Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice

被引:74
作者
Isganaitis, Elvira [1 ]
Woo, Melissa [1 ]
Ma, Huijuan [1 ]
Chen, Michael [1 ]
Kong, Wen [1 ]
Lytras, Aristides [1 ]
Sales, Vicencia [1 ]
DeCoste-Lopez, Jennifer [1 ]
Lee, Kyung-Ju [1 ]
Leatherwood, Cianna [1 ]
Lee, Deborah [1 ]
Fitzpatrick, Connor [1 ]
Gall, Walter [2 ]
Watkins, Steven [3 ]
Patti, Mary-Elizabeth [1 ]
机构
[1] Joslin Diabet Ctr, Div Integrat Physiol & Metab, Boston, MA 02215 USA
[2] Metabolon Inc, Res Triangle Pk, NC USA
[3] Lipomics Inc, West Sacramento, CA USA
基金
加拿大健康研究院;
关键词
HIGH-FAT DIET; WEIGHT-GAIN; URIC-ACID; OBESITY; PREGNANCY; ADIPONECTIN; ADIPOSITY; RECEPTOR; LEPTIN; SUBSTRATE;
D O I
10.2337/db13-0558
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice haploinsufficient for insulin receptor substrate-1 (IRS1-het) are hyperinsulinemic and insulin resistant during pregnancy, despite normal plasma glucose and body weight, and thus serve as a model of isolated maternal insulin resistance. Wild-type (WT) offspring of IRS1-het dams insulin resistance-exposed [IR-exposed] were compared with WT offspring of WT dams. Despite no differences in adiposity, male IR-exposed pups were glucose intolerant (P = 0.04) and hyperinsulinemic (1.3-fold increase, P = 0.02) by 1 month of age and developed progressive fasting hyperglycemia. Moreover, male IR-exposed pups challenged with high-fat diet exhibited insulin resistance. Liver lipidomic analysis of 3-week-old IR-exposed males revealed increases in the 16:1n7 fraction of several lipid classes, suggesting increased Scd1 activity. By 6 months of age, IR-exposed males had increased lipid accumulation in liver as well as increased plasma refed fatty acids, consistent with disrupted lipid metabolism. Our results indicate that isolated maternal insulin resistance, even in the absence of hyperglycemia or obesity, can promote metabolic perturbations in male offspring.
引用
收藏
页码:688 / 700
页数:13
相关论文
共 50 条
[41]   Olfactomedin 4 Deletion Improves Male Mouse Glucose Intolerance and Insulin Resistance Induced by a High-Fat Diet [J].
Li, Wenli ;
Aerbajinai, Wulin ;
Li, Hongzhen ;
Liu, Yueqin ;
Gavrilova, Oksana ;
Jain, Shalini ;
Rodgers, Griffin P. .
ENDOCRINOLOGY, 2018, 159 (09) :3235-3244
[42]   Chronic hyperinsulinemia contributes to insulin resistance under dietary restriction in association with altered lipid metabolism in Zucker diabetic fatty rats [J].
Morita, Ippei ;
Tanimoto, Keiichi ;
Akiyama, Nobuteru ;
Naya, Noriyuki ;
Fujieda, Kumiko ;
Iwasaki, Takanori ;
Yukioka, Hideo .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2017, 312 (04) :E237-E245
[43]   Maternal high-fat diet induces insulin resistance and deterioration of pancreatic β-cell function in adult offspring with sex differences in mice [J].
Yokomizo, Hisashi ;
Inoguchi, Toyoshi ;
Sonoda, Noriyuki ;
Sakaki, Yuka ;
Maeda, Yasutaka ;
Inoue, Tomoaki ;
Hirata, Eiichi ;
Takei, Ryoko ;
Ikeda, Noriko ;
Fujii, Masakazu ;
Fukuda, Kei ;
Sasaki, Hiroyuki ;
Takayanagi, Ryoichi .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2014, 306 (10) :E1163-E1175
[44]   5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice [J].
X. M. Song ;
M. Fiedler ;
D. Galuska ;
J. W. Ryder ;
M. Fernström ;
A. V. Chibalin ;
H. Wallberg-Henriksson ;
J. R. Zierath .
Diabetologia, 2002, 45 :56-65
[45]   5-aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice [J].
Song, XM ;
Fiedler, M ;
Galuska, D ;
Ryder, JW ;
Fernström, M ;
Chibalin, AV ;
Wallberg-Henriksson, H ;
Zierath, JR .
DIABETOLOGIA, 2002, 45 (01) :56-65
[46]   Melatonin Improves Glucose Homeostasis and Endothelial Vascular Function in High-Fat Diet-Fed Insulin-Resistant Mice [J].
Sartori, Claudio ;
Dessen, Pierre ;
Mathieu, Caroline ;
Monney, Anita ;
Bloch, Jonathan ;
Nicod, Pascal ;
Scherrer, Urs ;
Duplain, Herve .
ENDOCRINOLOGY, 2009, 150 (12) :5311-5317
[47]   Programming of central and peripheral insulin resistance by low birthweight and postnatal catch-up growth in male mice [J].
Berends, Lindsey M. ;
Dearden, Laura ;
Tung, Yi Chun L. ;
Voshol, Peter ;
Fernandez-Twinn, Denise S. ;
Ozanne, Susan E. .
DIABETOLOGIA, 2018, 61 (10) :2225-2234
[48]   Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice [J].
Jalabert, Audrey ;
Vial, Guillaume ;
Guay, Claudiane ;
Wiklander, Oscar P. B. ;
Nordin, Joel Z. ;
Aswad, Hala ;
Forterre, Alexis ;
Meugnier, Emmanuelle ;
Pesenti, Sandra ;
Regazzi, Romano ;
Danty-Berger, Emmanuelle ;
Ducreux, Sylvie ;
Vidal, Hubert ;
El-Andaloussi, Samir ;
Rieusset, Jennifer ;
Rome, Sophie .
DIABETOLOGIA, 2016, 59 (05) :1049-1058
[49]   Baicalin ameliorates insulin resistance and regulates hepatic glucose metabolism via activating insulin signaling pathway in obese pre-diabetic mice [J].
Miao, Lingchao ;
Zhang, Xutao ;
Zhang, Haolin ;
Cheong, Meng Sam ;
Chen, Xiaojia ;
Farag, Mohamed A. ;
San Cheang, Wai ;
Xiao, Jianbo .
PHYTOMEDICINE, 2024, 124
[50]   Preweaning Growth Hormone Treatment Ameliorates Adipose Tissue Insulin Resistance and Inflammation in Adult Male Offspring Following Maternal Undernutrition [J].
Reynolds, C. M. ;
Li, M. ;
Gray, C. ;
Vickers, M. H. .
ENDOCRINOLOGY, 2013, 154 (08) :2676-2686