HCD groups demonstrated low serum levels of adiponectin, high levels of leptin, and elevated levels of TNF-α compared to CF1-CD (p > 0.05). These results reveal the disturbed metabolic lipid profile of offspring of diabetic mothers and could guide further characterization of the mechanisms involved. Conclusion: Dysregulated adipocytokines production could be a possible mechanism for the transgenerational transmittance of diabetes, especially following a postnatal diabetogenic environment. Moreover, the exacerbating effects of postnatal HCD on NEFA in rats might be prone to adipcytokine dysregulation. Furthermore, dysregulation of serum adipokines is a prevalent consequence of maternal diabetes and could guide further investigations to predict the development of metabolic disturbances.
참고문헌 (23)
- Gluckman PD, "The developmental origins of the metabolic syndrome", Trends Endocrinol Metab, 15(4), pp.183~187 (2004)
- Aerts L, "Animal evidence for the transgenerational development of diabetes mellitus", Int J Biochem Cell Biol, 38(5), pp.894~903 (2006)
- Fowden AL, "Intrauterine programming of physiological systems: causes and consequences", Physiology, 21(1), pp.29~37 (2006)
- Saad MI, "Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells", Endocrine, 50(537), pp.1~31 (2015)[DOI]
- Saad MI, "Modulation of adipocytokines production and serum NEFA level by metformin, glimepiride, and sitagliptin in HFD", STZ diabetic rats, 2015, ~
- Tawfik SH, "Similar and additive effects of ovariectomy and diabetes on insulin resistance and lipid metabolism", Biochem Res Int (2015)
- Zorena K, "Relationship between serum levels of tumor necrosis factor-alpha and interleukin-6 in diabetes mellitus type 1 children", Cen Eur J Immunol, 32(3), pp.124~ (2007)
- Makino N, "High serum TNF-α level in Type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells", J Diabetes Complicat, 19(6), pp.347~355 (2005)
- Liguori A, "Epigenetic changes predisposing to type 2 diabetes in intrauterine growth retardation", Front Endocrinol, 1 (2010)
- Reusens B, "Programming of the endocrine pancreas by the early nutritional environment", Int J Biochem Cell Biol, 38(5), pp.913~922 (2006)
- Kamel MA, "Prenatal effects of different intra-uterine milieus on fetal glucose sensing mechanisms during gestation in rats. 2012", Journal of Diabetes &Metabolism (2012)
- Kanaka‐Gantenbein C, "Fetal origins of adult diabetes", Ann N Y Acad Sci, 1205(1), pp.99~105 (2010)
- Mooradian AD, "Dyslipidemia in type 2 diabetes mellitus", Nat Clin Pract Endocrinol Metab, 5(3), pp.150~159 (2009)
- Delarue J, "Free fatty acids and insulin resistance", Curr Opin Clin Nutr Metab Care, 10(2), pp.142~148 (2007)
- Boden G, "Free fatty acids in obesity and type 2 diabetes:defining their role in the development of insulin resistance and β‐cell dysfunction", Eur J Clin Investig, 32(s3), pp.14~23 (2002)
- Steneberg P, "Hyperinsulinemia enhances hepatic expression of the fatty acid transporter Cd36 and provokes hepatosteatosis and hepatic insulin resistance", J Biol Chem, 290(31), pp.19034~19043 (2015)
- Morino K, "Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents", J Clin Investig, 115(12), pp.3587~ (2005)
- Hosokawa Y, "Clinical significance of serum adiponectin in Japanese diabetic patients", Diabetol Int, 2(2), pp.65~71 (2011)
- Ruotsalainen E, "Markers of endothelial dysfunction and low-grade inflammation are associated in the offspring of type 2 diabetic subjects", Atherosclerosis, 197(1), pp.271~277 (2008)
- Ruotsalainen E, "Changes in inflammatory cytokines are related to impaired glucose tolerance in offspring of type 2 diabetic subjects", Diabetes Care, 29(12), pp.2714~2720 (2006)
- Maltezos E, "Tumour necrosis factor-α levels in nondiabetic offspring of patients with type 2 diabetes mellitus", J Int Med Res, 30(6), pp.576~583 (2002)
- Dandona P, "Inflammation: the link between insulin resistance, obesity and diabetes", Trends Immunol, 25(1), pp.4~7 (2004)
- Yamakawa I, "Inactivation of TNF-α ameliorates diabetic neuropathy in mice", Am J Physiol-Endocrinol Metab, 301(5), pp.E844~E852 (2011)