scholarly journals Hyperleptinemia During Pregnancy Decreases Adult Weight of Offspring and Is Associated With Increased Offspring Locomotor Activity in Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3777-3790 ◽  
Author(s):  
Kelly E. Pollock ◽  
Damaiyah Stevens ◽  
Kathleen A. Pennington ◽  
Rose Thaisrivongs ◽  
Jennifer Kaiser ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Food Consumption ◽  
Leptin Receptor ◽  
Female Offspring ◽  
Behavioral Changes ◽  
Wild Type ◽  
High Fat ◽  
Adult Weight ◽  
Total Food ◽  
Increased Risk

Pregnant women who are obese or have gestational diabetes mellitus have elevated leptin levels and their children have an increased risk for child and adult obesity. The goals of this study were to determine whether offspring weights are altered by maternal hyperleptinemia, and whether this occurs via behavioral changes that influence energy balance. We used 2 hyperleptinemic mouse models. The first was females heterozygous for a leptin receptor mutation (DB/+), which were severely hyperleptinemic, and that were compared with wild-type females. The second model was wild-type females infused with leptin (LEP), which were moderately hyperleptinemic, and were compared with wild-type females infused with saline (SAL). Total food consumption, food preference, locomotor activity, coordinated motor skills, and anxiety-like behaviors were assessed in wild-type offspring from each maternal group at 3 postnatal ages: 4–6, 11–13, and 19–21 weeks. Half the offspring from each group were then placed on a high-fat diet, and behaviors were reassessed. Adult offspring from both groups of hyperleptinemic dams weighed less than their respective controls beginning at 23 weeks of age, independent of diet or sex. Weight differences were not explained by food consumption or preference, because female offspring from hyperleptinemic dams tended to consume more food and had reduced preference for palatable, high-fat and sugar, food compared with controls. Offspring from DB/+ dams were more active than offspring of controls, as were female offspring of LEP dams. Maternal hyperleptinemia during pregnancy did not predispose offspring to obesity, and in fact, reduced weight gain.

Abstract 1129: Obesity-related Elevations in Soluble P-selectin are Derived From Endothelium and Dependent on Expression of Leukocyte P-selectin Glycoprotein Ligand-1

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Kevin J Wickenheiser ◽  
Peter F Bodary ◽  
Kristina Bahrou ◽  
Daniel T Eitzman
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Leptin Receptor ◽  
The Body ◽  
Wild Type ◽  
Post Transplant ◽  
Time Period ◽  
Increased Risk ◽  
Soluble P ◽  
Deficient Mice

Background : Obesity is associated with proinflammatory changes and an increased risk for vascular disease complications. The tissue source and mechanism by which soluble P-selectin (sPsel) is generated in obesity are unclear. Methods and Results : Soluble p-selectin (sPsel) levels were measured in the circulation from lean wild type and obese leptin receptor deficient mice (LepR−/−) at 4 and 10 weeks of age. In wild-type mice body weight increases from 13+/−2 to 20+/−3 grams over this time period while the body weight increases from 15+/−2 to 38+/−5 grams in LepR−/− mice. At 4 weeks of age sPsel levels were 103+/−8mg/mL in wild-type mice vs. 138+/−9 ng/mL in LepR−/− mice, p=0.048. By 10 wks of age sPsel increased to 112 +/− 2 in wild-type mice and 182 +/− 9 in LepR−/− mice, p=0.00005. In order to determine if the obesity-induced rise in sPsel is regulated by leukocyte Psgl-1, bone marrow transplantation was performed from Psgl+/+ or Psgl−/− donors into irradiated LepR−/−recipients. At 4 weeks post-transplant, sPsel levels were 166 +/−6 ng/mL in LepR−/− mice receiving Psgl+/+ marrow and 45 +/− 4 ng/mL in LepR−/− mice receiving Psgl−/− marrow, p=0.0000004. In order to determine if the sPsel in LepR−/− mice originated from the endothelium versus platelets, we transplanted Psel−/− bone marrow into irradiated LepR−/−mice. At 4 weeks post transplant, sPsel levels were 153 +/−3 ng/mL in LepR−/− mice receiving Psel−/− bone marrow and were not significantly different from LepR−/− mice receiving Psel+/+ bone marrow (166 +/−6 ng/mL, p=0.06). By 10 weeks post transplant, mice gained even more weight and levels were 377+/−51 ng/mL in LepR−/− mice receiving Psel+/+ bone marrow and 370+/−73 ng/mL in LepR−/− mice receiving Psel−/− bone marrow, p=0.87. Conclusions : These data suggest that the increase in sPsel observed in obesity is primarily derived from the endothelium and that this process is regulated by leukocyte Psgl-1.

scholarly journals Central overexpression of leptin antagonist reduces wheel running and underscores importance of endogenous leptin receptor activity in energy homeostasis

2009 ◽  
Vol 297 (5) ◽  
pp. R1254-R1261 ◽  
Author(s):  
Michael Matheny ◽  
Yi Zhang ◽  
Alexandra Shapiro ◽  
Nihal Tümer ◽  
Philip J. Scarpace
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Wheel Running ◽  
Receptor Activity ◽  
High Fat ◽  
Fat Feeding ◽  
Antagonist Group

We used recombinant adeno-associated virus (rAAV)-mediated gene delivery to overexpress a mutant of rat leptin yielding a protein that acts as a neutral leptin receptor antagonist. The long-term consequences of this overexpression on body weight homeostasis and physical activity, as assessed by voluntary wheel running (WR), were determined in F344 × Brown Norway (BN) rats. Leptin antagonist overexpression was confirmed by examination of mRNA levels in the hypothalamus. Food consumption and body weight gain were exacerbated in the antagonist group during both chow and high-fat feeding periods over the 192-day experiment. In a second experiment, a lower dose of antagonist vector was used that resulted in no change in food consumption but still increased body weight. The degree of antagonist overexpression was sufficient to partially block signal transducer and activator of transcription 3 (STAT3) phosphorylation due to administration of an acute submaximal dose of leptin. Rats were provided free access to running wheels for 4 days during both the chow and high-fat feeding periods. With both antagonist doses and during both chow and high-fat feeding, WR was substantially less with antagonist overexpression. In contrast, when leptin was overexpressed in the hypothalamus, WR activity was increased by greater than twofold. At death, adiposity and serum leptin levels were greater in the antagonist group. These data indicate that submaximal central leptin receptor blockade promotes obesity and diminishes WR activity. These findings underscore the critical role of unrestrained leptin receptor activity in long-term energy homeostasis and suggest that even minor disruption of leptin receptor function can promote obesity.

scholarly journals Effects of high fat diet and maternal binge-like alcohol consumption and their influence on cocaine response in female mice offspring

2020 ◽  
Author(s):  
L Duart-Castells ◽  
L Cantacorps ◽  
R López-Arnau ◽  
S Montagud-Romero ◽  
B Puster ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Fetal Alcohol Spectrum Disorders ◽  
Alcohol Exposure ◽  
Female Offspring ◽  
Blood Levels ◽  
Childhood And Adolescence ◽  
Standard Diet ◽  
Neurocognitive Deficits ◽  
High Fat ◽  
Increased Risk

Abstract BACKGROUD Prenatal alcohol exposure is a leading cause of neurobehavioral and neurocognitive deficits collectively known as fetal alcohol spectrum disorders (FASD), including eating disorders and increased risk for substance abuse as very common issues. In this context, the present study aimed to assess the interaction between alcohol exposure during gestation and lactation periods (PLAE) and a high fat diet (HFD) during childhood and adolescence. METHODS Pregnant C57BL/6 mice underwent a procedure for alcohol binge drinking during gestation and lactation periods. Subsequently, PLAE female offspring were fed with a HFD for 8 weeks and thereafter, nutrition-related parameters as well as their response to cocaine were assessed. RESULTS In our model, feeding young females with a HFD increased their triglyceride blood levels but did not induce an overweight compared to those fed with a standard diet. Moreover, PLAE affected how females responded to the fatty diet as they consumed less amount of food than water-exposed offspring, consistent with a lower gain of body weight. HFD increased the psychostimulant effects of cocaine. Surprisingly, PLAE reduced the locomotor responses to cocaine without modifying cocaine-induced reward. Moreover, PLAE prevented the striatal overexpression of cannabinoid 1 receptors induced by a HFD and induced an alteration of myelin damage biomarker in the prefrontal cortex, an effect that was mitigated by a HFD-based feeding. CONCLUSION Therefore, in female offspring, some effects triggered by one of these factors, PLAE or a HFD, were blunted by the other, suggesting a close interaction between the involved mechanisms.

scholarly journals Leprdb/+ Dams Protect Wild-type Male Offspring Bone Strength from the Detrimental Effects of a High-Fat Diet

Endocrinology ◽  
2020 ◽  
Vol 161 (8) ◽  
Author(s):  
Arin K Oestreich ◽  
Anthony Onuzuriuke ◽  
Xiaomei Yao ◽  
Omonseigho Talton ◽  
Yong Wang ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Maternal Obesity ◽  
Bone Geometry ◽  
Saline Group ◽  
Male Offspring ◽  
Material Strength ◽  
Wild Type ◽  
High Fat ◽  
Wild Type Male ◽  
Product Accumulation

Abstract The prevalence of maternal obesity is increasing at an alarming rate and increases the life-long risk of developing cardiometabolic disease in adult offspring. Leptin, an adipokine, is systemically elevated in the obese milieu. We recently showed that maternal hyperleptinemia without obesity improves offspring insulin sensitivity and glucose tolerance while protecting against weight gain on a high-fat, high-sugar (HFD). Here, we investigate the effect of maternal hyperleptinemia on offspring bone by using 2 independent maternal models. First, we compared wild-type (WT) offspring from severely hyperleptinemic Leprdb/+ (DB/+) dams with those from WT dams. In the second model, WT females were implanted with miniosmotic pumps that released either saline (group SAL) or leptin (group LEP; 650ng/hour) and the WT offspring were compared. At 23 weeks of age, a subset of offspring were challenged with a HFD for 8 weeks. When the offspring were 31 weeks of age, bone geometry, strength, and material properties were investigated. The HFD increased trabecular bone volume but decreased both total breaking strength and material strength of femora from the offspring of WT dams. However, male offspring of DB/+ dams were protected from the detrimental effects of a HFD, while offspring of LEP dams were not. Further material analysis revealed a modest decrease in advanced glycation end product accumulation coupled with increased collagen crosslinking in male offspring from DB/+ dams on a HFD. These data suggest that while maternal leptin may protect bone quality from the effects of a HFD, additional factors of the maternal environment controlled by leptin receptor signaling are likely also involved.

scholarly journals Reversal of increased mammary tumorigenesis by valproic acid and hydralazine in offspring of dams fed high fat diet during pregnancy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
F. de Oliveira Andrade ◽  
N. M. Nguyen ◽  
A. Warri ◽  
L. Hilakivi-Clarke
Keyword(s):  
Breast Cancer ◽  
Valproic Acid ◽  
Mammary Tumor ◽  
Dna Methyltransferase ◽  
Corn Oil ◽  
Control Diet ◽  
Combined Treatment ◽  
Female Offspring ◽  
High Fat ◽  
Increased Risk

AbstractMaternal or paternal high fat (HF) diet can modify the epigenome in germ cells and fetal somatic cells leading to an increased susceptibility among female offspring of multiple generations to develop breast cancer. We determined if combined treatment with broad spectrum DNA methyltransferase (DNMT) inhibitor hydralazine and histone deacetylase (HDAC) inhibitor valproic acid (VPA) will reverse this increased risk. C57BL/6 mouse dams were fed either a corn oil-based HF or control diet during pregnancy. Starting at age 7 weeks, female offspring were administered 3 doses of 7,12-dimethylbenz[a]anthracene (DMBA) to initiate mammary cancer. After last dose, offspring started receiving VPA/hydralazine administered via drinking water: no adverse health effects were detected. VPA/hydralazine reduced mammary tumor multiplicity and lengthened tumor latency in HF offspring when compared with non-treated HF offspring. The drug combination inhibited DNMT3a protein levels and increased expression of the tumor suppressor gene Cdkn2a/p16 in mammary tumors of HF offspring. In control mice not exposed to HF diet in utero, VPA/hydralazine increased mammary tumor incidence and burden, and elevated expression of the unfolded protein response and autophagy genes, including HIF-1α, NFkB, PERK, and SQSTM1/p62. Expression of these genes was already upregulated in HF offspring prior to VPA/hydralazine treatment. These findings suggest that breast cancer prevention strategies with HDAC/DNMT inhibitors need to be individually tailored.

scholarly journals Phenotypic Sexual Dimorphism in Response to Dietary Fat Manipulation in C57BL/6J Mice

2020 ◽  
Author(s):  
Isabel Casimiro ◽  
Natalie D. Stull ◽  
Sarah A. Tersey ◽  
Raghavendra Mirmira
Keyword(s):  
Sexual Dimorphism ◽  
Locomotor Activity ◽  
Glucose Tolerance ◽  
Food Consumption ◽  
High Fat Diet ◽  
Male Mice ◽  
High Fat ◽  
Β Cell ◽  
Male And Female ◽  
Female Mice

Abstract Background:Obesity and the metabolic syndrome are increasingly prevalent in society and their complications and response to treatment exhibit sexual dimorphism. Mouse models of high fat diet-induced obesity are commonly used for both mechanistic and therapeutic studies of metabolic disease and diabetes. However, the inclusion of female mammals in obesity research has not been a common practice, and has resulted in a paucity of data regarding the effect of sex on metabolic parameters and its applicability to humans. Methods:Here we analyzed male and female C57BL/6J mice beginning at 4 weeks of age that were placed on a low-fat diet (LFD, 10% calories from fat), a Western Diet (WD, 45% calories from fat), or a high fat diet (HFD, 60% calories from fat). Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were performed. Results:Both male and female C57BL/6J mice had similar increases in total percent body weight gain with both WD and HFD compared to LFD, however, male mice gained weight earlier upon HFD or WD feeding compared to female mice. Male mice exhibited a decrease in both food consumption and activity with either WD or HFD compared to LFD, whereas female mice did not exhibit any differences in food intake and minimal changes in locomotor activity on any diet. Glucose tolerance tests performed at 4, 12 and 20 weeks of dietary intervention revealed impaired glucose tolerance that was worse in male mice compared to females. Furthermore, male mice exhibited an increase in pancreatic β cell area as well as reduced insulin sensitivity after HFD feeding compared to WD or LFD, whereas female mice did not. Conclusions:Male and female C57BL/6J mice exhibited strikingly different responses in weight, food consumption, locomotor activity, and β cell adaptation upon dietary manipulation, with the latter exhibiting less striking phenotypic changes. We conclude that the nature of these responses emphasizes the need to contextualize studies of obesity pathophysiology and treatment with respect to sex.

Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones

2019 ◽  
Vol 89 (1-2) ◽  
pp. 45-54
Author(s):  
Akemi Suzuki ◽  
André Manoel Correia-Santos ◽  
Gabriela Câmara Vicente ◽  
Luiz Guillermo Coca Velarde ◽  
Gilson Teles Boaventura
Keyword(s):  
Thyroid Hormones ◽  
High Fat Diet ◽  
Female Offspring ◽  
Flaxseed Oil ◽  
Diabetic Rats ◽  
High Fat ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Flaxseed Flour ◽  
Maternal Consumption

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.

Non-Fasting Factor VII Coagulant Activity (FVII:C) Increased by High-Fat Diet

1994 ◽  
Vol 71 (06) ◽  
pp. 755-758 ◽  
Author(s):  
E M Bladbjerg ◽  
P Marckmann ◽  
B Sandström ◽  
J Jespersen
Keyword(s):  
High Fat Diet ◽  
Fat Content ◽  
Factor Vii ◽  
Amidolytic Activity ◽  
High Fat ◽  
Low Fat Diet ◽  
Increased Risk ◽  
Coagulant Activity ◽  
High Fat Diets ◽  
Fat Diets

SummaryPreliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20% or 50% of energy). The 2 diets were served on 2 consecutive days. Blood samples were collected at 8.00 h, 16.30 h and 19.30 h, and analysed for triglycerides, FVII coagulant activity using human (FVII:C) or bovine thromboplastin (FVII:Bt), and FVII amidolytic activity (FVIPAm). The ratio FVII:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII: Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet. The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals Effects of B.1.1.7 and B.1.351 on COVID-19 Dynamics: A Campus Reopening Study

2021 ◽  
Author(s):  
Kevin Linka ◽  
Mathias Peirlinck ◽  
Amelie Schäfer ◽  
Oguz Ziya Tikenogullari ◽  
Alain Goriely ◽  
...  
Keyword(s):  
Online Education ◽  
The United States ◽  
Wild Type ◽  
Seir Model ◽  
Population Mixing ◽  
Santa Clara County ◽  
Increased Risk ◽  
Controversial Topic ◽  
Almost All ◽  
Local Reproduction

AbstractThe timing and sequence of safe campus reopening has remained the most controversial topic in higher education since the outbreak of the COVID-19 pandemic. By the end of March 2020, almost all colleges and universities in the United States had transitioned to an all online education and many institutions have not yet fully reopened to date. For a residential campus like Stanford University, the major challenge of reopening is to estimate the number of incoming infectious students at the first day of class. Here we learn the number of incoming infectious students using Bayesian inference and perform a series of retrospective and projective simulations to quantify the risk of campus reopening. We create a physics-based probabilistic model to infer the local reproduction dynamics for each state and adopt a network SEIR model to simulate the return of all undergraduates, broken down by their year of enrollment and state of origin. From these returning student populations, we predict the outbreak dynamics throughout the spring, summer, fall, and winter quarters using the inferred reproduction dynamics of Santa Clara County. We compare three different scenarios: the true outbreak dynamics under the wild-type SARS-CoV-2, and the hypothetical outbreak dynamics under the new COVID-19 variants B.1.1.7 and B.1.351 with 56% and 50% increased transmissibility. Our study reveals that even small changes in transmissibility can have an enormous impact on the overall case numbers. With no additional countermeasures, during the most affected quarter, the fall of 2020, there would have been 203 cases under baseline reproduction, compared to 4727 and 4256 cases for the B.1.1.7 and B.1.351 variants. Our results suggest that population mixing presents an increased risk for local outbreaks, especially with new and more infectious variants emerging across the globe. Tight outbreak control through mandatory quarantine and test-trace-isolate strategies will be critical in successfully managing these local outbreak dynamics.

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