scholarly journals Paternal High Fat Diet and Exercise Differentially Regulate Placental Development and Inflammation in a Sex-Specific Manner in C57BL6/J Mice (P19-003-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kate Larson ◽  
Amy Bundy ◽  
Travis Alvine ◽  
James Roemmich

Abstract Objectives We have shown that increases in T2D risk in male offspring when the father consumes a high-fat (HF) diet can be normalized when the father also exercises during preconception, and that this protection may occur by epigenetic increases in insulin signaling within offspring skeletal muscle. In our current study, we investigated to determine how paternal HF diet and exercise conditions alter sperm miRNA, fetal weight and placental inflammation. Methods Three-week old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or a HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF diet fed dams. Sperm samples were collected to determine changes in miRNA that may account for the enhanced offspring skeletal muscle responses that helped normalize paternal HF-induced glucose intolerance. Placentae were collected to determine whether changes in sperm miRNA expression differed by amount of placental inflammation. Results Sperm expression of miRNA 193b increased with paternal HF and exercise. In F1 males, placental and fetal weight decreased with HF diet while, in F1 female, paternal HF and exercise had no effect on placental and fetal weights. Paternal HF diet decreased placental IL-6 and TNF-alpha mRNA expression in F1 females, while no effects were observed in F1 male placenta. Conclusions Taken together these data suggest that paternal HF diet has a greater impact on placental development of male fetuses while paternal exercise has greater impact on placental inflammation of female fetuses. For both female and male fetuses, these paternal influences are mediated via sperm miRNA 193b. miR-193b is involved in regulation of the cell cycle and adipogenesis but may have additional functions. Thus, the exact role of sperm miRNA 193b in sex-specific epigenetic transmission of paternal HF diet and exercise on placental and fetal development needs further evaluation. Funding Sources USDA Agricultural Research Service Project #3062-51000-052-00D.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kate Larson ◽  
Amy Bundy ◽  
Travis Alvine ◽  
Elizabeth Black Lance ◽  
James Roemmich

Abstract Objectives We have shown that a maternal low protein and postnatal high fat (HF) diet increases offspring obesity and type 2 diabetes mellitus (T2DM) risk by epigenetically reducing beige adipocyte (BA) numbers via increased protein expression of G9a (Histone3 Lysine9 dimethyl transferase), an inhibitor of the BA marker FGF21. It is not yet known whether offspring exercise reverses the offspring obesity and T2DM risk caused by the maternal HF diet. Methods Two month old female C57Bl/6 J mice (F0) were fed a normal fat (NF) 16% diet or a 45% HF diet for 3 months prior to breeding, and subsequent gestation and lactation. Male offspring (F1) were fed the same NF and HF diets and further divided into either cage active (CA) or voluntary wheel running (Ex) groups for an additional 3 months yielding eight groups: NF (maternal treatment condition)-Ex-NF (post weaning treatment conditions), NF-Ex-HF, NF-CA-NF, NF-CA-HF, HF-Ex-NF, HF-Ex-HF, HF-CA-NF, and HF-CA-HF. Subcutaneous adipose tissue samples were collected for protein and mRNA analysis of FGF21, G9a, E4BP4 (G9a coactivator), and H3K9 methylation regulators that are induced by exercise including Activating Transcription Factor 4 (ATF4) and H3K9 demethylases (KDM4C). Results Postnatal HF diet decreased FGF21 positive BA numbers regardless of the maternal diet. A postnatal HF diet plus limited postnatal activity (CA) increased G9a and E4BP4 expression to suppress FGF21, while a postnatal HF diet plus exercise condition increased KDM4C expression. Although BA were detectable, the morphology of BA under CA conditions were compromised or scarred. Conclusions These findings suggest that a postnatal HF diet has a greater impact on offspring adiposity and BA number than a maternal HF diet. These data also suggest that offspring exercise induces KDM4C to counter the increase in G9a triggered by a postnatal HF diet. Whether KDM4C induces reduction in H3K9-me2 to regulate adipose tissue FGF21 needs investigation. Futures studies should determine whether H3K9 epigenetic modifications in BA have any functional differences that contribute to the observed phenotypic abnormalities. Funding Sources USDA Agricultural Research Service Project #3062-51000-052-00D.


2017 ◽  
Vol 162 (1) ◽  
pp. 309-317 ◽  
Author(s):  
Jakob G Knudsen ◽  
Lærke Bertholdt ◽  
Anders Gudiksen ◽  
Sabine Gerbal-Chaloin ◽  
Martin Krøyer Rasmussen

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Anna Clarke ◽  
Nathan Horn ◽  
Gerald Shurson ◽  
Christopher Faulk ◽  
Lee Johnston

Abstract Objectives The objective of this study was to determine if supplementing mouse dam diets with β-hydroxy-β-methylbutyrate (HMB) calcium salt throughout gestation would improve pup fetal weight uniformity and placental development. Methods Data were collected from 27 genetically identical mouse dams and their offspring. Dams were assigned to one of 4 dietary treatments: Control (CON; n = 7), Low HMB (LHMB; 3.5 mg/g diet; n = 6), High HMB (HHMB; 35 mg/g diet; n = 7), and low HMB pulse dose (PUL; 3.5 mg/g diet; n = 7) from days 6 to 10 of gestation. All dams were fed a swine lactation derived corn-soy diet with HMB supplementation only during gestation. Dams were euthanized on day 18 of gestation. Results Dietary treatment did not affect total number of pups per litter, but fetal weight was greater (P < 0.05) for pups from PUL dams (1.05 ± 0.02 g) than LHMB (0.94 ± 0.02 g) or HHMB (0.95 ± 0.02 g) dams. Within-litter variation (standard deviation and coefficient of variation) and range of fetal weights was not different among treatments. Differences between the median fetal weight within litter and weight of the lowest weight fetal pup in each litter were similar among treatments. Supplementation with HMB did not influence weight of placentae or area of the placental labyrinth. Placental efficiency, measured as fetal weight/placental weight, was less (P < 0.05) for LHMB dams compared to CON dams. Conclusions In conclusion, dietary supplementation of HMB for pregnant mice had no effect on fetal weight variation within litter. Supplementing diets with β-hydroxy-β-methylbutyrate had no effect on placental weight or labyrinth area but reduced placental efficiency in dams fed LHMB. Funding Sources This research has been supported and funded by BioMatrix International, Princeton, MN.


2015 ◽  
Vol 118 (11) ◽  
pp. 1331-1343 ◽  
Author(s):  
Jacqueline L. Beaudry ◽  
Emily C. Dunford ◽  
Erwan Leclair ◽  
Erin R. Mandel ◽  
Ashley J. Peckett ◽  
...  

Diabetes is rapidly induced in young male Sprague-Dawley rats following treatment with exogenous corticosterone (CORT) and a high-fat diet (HFD). Regular exercise alleviates insulin insensitivity and improves pancreatic β-cell function in insulin-resistant/diabetic rodents, but its effect in an animal model of elevated glucocorticoids is unknown. We examined the effect of voluntary exercise (EX) on diabetes development in CORT-HFD-treated male Sprague-Dawley rats (∼6 wk old). Animals were acclimatized to running wheels for 2 wk, then given a HFD, either wax (placebo) or CORT pellets, and split into 4 groups: placebo-sedentary (SED) or -EX and CORT-SED or -EX. After 2 wk of running combined with treatment, CORT-EX animals had reduced visceral adiposity, and increased skeletal muscle type IIb/x fiber area, oxidative capacity, capillary-to-fiber ratio and insulin sensitivity compared with CORT-SED animals (all P < 0.05). Although CORT-EX animals still had fasting hyperglycemia, these values were significantly improved compared with CORT-SED animals (14.3 ± 1.6 vs. 18.8 ± 0.9 mM). In addition, acute in vivo insulin response to an oral glucose challenge was enhanced ∼2-fold in CORT-EX vs. CORT-SED ( P < 0.05) which was further demonstrated ex vivo in isolated islets. We conclude that voluntary wheel running in rats improves, but does not fully normalize, the metabolic profile and skeletal muscle composition of animals administered CORT and HFD.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kate Larson ◽  
Danielle Krout ◽  
Travis Alvine ◽  
Huawei Zeng ◽  
Amy Bundy ◽  
...  

Abstract Objectives Maternal high-fat (HF) diet predisposes offspring to metabolic syndrome, in part, by inducing alterations during placental development resulting in abnormal fetal development and offspring birth weight. We previously reported in a rat model that a maternal malnutrition diet increases fetal inflammation, and placental vascularization, and decreases offspring birth weight followed by adult-onset obesity. In the current study, we investigated when during gestational development a maternal HF diet induces changes in placental weight, lipid content, and inflammation. We further investigated whether probiotic supplementation offsets HF-diet induced adverse outcomes. Methods Two-month old female C57BL/6 mice were fed diets of 16% fat (normal-fat, NF) or 45% fat (high-fat, HF) for 8 weeks followed by 4 weeks of probiotic (Bifidobacterium animalis subsp. lactis, BB-12) supplementation. Fetuses and placentae were examined mid- (D12) and late- (D19) gestation Results Placental length, width, and weight as well as fetal weight were decreased in the HF group at D12. Probiotic supplementation reversed the HF diet-induced reduction in placental weight at D12. These beneficial effects of probiotic supplementation were absent at D19 as fetal weights from all HF diet fed groups weighed less regardless of probiotic supplementation. Probiotic supplementation reduced placental TNF-alpha mRNA at D12 and IL-10 mRNA at D19. Triacylglyceride concentration was increased at D19 by HF diet, in part, by the preceding increases in lipoprotein lipase (LPL) and plasma membrane-associated fatty-acid binding protein (FABPpm) mRNA expression at D12. Conclusions These findings suggest that maternal HF diet alters placental size and weight as well as fetal weight and that probiotic supplementation renders a protective effect against these changes in mid-gestation. Future studies are needed to determine whether the protective mechanism of probiotic supplementation in mid-gestation has beneficial effects on offspring developmental programming. Funding Sources USDA Agricultural Research Service Project #3062-51000-052-00D.


2016 ◽  
Vol 4 (9) ◽  
pp. e12788 ◽  
Author(s):  
Jakob G. Knudsen ◽  
Ella Joensen ◽  
Laerke Bertholdt ◽  
Henrik Jessen ◽  
Line van Hauen ◽  
...  

2014 ◽  
Vol 117 (8) ◽  
pp. 869-879 ◽  
Author(s):  
Marcia J. Abbott ◽  
Lorraine P. Turcotte

AMP-activated protein kinase (AMPK) has been studied extensively and postulated to be a target for the treatment and/or prevention of metabolic disorders such as insulin resistance. Exercise training has been deemed a beneficial treatment for obesity and insulin resistance. Furthermore, exercise is a feasible method to combat high-fat diet (HFD)-induced alterations in insulin sensitivity. The purpose of this study was to determine whether AMPK-α2 activity is required to gain beneficial effects of exercise training with high-fat feeding. Wild-type (WT) and AMPK-α2 dominant-negative (DN) male mice were fed standard diet (SD), underwent voluntary wheel running (TR), fed HFD, or trained with HFD (TR + HFD). By week 6, TR, irrespective of genotype, decreased blood glucose and increased citrate synthase activity in both diet groups and decreased insulin levels in HFD groups. Hindlimb perfusions were performed, and, in WT mice with SD, TR increased insulin-mediated palmitate uptake (76.7%) and oxidation (>2-fold). These training-induced changes were not observed in the DN mice. With HFD, TR decreased palmitate oxidation (61–64%) in both WT and DN and increased palmitate uptake (112%) in the WT with no effects on palmitate uptake in the DN. With SD, TR increased ERK1/2 and JNK1/2 phosphorylation, regardless of genotype. With HFD, TR reduced JNK1/2 phosphorylation, regardless of genotype, carnitine palmitoyltransferase 1 expression in WT, and CD36 expression in both DN and WT. These data suggest that low AMPK-α2 signaling disrupts, in part, the exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following HFD.


Author(s):  
Katsuyuki Tokinoya ◽  
Seiko Ono ◽  
Kai Aoki ◽  
Koki Yanazawa ◽  
Yasuhiro Shishikura ◽  
...  

AbstractIntroductionExercise training is beneficial for reducing obesity. In particular, exercise training can lower the catecholamine concentration in circulation. Renalase, whose expression was first confirmed in the kidneys, is a physiologically active substance that decomposes circulating catecholamines; additionally, it has been reported to be present in the skeletal muscles. The aim of this study was to clarify the expression of renalase in the skeletal muscles and kidneys after high-intensity exercise training in obese mice.Material and methodsThe mice were divided into four groups: normal diet and sedentary, normal diet and exercise training, high-fat diet and sedentary, and high-fat diet and exercise training, and the test was performed for 8 weeks.ResultsBody weight and skeletal muscle wet weight were reduced by high-fat diet intake but were rescued by training. Skeletal muscle renalase gene expression was significantly increased by exercise training. However, in the kidneys the gene expression of renalase was significantly increased by high-fat diet intake and exercise training. No significant changes were observed in the gene expression of catecholamine-degrading enzymes, catechol-O-methyltransferase and monoamine oxidase A and B.ConclusionWe demonstrated that exercise training increased the gene expression of renalase in the skeletal muscles and kidneys, thus lowering circulating catecholamine levels. This may lead to amelioration of obesity as catecholamines are lipolytic.


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