scholarly journals SAT-287 Mild Perinatal Undernutrition Results in Underweight Pups and a Premature Neonatal Leptin Surge

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tiffany K Miles ◽  
Melody Lyn Allensworth ◽  
Ana Rita Silva Moreira ◽  
Angela Katherine Odle ◽  
Anessa Haney ◽  
...  
Keyword(s):  
Cell Metabolism ◽  
Caloric Intake ◽  
Male Rat ◽  
Metabolic Dysfunction ◽  
Leptin Receptors ◽  
Gh Secretion ◽  
Maternal Undernutrition ◽  
Rat Pups ◽  
The Impact

Abstract Malnutrition causes dysregulated pituitary function, which may in part be due to lowered leptin signals. We showed that loss of somatotrope leptin receptors in mice reduces growth hormone (GH) secretion and promotes metabolic dysfunction in adults. More recently, we showed that adult male mice fasted for 12 or 24 hours also had significantly lowered GH secretion, which correlated with a 94% reduction in serum leptin. Malnutrition may result in changes in the leptin surge during neonatal development in rodents or the third trimester in humans. Severe (50% reduction) maternal undernutrition (1) blunted the surge in rodents, however less severe undernutrition (30% reduction) caused a premature leptin surge (2). Both studies reported that pups showed metabolic dysfunction as adults. In our studies of leptin regulation of somatotropes, we tested the more severe calorie restriction model and discovered significant pup and maternal loss. We then elected to develop a milder undernutrition model, which may relate more closely to society’s nutritional challenges with the objective of determining if the timing of the leptin surge had shifted. This maternal undernutrition study consisted of dams fed ad libitum (fed) and pair fed dams receiving 20% reduced caloric intake (undernourished). Undernutrition started at E15 and ended with sacrifice at various times during the leptin surge. While nursing, the undernourished dams did not lose weight, but their weight gain was reduced to 45% of that of fed dams. We have collected data from 177 neonatal pups and 19 fed or undernourished dams. At PND5 and PND10, pups from undernourished moms weighed significantly less (16.3% and 21.8%) than pups from fed dams. Additionally, weanlings (PND 21) from underfed dams exhibited a 28.04% reduction in weight and an 8.43% reduction in nose to anus length (p = 0.0005) compared to pups from control fed dams. The timing of the leptin surge in pups from fed dams was normal in female pups. However, pups from mildly undernourished dams had “premature” leptin surges that peaked 2 days earlier than normal. Ongoing studies are testing metabolic function in these mice, as adults, to determine their sensitivity to a 45% high fat diet and the impact on somatotrope functions. This model demonstrates that even a 20% reduction in nutrition will negatively impact offspring and shift the timing of the leptin surge. 1. Delahaye F, Breton C, Risold PY, Enache M, Dutriez-Casteloot I, Laborie C, Lesage J, Vieau D. Maternal perinatal undernutrition drastically reduces postnatal leptin surge and affects the development of arcuate nucleus proopiomelanocortin neurons in neonatal male rat pups. Endocrinology 2008; 149:470-475 2. Yura S, Itoh H, Sagawa N, Yamamoto H, Masuzaki H, Nakao K, Kawamura M, Takemura M, Kakui K, Ogawa Y. Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell metabolism 2005; 1:371-378

scholarly journals The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1046
Author(s):  
Jorge Martinez ◽  
Patricio C. Smith
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Cell Metabolism ◽  
Breast Tumors ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Desmoplastic Reaction ◽  
The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

scholarly journals Gestational Monosodium Glutamate Exposure Effects on Anogenital Distance of Male Rat Pups

2021 ◽  
Vol 53 (2) ◽  
Author(s):  
Amelya Permata Sari ◽  
Cimi Ilmiawati ◽  
Mohamad Reza
Keyword(s):  
Monosodium Glutamate ◽  
Maternal Serum ◽  
Male Rat ◽  
High Dose ◽  
Dependent Manner ◽  
Pregnant Rats ◽  
Anogenital Distance ◽  
Estrogen Level ◽  
Rat Pups ◽  
The Impact

High-dose Monosodium Glutamate (MSG) expo sure increases the estrogen level in pregnant rats. However, there are limited data available on whether the MSG-related maternal hormonal effects can affect male litters' genitalia phenotype. This study aimed to analyze the impact of MSG on estrogen level in pregnant rats and anogenital distance in male pups. Experiment for this study was performed at the animal facility of Biomedical Laboratory at the Faculty of Medicine, Universitas Andalas, from April 2019 to February 2020. Pregnant Wistar rats were given MSG orally at 2 and 4 mg/g body weight (BW) for 20 days. On day 21, pregnant rats were sacrificed and blood was drawn intracardially. Estradiol serum level was measured by ELISA. Male pups were counted, and the anogenital distance (AGD) was measured. Maternal serum estradiol levels were statistically analyzed by One-Way ANOVA and the AGD of male litters were analyzed by the Kruskal-Wallis test. Results showed that perinatal MSG exposure increased the estradiol level (26.3±4.5 pg/ml; 37.5±6.7 pg/ml; 62.1±8.2 pg/ml in control, 2 mg/g BW, and 4 mg/g BW group, respectively [mean±SD; p=<0.001]) and decreased the AGD (4 mm; 3 mm; 1.5 mm in control, 2 mg/g BW, and 4 mg/gBW group, respectively [median; p=<0.01]) in a dose-dependent manner. Thus, MSG exposure during pregnancy is a risk factor for male rat feminization.

scholarly journals Maternal Microbiota Transfer Programs Offspring Eating Behavior

2021 ◽  
Vol 12 ◽  
Author(s):  
Anne-Lise Pocheron ◽  
Gwenola Le Dréan ◽  
Helene Billard ◽  
Thomas Moyon ◽  
Anthony Pagniez ◽  
...  
Keyword(s):  
Eating Behavior ◽  
Intestinal Microbiota ◽  
Caloric Intake ◽  
Microbiota Composition ◽  
Sprague Dawley ◽  
Family Culture ◽  
Gut Colonization ◽  
Main Determinants ◽  
The Impact

Understanding the link between mother’s obesity and regulation of the child’s appetite is a prerequisite for the design of successful preventive strategies. Beyond the possible contributions of genetic heritage, family culture, and hormonal and metabolic environment during pregnancy, we investigate in the present paper the causal role of the transmission of the maternal microbiotas in obesity as microbiotas differ between lean and obese mothers, maternal microbiotas are the main determinants of a baby’s gut colonization, and the intestinal microbiota resulting from the early colonization could impact the feeding behavior of the offspring with short- and long-term consequences on body weight. We thus investigated the potential role of vertical transfers of maternal microbiotas in programming the eating behavior of the offspring. Selectively bred obese-prone (OP)/obese-resistant (OR) Sprague-Dawley dams were used since differences in the cecal microbiota have been evidenced from males of that strain. Microbiota collected from vagina (at the end of gestation), feces, and milk (at postnatal days 1, 5, 10, and 15) of OP/OR dams were orally inoculated to conventional Fischer F344 recipient pups from birth to 15 days of age to create three groups of pups: F-OP, F-OR, and F-Sham group (that received the vehicle). We first checked microbiotal differences between inoculas. We then assessed the impact of transfer (from birth to adulthood) onto the intestinal microbiota of recipients rats, their growth, and their eating behavior by measuring their caloric intake, their anticipatory food reward responses, their preference for sweet and fat tastes in solutions, and the sensations that extend after food ingestion. Finally, we searched for correlation between microbiota composition and food intake parameters. We found that maternal transfer of microbiota differing in composition led to alterations in pups’ gut microbiota composition that did not last until adulthood but were associated with specific eating behavior characteristics that were predisposing F-OP rats to higher risk of over consuming at subsequent periods of their life. These findings support the view that neonatal gut microbiotal transfer can program eating behavior, even without a significant long-lasting impact on adulthood microbiota composition.

scholarly journals New Insights into the Role of Histone Changes in Aging

2020 ◽  
Vol 21 (21) ◽  
pp. 8241
Author(s):  
Sun-Ju Yi ◽  
Kyunghwan Kim
Keyword(s):  
Chromatin Remodeling ◽  
Regulatory Networks ◽  
Genome Instability ◽  
Histone Variants ◽  
Cellular Tissue ◽  
Metabolic Dysfunction ◽  
Loss Of Function ◽  
Epigenetic Regulators ◽  
The Impact

Aging is the progressive decline or loss of function at the cellular, tissue, and organismal levels that ultimately leads to death. A number of external and internal factors, including diet, exercise, metabolic dysfunction, genome instability, and epigenetic imbalance, affect the lifespan of an organism. These aging factors regulate transcriptome changes related to the aging process through chromatin remodeling. Many epigenetic regulators, such as histone modification, histone variants, and ATP-dependent chromatin remodeling factors, play roles in chromatin reorganization. The key to understanding the role of gene regulatory networks in aging lies in characterizing the epigenetic regulators responsible for reorganizing and potentiating particular chromatin structures. This review covers epigenetic studies on aging, discusses the impact of epigenetic modifications on gene expression, and provides future directions in this area.

scholarly journals Impact of Neonatal Manipulation of Androgen Receptor Function on Endocrine-Metabolic Programming in the Juvenile Female Rat

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Luisina Ongaro ◽  
Andres Giovambattista ◽  
Eduardo Spinedi
Keyword(s):  
Androgen Receptor ◽  
Metabolic Effects ◽  
Female Rat ◽  
Ovarian Dysfunction ◽  
Juvenile Female ◽  
Rat Pups ◽  
Energy Store ◽  
The Impact ◽  
Neuroendocrine Functions

The impact of neonatal androgen receptor (AR) stimulation/blockage, due to testosterone propionate (TP)/AR antagonist treatment, on individual anthropometry and neuroendocrine-metabolic function was evaluated in the juvenile female rat. Pups (age 5 days) were s.c. injected with TP (1.25 mg), flutamide (F; 1.75 mg), and TP + F or vehicle (control, CT) and studied on day 30 of age. Body weight (BW), parametrial adipose tissue (PMAT) mass, food intake, adipoinsular axis, and steroidogenic functions were examined. Opposite to TP-rats, F-treated rats developed hypophagia, grew slowly (BW and PMAT), and displayed heightened peripheral insulin sensitivity. These F effects were abrogated in TP + F animals. Accordingly, TP rats displayed hyperleptinemia, an effect fully prevented by F cotreatment. Finally, androgen-treated animals bore an irreversible ovarian dysfunction (reduced circulating levels of 17HOP4 and ovary 17HOP4 content and P450c17 mRNA abundance). These data indicate that early stimulation of AR enhanced energy store, blockage of AR activity resulted in some beneficial metabolic effects, and neonatally androgenized rats developed a severe ovarian dysfunction. Our study highlights the important role of AR in the early organizational programming of metabolic and neuroendocrine functions.

scholarly journals Maternal Perinatal Undernutrition Drastically Reduces Postnatal Leptin Surge and Affects the Development of Arcuate Nucleus Proopiomelanocortin Neurons in Neonatal Male Rat Pups

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 470-475 ◽  
Author(s):  
Fabien Delahaye ◽  
Christophe Breton ◽  
Pierre-Yves Risold ◽  
Mihaela Enache ◽  
Isabelle Dutriez-Casteloot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Levels ◽  
Metabolic Disorders ◽  
Arcuate Nucleus ◽  
Nerve Fibers ◽  
Male Rats ◽  
Male Rat ◽  
Maternal Undernutrition ◽  
Rat Pups ◽  
Plasma Leptin

A growing body of evidence suggests that maternal undernutrition sensitizes the offspring to the development of energy balance metabolic disorders such as type 2 diabetes, dyslipidemia, and obesity. The present study aimed at examining the impact of maternal undernutrition on leptin plasma levels in newborn male rats and on the arcuate nucleus proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons that are major leptin targets. Using a model of perinatal maternal 50% food-restricted diet (FR50) in the rat, we evaluated leptin plasma levels and hypothalamic POMC and NPY gene expression from postnatal day (PND) 4 to PND30 in both control and FR50 offspring. In control rats, a postnatal peak of plasma leptin was observed between PND4 and PND14 that reached a maximal value at PND10 (5.17 ± 0.53 ng/ml), whereas it was dramatically reduced in FR50 pups with the higher concentration at PND7 (0.93 ± 0.23 ng/ml). In FR50 animals, using semiquantitative RT-PCR and in situ hybridization, we showed that the hypothalamic POMC mRNA level was decreased from PND14 until PND30, whereas NPY gene expression was not significantly modified. In PND21 FR50 animals, we observed strikingly reduced immunoreactive β-endorphin nerve fibers projecting to the hypothalamic paraventricular nucleus without affecting NPY projections. Our data showed that maternal undernutrition drastically reduces the postnatal surge of plasma leptin, disturbing particularly the hypothalamic wiring as well as the gene expression of the anorexigenic POMC neurons in male rat pups. These alterations might contribute to the adult metabolic disorders resulting from perinatal growth retardation.

Diurnal Variations of Plasma Growth Hormone and Brain Monoamines in Adult Male Rats

1973 ◽  
Vol 51 (12) ◽  
pp. 890-892 ◽  
Author(s):  
R. Collu ◽  
J. C. Jéquier ◽  
J. Letarte ◽  
G. Leboeuf ◽  
J. R. Ducharme
Keyword(s):  
Growth Hormone ◽  
Adult Male ◽  
Physiological Role ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Growth Hormone ◽  
Gh Secretion ◽  
Adult Male Rat ◽  
Plasma Gh

Brain levels of monoamines (MA) in the adult male rat show a diurnal pattern of secretion with noradrenaline (NA) and serotonin (5-HT) reaching a peak at 1300 and 1800, respectively, and dopamine (DA) showing a bimodal pattern with peaks at 0500 and 1800. Plasma growth hormone (GH) values fluctuate widely during the nycthemeral period. Statistically significant correlations between plasma GH and brain MA levels, confirming the existence of a physiological role of MA in the control of GH secretion, could not be demonstrated in the present study.

Neonatal rat dietary carbohydrate affects pancreatic islet insulin secretion in adults and progeny

1995 ◽  
Vol 269 (4) ◽  
pp. E739-E744 ◽  
Author(s):  
S. G. Laychock ◽  
S. Vadlamudi ◽  
M. S. Patel
Keyword(s):  
Pancreatic Islet ◽  
First Generation ◽  
Cell Metabolism ◽  
Neonatal Rat ◽  
Male Rat ◽  
Female Rat ◽  
Adult Rats ◽  
Rat Pups ◽  
Glucose Sensitivity ◽  
Isocaloric Diets

Neonatal rat pups were artificially reared on isocaloric diets high in carbohydrate (HC) or high in fat (HF) or were naturally reared on mother's milk (MF). The HC adult rats were hyperinsulinemic, normoglycemic, and obese. This study investigates pancreatic islet insulin release (IR) of the adult first-generation (1-) diet-regulated animals and their second-generation (2-) progeny. Male rat 1-HC islets had higher basal IR than either 1-MF or 1-HF control groups. In addition, glucose (17 mM) failed to increase IR above basal values in 1-HC islets, whereas it stimulated IR in 1-MF and 1-HF islets. Similar secretory responses were evoked by 2-ketoisocaproic acid (2-KIC). Female rat 1-MF and 1-HF islets also had higher glucose-stimulated IR compared with 1-HC islets. Male rat 2-HC islets had higher basal IR and reduced sensitivity to glucose and 2-KIC compared with 2-MF islets, which coincided with hyperinsulinemia. Glyceraldehyde-3-phosphate dehydrogenase activity in 1-HC and 2-HC islets was higher than in MF islets. These data suggest that basal IR is higher in islets isolated from animals reared as neonates on a diet high in carbohydrate. Alterations in beta-cell metabolism and secretion probably contribute to the hyperinsulinemia, reduced glucose sensitivity, and glucose intolerance characteristic of this rat model.

scholarly journals Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation

2013 ◽  
Vol 124 (8) ◽  
pp. 491-507 ◽  
Author(s):  
Silvia Bijland ◽  
Sarah J. Mancini ◽  
Ian P. Salt
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Protein Kinase ◽  
Caloric Intake ◽  
Whole Body ◽  
Acid Oxidation ◽  
Metabolic Dysfunction ◽  
Nutrient Metabolism ◽  
Amp Activated Protein Kinase

AMPK (AMP-activated protein kinase) is a key regulator of cellular and whole-body energy balance. AMPK phosphorylates and regulates many proteins concerned with nutrient metabolism, largely acting to suppress anabolic ATP-consuming pathways while stimulating catabolic ATP-generating pathways. This has led to considerable interest in AMPK as a therapeutic target for the metabolic dysfunction observed in obesity and insulin resistance. The role of AMPK in skeletal muscle and the liver has been extensively studied, such that AMPK has been demonstrated to inhibit synthesis of fatty acids, cholesterol and isoprenoids, hepatic gluconeogenesis and translation while increasing fatty acid oxidation, muscle glucose transport, mitochondrial biogenesis and caloric intake. The role of AMPK in the other principal metabolic and insulin-sensitive tissue, adipose, remains poorly characterized in comparison, yet increasing evidence supports an important role for AMPK in adipose tissue function. Obesity is characterized by hypertrophy of adipocytes and the development of a chronic sub-clinical pro-inflammatory environment in adipose tissue, leading to increased infiltration of immune cells. This combination of dysfunctional hypertrophic adipocytes and a pro-inflammatory environment contributes to insulin resistance and the development of Type 2 diabetes. Exciting recent studies indicate that AMPK may not only influence metabolism in adipocytes, but also act to suppress this pro-inflammatory environment, such that targeting AMPK in adipose tissue may be desirable to normalize adipose dysfunction and inflammation. In the present review, we discuss the role of AMPK in adipose tissue, focussing on the regulation of carbohydrate and lipid metabolism, adipogenesis and pro-inflammatory pathways in physiological and pathophysiological conditions.

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