Offspring Exercise Modulates Beige Adipocyte Numbers by Differential Regulation of H3K9 Methyltransferase G9a and Demethylase KDM4C in Mice Fed a Maternal High Fat Diet (P21-067-19)

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.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzz049.p19-003-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Kate Larson ◽

Amy Bundy ◽

Travis Alvine ◽

James Roemmich

Keyword(s):

Skeletal Muscle ◽

Agricultural Research ◽

Wheel Running ◽

Fetal Weight ◽

High Fat ◽

Placental Development ◽

Funding Sources ◽

Service Project ◽

Diet And Exercise ◽

Placental Inflammation

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.

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Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice

PLoS ONE ◽

10.1371/journal.pone.0130259 ◽

2015 ◽

Vol 10 (7) ◽

pp. e0130259 ◽

Cited By ~ 15

Author(s):

Thomas H. Reynolds ◽

Sayani Banerjee ◽

Vishva Mitra Sharma ◽

Jacob Donohue ◽

Sandrine Couldwell ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Wheel Running ◽

High Fat ◽

Voluntary Wheel Running ◽

Running Exercise ◽

Voluntary Wheel

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Maternal Vitamin a Supplementation Modulates Adipose Tissue Development in Offspring of Rats Consuming a High-Fat Diet (FS06-02-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz029.fs06-02-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Shu Hang Kwan ◽

Katelyn Senkus ◽

Kristi Crowe-White ◽

Libo Tan

Keyword(s):

Adipose Tissue ◽

Vitamin A ◽

High Fat Diet ◽

Sprague Dawley ◽

High Fat ◽

Serum Samples ◽

Metabolic Complications ◽

Funding Sources ◽

Sprague Dawley Rats ◽

Adipose Tissue Development

Abstract Objectives Vitamin A (VA) is a key regulator of obesity development and associated metabolic complications in adults. The aim of this study is to assess the impacts of VA supplementation during suckling and post-weaning periods on the adipose tissue (AT) development in rats reared by mothers consuming a high-fat diet (HFD). Methods Four Sprague-Dawley rats arrived on their 2nd day of gestation. After 3 days of acclimation, they were randomized to either a normal-fat diet (NFD = 25% fat) with adequate VA at 2.6 mg/kg (n = 2) or a HFD (50% fat) with the same amount of VA (n = 2). Upon delivery, pups were transferred to achieve a same number of n = 11/litter. Two mother rats, one from each group, were switched to a NFD and a HFD both with supplemented VA at 129 mg/kg (NFD + VA and HFD + VA), respectively. The other two remained on their diets with adequate VA through lactation (NFD and HFD). At postnatal day 14 (P14) and P25, 4 pups/litter were euthanized with body weight (BW), visceral white AT (WAT) mass, and brown AT (BAT) mass recorded. Serum samples from P25 necropsy were analyzed for glucose, lipids, leptin, adiponectin, and inflammatory biomarkers. At P25, the rest weanling pups (n = 3/group) were fed the diets as their respective mothers until they were euthanized at P35. Results At P14 and P25, the BW and WAT mass of pups in the HFD group were significantly (P < 0.05) higher than those in the NFD groups. Comparatively, these measures were significantly reduced in the HFD + VA group as compared to the HFD litter. A similar pattern of change in WAT mass was observed at P35. Additionally, at P25, the BAT mass of pups was significantly reduced by the maternal HFD, but VA supplement restored the level to that in the NFD groups. Serum analysis from P25 revealed a significantly higher adiponectin level in the HFD + VA group. In contrast, VA supplement showed a trend to reduce the glucose and leptin levels that were raised by the maternal HFD consumption. Conclusions Results support a regulatory role of VA supplementation during suckling and post-weaning period in the AT development in offspring from mothers consuming a HFD as evidenced by reduced BW and WAT mass, increased BAT mass, and modulation of adipokines. Future analysis will be conducted to study the mechanisms by which VA may impact the adipogenesis, WAT browning, and AT secretory functions. Funding Sources NIH.

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Exposure to maternal hyperglycemia and high-fat diet consumption after weaning in rats: repercussions on periovarian adipose tissue

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174421000672 ◽

2021 ◽

pp. 1-8

Author(s):

Carolina M. Saullo ◽

Yuri K. Sinzato ◽

Verônyca G. Paula ◽

Franciane Q. Gallego ◽

José E. Corrente ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Adult Life ◽

Maternal Diabetes ◽

Female Offspring ◽

Standard Diet ◽

High Fat ◽

Intrauterine Environment ◽

Tissue Samples ◽

Maternal Hyperglycemia

Abstract Clinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring.

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Long-term effects of a maternal high-fat: high-fructose diet on offspring growth and metabolism and impact of maternal taurine supplementation

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174419000709 ◽

2019 ◽

Vol 11 (4) ◽

pp. 419-426 ◽

Cited By ~ 1

Author(s):

M. Li ◽

C. M. Reynolds ◽

C. Gray ◽

R. Patel ◽

D. M. Sloboda ◽

...

Keyword(s):

Adipose Tissue ◽

Maternal Obesity ◽

Maternal Diet ◽

Control Diet ◽

Well Being ◽

Oral Glucose ◽

Long Term Effects ◽

High Fat ◽

Taurine Supplementation ◽

Maternal Undernutrition

AbstractObjective:Maternal obesity is associated with obesity and metabolic disorders in offspring. However, there remains a paucity of data on strategies to reverse the effects of maternal obesity on maternal and offspring health. With maternal undernutrition, taurine supplementation improves outcomes in offspring mediated in part via improved glucose–insulin homeostasis. The efficacy of taurine supplementation in the setting of maternal obesity on health and well-being of offspring is unknown. We examined the effects of taurine supplementation on outcomes related to growth and metabolism in offspring in a rat model of maternal obesity.Design:Wistar rats were randomised to: 1) control diet during pregnancy and lactation (CON); 2) CON with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (MO); or 4) MO with taurine (MOT). Offspring were weaned onto the control diet for the remainder of the study.Results:At day 150, offspring body weights and adipose tissue weights were increased in MO groups compared to CON. Adipose tissue weights were reduced in MOT versus MO males but not females. Plasma fasting leptin and insulin were increased in MO offspring groups but were not altered by maternal taurine supplementation. Plasma homocysteine concentrations were reduced in all maternal taurine-supplemented offspring groups. There were significant interactions across maternal diet, taurine supplementation and sex for response to an oral glucose tolerance test , a high-fat dietary preference test and pubertal onset in offspring.Conclusions:These results demonstrate that maternal taurine supplementation can partially ameliorate adverse developmental programming effects in offspring in a sex-specific manner.

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A long-term maternal diet transition from high-fat diet to normal fat diet during pre-pregnancy avoids adipose tissue inflammation in next generation

PLoS ONE ◽

10.1371/journal.pone.0209053 ◽

2018 ◽

Vol 13 (12) ◽

pp. e0209053 ◽

Cited By ~ 2

Author(s):

Michelle Summerfield ◽

Yi Zhou ◽

Tianhao Zhou ◽

Chaodong Wu ◽

Gianfranco Alpini ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Maternal Diet ◽

Adipose Tissue Inflammation ◽

Next Generation ◽

High Fat ◽

Tissue Inflammation

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Differential Effects of Lycopene Supplementation on Adipose Tissue Development and Redox Status in Weanling Offspring of Rats Consuming a High Fat Diet

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_103 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 470-470

Author(s):

Katelyn Senkus ◽

Yanqi Zhang ◽

Libo Tan ◽

Kristi Crowe-White

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Molecular Mechanisms ◽

Lipid Peroxides ◽

Redox Status ◽

Sprague Dawley ◽

High Fat ◽

Funding Sources ◽

Adipose Tissue Development ◽

Fat Diets

Abstract Objectives Dietary patterns high in fat contribute to the onset of cardiometabolic disease through accrual of adipose tissue (AT). Nevertheless, carotenoids, such as lycopene, may disrupt these metabolic perturbations. The purpose of this study was to evaluate AT development, systemic and AT redox status, and cardiometabolic biomarkers during weaning and post-weaning periods of offspring from mothers fed high fat diets with and without lycopene supplementation. Methods Sprague-Dawley rats arrived on the 2nd day of gestation and were randomized to 25% normal fat diet (NFD) or 50% high fat diet (HFD). Upon delivery, half of HFD mothers were transitioned to HFD supplemented with 1% lycopene (HFDL group). Remaining mothers continued NFD or HFD without supplementation. Four pups/litter were euthanized at postnatal day 25 (P25). Beginning at P25, weanling pups were fed diets of their respective mothers until euthanization at P35 (three pups/litter). Visceral white AT (WAT) and brown AT (BAT) mass was determined, as well as lipid peroxides and antioxidant capacity (AC) of these tissues and serum. Cardiometabolic biomarkers were assessed at P25. Results At each time point, HFD groups had significantly greater (P < 0.05) WAT accrual compared to NFD group, sufficiently representing diet-induced obesity. Compared to the HFD group, the HFDL group exhibited significantly greater BAT at P25 (P = 0.025) with a significant reduction in WAT mass (P = 0.004). Such patterns continued into P35, albeit non-significant. At both time points, serum lipid peroxides were significantly lower in the HFDL group compared to the HFD (P = 0.005, P = 0.003, respectively). In contrast, AT results were starkly different such that the HFDL group exhibited significantly greater (P < 0.05) lipid peroxides in WAT and BAT at P25 and P35 compared to HFD group. No significant differences in systemic or AT AC were observed between groups. Furthermore, serum adiponectin and leptin did not differ significantly between groups despite the aforementioned modifications in AT development. Conclusions Results from this exploratory analysis suggest that lycopene may induce favorable alterations in AT development, yet it differentially influences redox status in serum and AT. Additional research is warranted to elucidate molecular mechanisms by which lycopene influences AT biology and redox status. Funding Sources NIH.

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Adipose Tissue Development and Metabolic Profile of Neonatal and Weanling Sprague-Dawley Rats in Response to a Maternal High Fat Diet Supplemented with Lycopene (P08-050-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p08-050-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Katelyn Senkus ◽

Shu Hang Kwan ◽

Libo Tan ◽

Kristi Crowe-White

Keyword(s):

Adipose Tissue ◽

Adipocyte Differentiation ◽

Sprague Dawley ◽

High Fat ◽

Serum Samples ◽

Funding Sources ◽

Sprague Dawley Rats ◽

Adipose Tissue Development ◽

Fat Diets ◽

Glucose Dynamics

Abstract Objectives Excess adipose tissue (AT) may undergo adipocyte differentiation in response to nutritional stimuli. It is unknown if lycopene may metabolically activate adaptive thermogenesis and disrupt the ensuing dysfunction of an excessive energy burden. The purpose of this study was to assess AT development and metabolic profiles of Sprague-Dawley offspring from mothers fed high fat diets (HFD = 50% fat) supplemented with 1% lycopene during the suckling and post-weaning period. Methods Three Sprague-Dawley rats arrived on their 2nd day of gestation, and after three days of acclimation, mothers were randomized to a 25% normal-fat diet (NFD) or HFD. Upon delivery, one of the HFD mothers was transitioned to a HFD supplemented with 1% lycopene. Four pups/litter were euthanized at postnatal day 14 and 25 (P14 and P25, respectively) with body weight (BW) as well as the mass of visceral white AT (WAT) and brown AT (BAT) recorded. Serum samples from the P25 necropsy were analyzed for glucose, lipids, leptin, adiponectin, and inflammatory biomarkers. At P25, the remaining weanling pups (3 pups/litter) were fed the diets of their respective mothers until euthanizing at postnatal week 5 (P35). Results The HFD was effective in inducing weight gain as evidenced by increases in BW and WAT in the HFD group not receiving lycopene supplementation compared to pups from the NFD litter across all time points. At P14, WAT was 42.5% lower (P = 0.003) in rats reared by mothers consuming lycopene-supplemented HFD compared to the non-supplemented HFD group. At P25, significant decreases in WAT (P = 0.004, 25.6% lower) were also observed concomitantly with significant increases in BAT (P = 0.025, 40% increase) in rats reared by mothers consuming lycopene-supplemented HFD compared to the HFD group not receiving lycopene. Furthermore, at P25, glucose was 24% lower (P = 0.004) in the lycopene-supplemented HFD group. Albeit non-significant, BW and WAT in the lycopene-supplemented HFD group remained lower while BAT remained higher through P35. Conclusions Results suggest that lycopene may influence cardiometabolic outcomes such as accrual of AT mass and, subsequent obesity, as well as blood glucose dynamics. Additional research is warranted to determine diet-induced signaling pathways by which lycopene may influence adipocyte differentiation. Funding Sources NIH; University of Alabama Pilot Grant.

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