scholarly journals Neuroendocrine Basis for Disrupted Ovarian Cyclicity in Females During Chronic Undernutrition: A Mouse Model

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A546-A546
Author(s):  
Kirollos S Tadrousse ◽  
Richard B McCosh ◽  
Michael J Kreisman ◽  
Kellie M Breen
Keyword(s):  
Molecular Mechanisms ◽  
Control Diet ◽  
Baseline Period ◽  
Ovarian Cycle ◽  
Reproductive Capacity ◽  
Cell Populations ◽  
Feed Restriction ◽  
Lh Surge ◽  
Chronic Undernutrition ◽  
Ovarian Cyclicity

Abstract Chronic undernutrition is a type of metabolic stress that impairs reproduction across species and, in women, is implicated in the development of functional hypothalamic amenorrhea. Although the tight coupling of energy balance to reproductive capacity is recognized in principle, the neuroendocrine loci and molecular mechanisms that mediate ovarian cycle dysfunction during undernutrition remain poorly understood. Ovarian cyclicity is dependent on a population of kisspeptin (Kiss1) neurons in arcuate nucleus (ARCKiss1) for luteinizing hormone (LH) pulses and in the anteroventral periventricular nucleus (AVPVKiss1) for LH surge secretion. Here, we present a series of studies in which we tested the hypothesis that inhibition of both Kiss1 cell populations underlies the impairment of the cycle by undernutrition. During a baseline period, body weight, feed intake, and ovarian cycle stage (via vaginal cytology) were evaluated in female c57bl6 mice. Then, animals were randomly assigned into one of two groups (n=6-8/grp): 1) ad libitum fed controls or 2) feed restricted (70% of feed consumed during the baseline period). Control animals displayed clear and regular cycles throughout the 4-week treatment period. In contrast, feed restriction caused a significant and rapid cessation of ovarian cyclicity (4.8±0.3 vs. 1.5±0.5 estrus cycles/4 weeks; control vs. restricted, p<0.05), causing all females to enter and remain mostly in diestrus. Based on these results, we conducted two experiments to directly test the hypothesis that undernutrition inhibits both modes of LH secretion (and both Kiss1 cell populations) using two well-defined estradiol (E) replacement paradigms. We first evaluated LH pulses in mice that were ovariectomized and implanted subcutaneously with a pellet containing a diestrus level of E (100 ng, OVX+LowE). Following 3 days of feed restriction or control diet (n=3/grp), serial blood samples were collected every 8 min for 88 min. Undernutrition prevented LH pulses and significantly reduced mean LH (5.2±0.6 vs. 0.6±0.2 ng/mL; control vs. restricted, p<0.05). Fixed neural tissue was evaluated by immunohistochemistry to determine whether undernutrition impairs ARCKiss1 neuronal activation, using c-Fos as a marker. The percent of ARCKiss1 neurons expressing cFos was reduced by 90% (p<0.05). We next evaluated the LH surge. After 3 days, control or feed restricted mice were OVX and implanted subcutaneously with a surge-inducing estradiol implant (OVX+HighE, 1 µg, n=3-4/grp). Undernutrition completely blocked the E-induced LH surge (1.9±0.3 vs. 0.2±0.02 ng/mL; control vs. restricted, p<0.05) and diminished Kiss1 mRNA abundance in micropunches of the AVPV (42%, p<0.05). Collectively, these studies clearly show that undernutrition impairs both ARCKiss1 control of LH pulses and AVPVKiss1 induction of the LH surge, via mechanisms that remain to be identified.

Neuroendocrine Basis for Disrupted Ovarian Cyclicity in Female Mice During Chronic Undernutrition

Endocrinology ◽  
2021 ◽  
Author(s):  
Michael J Kreisman ◽  
Kirollos S Tadrousse ◽  
Richard B McCosh ◽  
Kellie M Breen
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Stress ◽  
Ovarian Cycle ◽  
Reproductive Capacity ◽  
Lh Surge ◽  
Tightly Coupled ◽  
Estrous Cyclicity ◽  
Chronic Undernutrition ◽  
Multiple Species ◽  
Ovarian Cyclicity

Abstract Chronic undernutrition is a type of metabolic stress that impairs reproduction in multiple species. Although energy balance and female reproductive capacity is recognized as tightly coupled, the neuroendocrine loci and molecular mechanisms that mediate ovarian cycle dysfunction during chronic undernutrition in adult females remain poorly understood. Here, we present a series of studies in which we tested the hypothesis that inhibition of kisspeptin (Kiss1) neurons, which are critical for controlling luteinizing hormone (LH) pulses and the preovulatory LH surge in females, underlies the impairment of the ovarian cycle by undernutrition. We first investigated the effect of chronic undernutrition (70% of unrestricted feed intake) on estrous cyclicity in intact female c57bl6 mice. Undernutrition caused a rapid cessation of ovarian cyclicity during the two-week treatment, suppressing ovarian steroidogenesis and inhibiting ovulation. Using two well-defined estradiol replacement paradigms, we directly tested the hypothesis that undernutrition inhibits Kiss1 neurons in the arcuate nucleus (ARC Kiss1) which are required for LH pulses and in the anteroventral periventricular nucleus (AVPV Kiss1) which are necessary for LH surge secretion. Undernutrition prevented LH pulses and impaired ARC Kiss1 neuronal activation, using c-Fos as a marker, in ovariectomized females subcutaneously implanted with a pellet containing a diestrus-like level of estradiol. In addition, undernutrition completely blocked the estradiol-induced LH surge and diminished Kiss1 mRNA abundance, without decreasing Erα, in micropunches of the AVPV. Collectively, these studies demonstrate that undernutrition disrupts ovarian cyclicity in females via impairment of both ARC Kiss1 control of LH pulses and AVPV Kiss1 induction of the LH surge.

scholarly journals Quantitative and qualitative feed restriction for broilers

2021 ◽  
Vol 10 (12) ◽  
pp. e339101220447
Author(s):  
Thiago de Sousa Melo ◽  
José Humberto Vilar da Silva ◽  
José Jordão Filho ◽  
Fernando Guilherme Perazzo Costa ◽  
Patrícia Emília Naves Givisiez ◽  
...  
Keyword(s):  
Crude Protein ◽  
Control Diet ◽  
Essential Amino Acids ◽  
Feed Restriction ◽  
Broiler Performance ◽  
Randomized Design ◽  
Ad Libitum ◽  
Completely Randomized Design ◽  
Al Treatment ◽  
Economical Alternative

The objective of this study is to evaluate the influence of five feed restriction programs (FRP) on broiler performance and carcass yield. 425 Cobb 500® broilers were distributed in a completely randomized design with five FRPs and five replicates with 17 broilers. The FRPs were: Program 1 (P1): consumption ad libitum (AL) of control diet from 14 to 42 days; P2: quantitative restriction (QTR) of 10% of AL consumption from 14 to 28 days and AL consumption from 29 to 42 days; P3: AL consumption from 14 to 28 days and QTR from 29 to 42 days; P4: qualitative restriction (QLR) of 10% of the level of crude protein and essential amino acids from 14 to 28 days and AL consumption from 29 to 42 days; and P5: AL consumption from 14 to 28 days and QLR from 29 to 42 days. The broilers of the AL treatment gained more weight (p≤0.01), but had a similar FCR (P>0.05) compared to broilers submitted to QTR from 29 to 42 days. In addition, broilers fed QTR from 14 to 28 days presented a lower FI and a better FCR (p≤0.01) in relation to broilers fed QLR of 14 to 28 (P4) and 29 to 42 days (P5). The broilers fed QTR of 14 to 28 days diet presented a similar FCR as broilers fed AL. The 10% reduction in AL consumption of 14 to 28 d is a viable economical alternative to feed broilers up to 42 days of age.

scholarly journals Stem Cell Concept in Thyroid Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Cihan Zamur ◽  
Uğur Topal ◽  
Harun Özdemir ◽  
Serdar Altınay
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Thyroid Cancer ◽  
Thyroid Gland ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Clinical Results ◽  
Cell Populations ◽  
Cellular Origin ◽  
Rare Cells

The most frequently diagnosed endocrine cancer, which causes more deaths than any other endocrine cancer, is thyroid cancer. Cancer stem cells are rare cells found in tumors that can regenerate themselves, phenotypically leads to various tumor cell populations and trigger tumorigenesis. Cancer stem cells have been identified in many cancers, including thyroid cancer. Having an understanding of the molecular mechanisms which control the biology of cancer stem cells and the disease processes will help us in designing more rational targeted therapies for aggressive thyroid cancers. In this review, we aimed to present the current accepted knowledge about thyroid stem cells, information regarding the cellular origin of thyroid cancer stem cells, and the clinical results of cancer stem cells present in the thyroid gland.

scholarly journals Persistent Epigenetic Reprogramming of Sweet Taste by Diet

2020 ◽  
Author(s):  
Anoumid Vaziri ◽  
Morteza Khabiri ◽  
Brendan T. Genaw ◽  
Christina E. May ◽  
Peter L. Freddolino ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Sweet Taste ◽  
Taste Perception ◽  
Epigenetic Mechanism ◽  
High Sugar ◽  
Epigenetic Regulator ◽  
Transcriptional Changes ◽  
Gustatory Neurons

AbstractDiets rich in sugar, salt, and fat alter taste perception and food intake, leading to obesity and metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here we show that in response to a high sugar diet, the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms the sensory neurons of D. melanogaster flies to reduce sweet sensation and promote obesity. In animals fed high sugar, the binding of PRC2.1 to the chromatin of the sweet gustatory neurons is redistributed to repress a developmental transcriptional network that modulates the responsiveness of these cells to sweet stimuli, reducing sweet sensation. Importantly, half of these transcriptional changes persist despite returning the animals to a control diet, causing a permanent decrease in sweet taste. Our results uncover a new epigenetic mechanism that, in response to the dietary environment, regulates neural plasticity and feeding behavior to promote obesity.

A calcineurin- and NFAT-dependent pathway regulates Myf5 gene expression in skeletal muscle reserve cells

2001 ◽  
Vol 114 (2) ◽  
pp. 303-310 ◽  
Author(s):  
B.B. Friday ◽  
G.K. Pavlath
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Satellite Cell ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Fiber Type ◽  
Calcium Ionophore ◽  
Cell Populations ◽  
Mrna Levels ◽  
Dependent Pathway

Myf5 is a member of the muscle regulatory factor family of transcription factors and plays an important role in the determination, development, and differentiation of skeletal muscle. However, factors that regulate the expression and activity of Myf5 itself are not well understood. Recently, a role for the calcium-dependent phosphatase calcineurin was suggested in three distinct pathways in skeletal muscle: differentiation, hypertrophy, and fiber-type determination. We propose that one downstream target of calcineurin and the calcineurin substrate NFAT in skeletal muscle is regulation of Myf5 gene expression. For these studies, we used myotube cultures that contain both multinucleated myotubes and quiescent, mononucleated cells termed ‘reserve’ cells, which share many characteristics with satellite cells. Treatment of such myotube cultures with the calcium ionophore ionomycin results in an approximately 4-fold increase in Myf5 mRNA levels, but similar effects are not observed in proliferating myoblast cultures indicating that Myf5 is regulated by different pathways in different cell populations. The increase in Myf5 mRNA levels in myotube cultures requires the activity of calcineurin and NFAT, and can be specifically enhanced by overexpressing the NFATc isoform. We used immunohistochemical analyses and fractionation of the cell populations to demonstrate that the calcium regulated expression of Myf5 occurs in the mononucleated reserve cells. We conclude that Myf5 gene expression is regulated by a calcineurin- and NFAT-dependent pathway in the reserve cell population of myotube cultures. These results may provide important insights into the molecular mechanisms responsible for satellite cell activation and/or the renewal of the satellite cell pool following activation and proliferation.

scholarly journals Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications

2012 ◽  
Vol 56 (9) ◽  
pp. 597-607 ◽  
Author(s):  
Gilberto Paz-Filho ◽  
Claudio Mastronardi ◽  
Carina Bertoldi Franco ◽  
Kevin Boyang Wang ◽  
Ma-Li Wong ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Biological Activity ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Cell Populations ◽  
Clinical Implications ◽  
Intracellular Proteins ◽  
Intracellular Pathways ◽  
Immune Defects ◽  
Biological Actions

Leptin, the adipokine produced mainly by the white adipose tissue, plays important roles not only in the regulation of food intake, but also in controlling immunity and inflammation. It has been widely demonstrated that the absence of leptin leads to immune defects in animal and human models, ultimately increasing mortality. Leptin also regulates inflammation by means of actions on its receptor, that is widely spread across different immune cell populations. The molecular mechanisms by which leptin determines its biological actions have also been recently elucidated, and three intracellular pathways have been implicated in leptin actions: JAK-STAT, PI3K, and ERK 1/2. These pathways are closely regulated by intracellular proteins that decrease leptin biological activity. In this review, we discuss the molecular mechanisms by which leptin regulates immunity and inflammation, and associate those mechanisms with chronic inflammatory disorders. Arq Bras Endocrinol Metab. 2012;56(9):597-607

scholarly journals Persistent epigenetic reprogramming of sweet taste by diet

2020 ◽  
Vol 6 (46) ◽  
pp. eabc8492
Author(s):  
Anoumid Vaziri ◽  
Morteza Khabiri ◽  
Brendan T. Genaw ◽  
Christina E. May ◽  
Peter L. Freddolino ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Sweet Taste ◽  
Taste Perception ◽  
Epigenetic Mechanism ◽  
High Sugar ◽  
Epigenetic Regulator ◽  
Transcriptional Changes ◽  
Gustatory Neurons

Diets rich in sugar, salt, and fat alter taste perception and food preference, contributing to obesity and metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here, we show that in response to a high sugar diet, the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms the sensory neurons of Drosophila melanogaster flies to reduce sweet sensation and promote obesity. In animals fed high sugar, the binding of PRC2.1 to the chromatin of the sweet gustatory neurons is redistributed to repress a developmental transcriptional network that modulates the responsiveness of these cells to sweet stimuli, reducing sweet sensation. Half of these transcriptional changes persist despite returning the animals to a control diet, causing a permanent decrease in sweet taste. Our results uncover a new epigenetic mechanism that, in response to the dietary environment, regulates neural plasticity and feeding behavior to promote obesity.

scholarly journals Blockade of High-Fat Diet Proteomic Phenotypes using Exercise as Prevention or Treatment

2020 ◽  
pp. mcp.TIR120.002343
Author(s):  
Sergio F Martinez-Huenchullan ◽  
Isaac Shipsey ◽  
Luke Hatchwell ◽  
Danqing Min ◽  
Stephen M Twigg ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Saturated Fat ◽  
Interval Training ◽  
Plasma Proteome ◽  
High Fat ◽  
Endurance Running ◽  
Interactive Visualizations

The increasing consumption of high-fat foods combined with a lack of exercise is a major contributor to the burden of obesity in humans. Aerobic exercise such as running is known to provide metabolic benefits, but how the over-consumption of a high fat diet (HFD) and exercise interact is not well characterized at the molecular level. Here, we examined the plasma proteome in mice for the effects of aerobic exercise as both a treatment and as a preventative regime for animals on either HFD or a healthy control diet. This analysis detected large changes in the plasma proteome induced by the HFD, such as increased abundance of SERPINA7, ALDOB, and down-regulation of SERPINA1E, CFD (adipsin). Some of these changes were significantly reverted using exercise as a preventative measure, but not as a treatment regime. To determine if either the intensity, or duration, of exercise influenced the outcome, we compared high-intensity interval training (HIIT) and endurance running. Endurance running slightly out-performed HIIT exercise, but overall, both provided similar reversion in abundance of plasma proteins modulated by the high-fat diet including SERPINA7, APOE, SERPINA1E, and CFD. Finally, we compared the changes induced by over-consumption of HFD to previous data from mice fed an isocaloric high saturated fat (SFA) or polyunsaturated fat (PUFA) diet. This identified several common changes including increased APOC2 and APOE, but also highlighted changes specific for either over-consumption of HFD (ALDOB, SERPINA7, CFD), SFA-based diets (SERPINA1E), or PUFA-based diets (Haptoglobin - Hp). Together, these data highlight the importance of early intervention with exercise to revert HFD-induced phenotypes and suggest some of the molecular mechanisms leading to the changes in the plasma proteome generated by high fat diet consumption. Web-based interactive visualizations are provided for this dataset (larancelab.com/hfd-exercise), which give insight into diet and exercise phenotypic interactions on the plasma proteome.

scholarly journals Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Giuseppe Vassalli
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cellular Function ◽  
Stem Cell Marker ◽  
Cell Populations ◽  
Aldh Activity ◽  
Cellular Functions ◽  
Stem And Progenitor Cells

Aldehyde dehydrogenase (ALDH) is a superfamily of enzymes that detoxify a variety of endogenous and exogenous aldehydes and are required for the biosynthesis of retinoic acid (RA) and other molecular regulators of cellular function. Over the past decade, high ALDH activity has been increasingly used as a selectable marker for normal cell populations enriched in stem and progenitor cells, as well as for cell populations from cancer tissues enriched in tumor-initiating stem-like cells. Mounting evidence suggests that ALDH not only may be used as a marker for stem cells but also may well regulate cellular functions related to self-renewal, expansion, differentiation, and resistance to drugs and radiation. ALDH exerts its functional actions partly through RA biosynthesis, as all-trans RA reverses the functional effects of pharmacological inhibition or genetic suppression of ALDH activity in many cell types in vitro. There is substantial evidence to suggest that the role of ALDH as a stem cell marker comes down to the specific isoform(s) expressed in a particular tissue. Much emphasis has been placed on the ALDH1A1 and ALDH1A3 members of the ALDH1 family of cytosolic enzymes required for RA biosynthesis. ALDH1A1 and ALDH1A3 regulate cellular function in both normal stem cells and tumor-initiating stem-like cells, promoting tumor growth and resistance to drugs and radiation. An improved understanding of the molecular mechanisms by which ALDH regulates cellular function will likely open new avenues in many fields, especially in tissue regeneration and oncology.

Follicle dominance and ovarian asymmetry after luteectomy in rhesus monkeys

1982 ◽  
Vol 243 (4) ◽  
pp. E325-E331 ◽  
Author(s):  
A. L. Goodman ◽  
M. J. Koering ◽  
W. E. Nixon ◽  
R. F. Williams ◽  
G. D. Hodgen
Keyword(s):  
Rhesus Monkeys ◽  
Selection Process ◽  
Ovarian Cycle ◽  
Ovarian Activity ◽  
Dominant Follicle ◽  
Lh Surge ◽  
Morphological Asymmetry ◽  
Cynomolgus Macaques ◽  
Follicle Selection ◽  
Midluteal Phase

Previous work demonstrated that asymmetrical ovarian activity accompanies morphological asymmetry during the ovarian cycle in rhesus and cynomolgus macaques. This study was designed to determine whether functional ovarian asymmetry could be used to detect the upcoming dominant follicle (DF) even before it was grossly visible. Revealing a latent DF in this manner would permit a better estimate of the time when dominance of the follicle selected to ovulate is attained. To accomplish this, rhesus monkeys were luteectomized at midluteal phase to synchronize subsequent follicle growth, and 4 or 8 days later either the ipsilateral or contralateral ovary was removed. Unilateral ablation at day 4 (when no DF is grossly apparent) of either ovary produced symmetrical responses: the interval from luteectomy (CLX) to the next luteinizing hormone (LH) surge was extended by about 4 days in both groups (P less than 0.01), i.e., from about 12.5 days to 16.7 +/- 1.6 and 17.0 +/- 1.5 days (mean +/- SE). In contrast, hemiovariectomy at day 8 produced markedly divergent asymmetrical responses. Removal of the ipsilateral ovary 8 days after CLX did not affect the timing of the next LH surge (13.2 +/- 0.6 days), which ordinarily occurs about 12.5 days after CLX alone. However, ablation of the contralateral ovary (bearing the next DF) on day 8 extended the interval from CLX to the next LH surge from about 12.5 to 26.6 +/- 1.3 days. These findings indicate that, during the normal ovarian cycle when menses occurs 2--4 days after luteolysis, the follicle destined to ovulate becomes dominant between the 2nd and 6th day and that attainment of dominance signals the completion of a follicle selection process that begins or resumes promptly after luteolysis.

Sign in / Sign up

Export Citation Format

Share Document