VTechWorks Repository :: Browsing by Author "Cline, Mark A."

Browsing by Author "Cline, Mark A."

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AMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manner
Piekarski, Alissa; Nagarajan, Gurueswar; Ishola, Peter; Flees, Joshua; Greene, Elizabeth S.; Kuenzel, Wayne J.; Ohkubo, Takeshi; Maier, Helena; Bottje, Walter G.; Cline, Mark A.; Dridi, Sami (Frontiers, 2018-05-15)
Autophagy, a highly conserved intracellular self-digestion process, plays an integral role in maintaining cellular homeostasis. Although emerging evidence indicate that the endocrine system regulates autophagy in mammals, there is still a scarcity of information on autophagy in avian (non-mammalian) species. Here, we show that intracerebroventricular administration of leptin reduces feed intake, modulates the expression of feeding-related hypothalamic neuropeptides, activates leptin receptor and signal transducer and activator of transcription (Ob-Rb/STAT) pathway, and significantly increases the expression of autophagy-related proteins (Atg3, Atg5, Atg7, beclinl, and LC3B) in chicken hypothalamus, liver, and muscle. Similarly, leptin treatment activates Ob-Rb/STAT pathway and increased the expression of autophagy-related markers in chicken hypothalamic organotypic cultures, muscle (QM7) and hepatocyte (Sim-CEL) cell cultures as well as in Chinese Hamster Ovary (CHO-K1) cells-overexpressmg chicken Ob-Rb and STAT3. To define the downstream mediator(s) of leptin's effects on autophagy, we determined the role of the master energy sensor AMP-activated protein kinase (AMPK). Leptin treatment significantly increased the phosphorylated levels of AMPK alpha 1/2 at Thr172 site in chicken hypothalamus and liver, but not in muscle. Likewise, AMPK alpha 1/2 was activated by leptin in chicken hypothalamic organotypic culture and Sim-CEL, but not in QM7 cells. Blocking AMPK activity by compound C reverses the autophagy-inducing effect of leptin. Together, these findings indicate that AMPK mediates the effect of leptin on chicken autophagy in a tissue-specific manner.
Biomolecules Triggering Altered Food Intake during Pathogenic Challenge in Chicks
Tachibana, Tetsuya; Cline, Mark A. (Japan Poultry Science Association, 2023-04)
Food intake is regulated by several complicated synergistic mechanisms that are affected by a variety of internal and ex-ternal influences. Some of these factors include those that are released from pathogens such as bacteria, fungi, and viruses, and most of these factors are associated with suppression of the chick's food intake. Although chicks are well-known to decrease their food intake when they experience a pathogenic challenge, the mechanisms that mediate this type of satiety are poorly understood. One of the goals of our research group has been to better understand these mechanisms in chicks. We recently provided evidence that pathogen-associated molecular patterns, which are recognized by pattern-recognition receptors such as Toll-like receptors, likely contribute to satiety in chicks that are experiencing a pathogenic challenge. Additionally, we identified several inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor-like cytokine 1A, prostaglandins, and nitric oxide, that likely contribute to satiety during a pathogenic challenge. This review summarizes the current knowl-edge on pathogen-induced satiety in chicks mainly accumulated through our recent research. The research will give good information to improve the loss of production during infection in poultry production in the future.
Central mechanisms of prolactin-releasing peptides orexigenic effect in chickens
Wang, Guoqing (Virginia Tech, 2015-06-29)
Prolactin-releasing peptide (PrRP) is an endogenous hypothalamic neuropeptide that when exogenously injected increases food intake in chickens, but decreases it in rodents and goldfish. We designed three sets of experiments to elucidate the mechanisms of PrRP's orexigenic effect in chicks. In experiment one, food and water intake were evaluated in chicks after receiving intracerebroventricular (ICV) injection of the vehicle, 0.75, 3, 12, 47 or 188 pmol PrRP. The administration of 12 and 47 pmol PrRP increased food intake for up to 120 min after injection, and 188 pmol increased it for up to 180 min. The lowest effective dose was 3 pmol, which increased food intake for up to 60 min after injection. Water intake was not affected. To investigate the molecular mechanisms, c-Fos immunohistochemistry was performed and mRNA expression of some appetite-associated neurotransmitters was measured in chicks that received either vehicle or 188 pmol of PrRP. The rostral paraventricular nucleus (PVN) was activated which coincided with increased neuropeptide Y (NPY) mRNA expression in the whole hypothalamus. In experiment two, food and water intake were evaluated in chicks fed a high carbohydrate (HC), high fat (HF) or high protein (HP) diet after ICV injection of vehicle, 3 or 188 pmol PrRP. Chicks fed the HP diet increased food intake at a lower dose than chicks fed HF and HP diets after ICV PrRP injection. In addition, ICV injection of vehicle, 3 and 188 pmol PrRP were performed in chicks fed all three diets, and ICV PrRP injection induced preferential intake of the HP diet over HC and HF diets. The expression of some appetite-associated neuropeptides in the hypothalamus was also measured in chicks fed the HC, HF or HP diet after ICV injection of vehicle or 188 pmol PrRP. There was a diet effect on mRNA abundance of all appetite-associated genes measured (P < 0.05), with greater expression in chicks fed the HF or HP than HC diet. While neuropeptide Y (NPY) mRNA abundance was similar between vehicle and PrRP-injected chicks that consumed HP or HF diets, expression was greater (P < 0.05) in PrRP- than vehicle-injected chicks that consumed the HC. In experiment three, the orexigenic effect of PrRP was tested in chicks selected for low (LWS) and high (HWS) body weight after central administration of vehicle, 24, 94 and 375 pmol PrRP. The LWS chicks had a lower threshold and higher magnitude of food intake increase in response to PrRP injection. Results demonstrate that PrRP is a potent orexigenic factor in chickens and that effects are likely mediated through the hypothalamus. The orexigenic effect of PrRP was influenced by dietary macronutrient composition, and diet in turn influenced the food intake response to PrRP. These results may contribute to a novel understanding of appetite regulation.
Central Taurine Attenuates Hyperthermia and Isolation Stress Behaviors Augmented by Corticotropin-Releasing Factor with Modifying Brain Amino Acid Metabolism in Neonatal Chicks
Elhussiny, Mohamed Z.; Tran, Phuong V.; Tsuru, Yuriko; Haraguchi, Shogo; Gilbert, Elizabeth R.; Cline, Mark A.; Bungo, Takashi; Furuse, Mitsuhiro; Chowdhury, Vishwajit S. (MDPI, 2022-01-16)
The objective of this study was to determine the effects of centrally administered taurine on rectal temperature, behavioral responses and brain amino acid metabolism under isolation stress and the presence of co-injected corticotropin-releasing factor (CRF). Neonatal chicks were centrally injected with saline, 2.1 pmol of CRF, 2.5 μmol of taurine or both taurine and CRF. The results showed that CRF-induced hyperthermia was attenuated by co-injection with taurine. Taurine, alone or with CRF, significantly decreased the number of distress vocalizations and the time spent in active wakefulness, as well as increased the time spent in the sleeping posture, compared with the saline- and CRF-injected chicks. An amino acid chromatographic analysis revealed that diencephalic leucine, isoleucine, tyrosine, glutamate, asparagine, alanine, β-alanine, cystathionine and 3-methylhistidine were decreased in response to taurine alone or in combination with CRF. Central taurine, alone and when co-administered with CRF, decreased isoleucine, phenylalanine, tyrosine and cysteine, but increased glycine concentrations in the brainstem, compared with saline and CRF groups. The results collectively indicate that central taurine attenuated CRF-induced hyperthermia and stress behaviors in neonatal chicks, and the mechanism likely involves the repartitioning of amino acids to different metabolic pathways. In particular, brain leucine, isoleucine, cysteine, glutamate and glycine may be mobilized to cope with acute stressors.
Chickens from lines artificially selected for juvenile low and high body weight differ in glucose homeostasis and pancreas physiology
Sumners, Lindsay Hart (Virginia Tech, 2015-01-30)
Early pancreatectomy experiments performed in ducks and pigeons at the end of the 19th century revealed that avians, unlike mammals, do not display signs of diabetes. Relative to mammals, birds are considered hyperglycemic, displaying fasting blood glucose concentrations twice that of a normal human. While circulating levels of insulin are similar in avians and mammals, and structure and function of the insulin receptor are also conserved among vertebrate species, birds do not experience deleterious effects of chronic hyperglycemia as observed in mammals. Understanding avian glucose homeostasis, particularly in chickens, has both agricultural and biomedical implications. Improvement of feed efficiency and accelerated growth in poultry may come from a greater understanding of the physiological processes associated with glucose utilization in muscle and fat. The chicken has also recently been recognized as an attractive model for human diabetes, where there is a great need for preventative and therapeutic strategies. The link between type 2 diabetes and obesity, coupled with the inherent hyperglycemic nature of chickens, make chickens artificially selected for juvenile low (LWS) and high (HWS) body weight a favorable model for investigating glucose regulation and pancreas physiology. Oral glucose tolerance and insulin sensitivity tests revealed differences in threshold sensitivity to insulin and glucose clearance rate between the lines. Results from real-time PCR showed greater pancreatic mRNA expression of four glucose regulatory genes (preproinsulin, PPI; preproglucagon, PPG; glucose transporter 2, GLUT2; and pancreatic duodenal homeobox 1, Pdx1) in LWS, than HWS chickens. Histological analysis of pancreas revealed that HWS chickens have larger pancreatic islets, less pancreatic islet mass, and more pancreatic inflammation than LWS chickens, all of which presumably contribute to impaired glucose metabolism. In summary, results suggest that at selection age, there are differences in pancreas physiology that may explain the differences in glucose regulation between LWS and HWS. These data pave the way for future studies aimed at understanding the developmental regulation of endocrine pancreas function in chickens, as well as how aging affects homeostatic control of blood glucose in chickens.
Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue
Zhang, Shuai (Virginia Tech, 2013-12-12)
The ability to adapt fuel usage to nutrient availability is termed metabolic flexibility, and is influenced by activity of the pyruvate dehydrogenase complex (PDC). The Virginia lines of chickens are a unique model of anorexia and obesity that have resulted from 56 generations of artificial selection for high (HWS) or low (LWS) juvenile body weight. We hypothesized that hyperphagia and obesity in juvenile HWS chickens are associated with altered fatty acid oxidation efficiency and metabolic flexibility in tissues associated with energy sensing and storage, and relative cellular hypertrophy in white adipose tissue. Hypothalamus, liver, Pectoralis major, gastrocnemius, abdominal fat, clavicular fat and subcutaneous fat were collected from juvenile (56-65 day-old) HWS and LWS chickens for metabolic, gene expression and histological assays. The HWS chickens had reduced fatty acid oxidation efficiency in abdominal fat (P < 0.0001) and reduced rates of oxidation in abdominal fat and gastrocnemius (P < 0.0001) as compared to LWS. There was reduced citrate synthase activity in white adipose tissue (P < 0.0001) and greater metabolic inflexibility in skeletal muscle (P = 0.006) of HWS compared to LWS. Greater pyruvate dehydrogenase kinase 4 (PDK4) and forkhead box O1 (FoxO1) mRNA were found in skeletal muscle and white adipose tissue of 56-day-old HWS than LWS. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in all adipose tissue depots was greater (P < 0.05) in LWS than in HWS chickens. The HWS chickens had larger (P < 0.0001) and fewer (P < 0.0001) adipocytes per unit area than LWS. These results suggest that the HWS chickens have impaired metabolic flexibility and fatty acid oxidation efficiency due to an up-regulation of pyruvate dehydrogenase activity to accommodate the influx of acetyl CoA from fatty acid oxidation in skeletal muscle and white adipose tissue. These metabolic adaptations can be linked to differences in gene expression regulation and body composition between the lines. Adipocyte cellularity data are consistent with greater oxidative efficiency in the adipose tissue of LWS, because of the greater number of unfilled cells in all depots that were sampled. Results can be extrapolated to agricultural production in the understanding of factors regulating the amount of lipid deposition in chicken carcass fat. Results may also provide insight into eating disorders and the development of obesity.
Chronic stress and adipose tissue in the anorexic state: endocrine and epigenetic mechanisms
Xiao, Yang; Liu, Dongmin; Cline, Mark A.; Gilbert, Elizabeth R. (Taylor & Francis, 2020)
Although adipose tissue metabolism in obesity has been widely studied, there is limited research on the anorexic state, where the endocrine system is disrupted by reduced adipose tissue mass and there are depot-specific changes in adipocyte type and function. Stress exposure at different stages of life can alter the balance between energy intake and expenditure and thereby contribute to the pathogenesis of anorexia nervosa. This review integrates information from human clinical trials to describe endocrine, genetic and epigenetic aspects of adipose tissue physiology in the anorexic condition. Changes in the hypothalamus-pituitary-thyroid, -adrenal, and -gonadal axes and their relationships to appetite regulation and adipocyte function are discussed. Because of the role of stress in triggering or magnifying anorexia, and the dynamic but also persistent nature of environmentally-induced epigenetic modifications, epigenetics is likely the link between stress and long-term changes in the endocrine system that disrupt homoeostatic food intake and adipose tissue metabolism. Herein, we focus on the adipocyte and changes in its function, including alterations reinforced by endocrine disturbance and dysfunctional adipokine regulation. This information is critical because of the poor understanding of anorexic pathophysiology, due to the lack of suitable research models, and the complexity of genetic and environmental interactions.
Chronic stress, epigenetics, and adipose tissue metabolism in the obese state
Xiao, Yang; Liu, Dongmin; Cline, Mark A.; Gilbert, Elizabeth R. (2020-10-19)
In obesity, endocrine and metabolic perturbations, including those induced by chronic activation of the hypothalamus–pituitary–adrenal axis, are associated with the accumulation of adipose tissue and inflammation. Such changes are attributable to a combination of genetic and epigenetic factors that are influenced by the environment and exacerbated by chronic activation of the hypothalamus–pituitary–adrenal axis. Stress exposure at different life stages can alter adipose tissue metabolism directly through epigenetic modification or indirectly through the manipulation of hypothalamic appetite regulation, and thereby contribute to endocrine changes that further disrupt whole-body energy balance. This review synthesizes current knowledge, with an emphasis on human clinical trials, to describe metabolic changes in adipose tissue and associated endocrine, genetic and epigenetic changes in the obese state. In particular, we discuss epigenetic changes induced by stress exposure and their contribution to appetite and adipocyte dysfunction, which collectively promote the pathogenesis of obesity. Such knowledge is critical for providing future directions of metabolism research and targets for treating metabolic disorders.
Corticotrophin Releasing Hormone Modulation of Feed Intake, Gastric Motility, and Behavior in Low and High Body Weight Selected Lines of Chickens
Cline, Mark A. (Virginia Tech, 2005-05-04)
The effect of intracerebroventricular (ICV) injection of corticotrophin releasing hormone (CRH) and related compounds on appetite, behavior, and gastric motility in lines of chickens, one selected for low body weight (LWS) and the other high body weight (HWS), was determined. Nucleotide sequence and expression patterns of the CRHr2 receptor, involved in appetite regulation, were also determined. Some individuals of the LWS line are anorexics and many die simply from not eating while some individuals in the HWS line are compulsive eaters and exhibit obesity. CRH is a 41 residue peptide that initiates an organism's stress response and is a potent inhibitor of appetite. An ICV injection of CRH dose-dependently decreased feed intake in both lines but did not effect water intake. When CRH receptor antagonists were ICV injected an increase in feed intake in the LWS line but not in the HWS line was observed, however the appetite reducing effect of CRH was attenuated in the HWS line but not in the LWS line. The LWS line has higher concentration of corticosterone than does the HWS line. In both lines at all times treatment with CRH caused an increase in locomotion and no CRH-treated chicks from either line slept post injection. Chicks from the LWS line that were treated with CRH exhibited other anxiety related behaviors sooner than the HWS line. The LWS line showed a liner increase in crop emptying time as the dose of ICV CRH increased. The HWS line responded with a quadratic dose response to CRH treatment. Polymorphisms in the CRHr2 receptor were found in both lines in the same positions, thus we concluded these differences do not significantly contribute to body weight differences. However, differences detected in expression patterns between lines for the CRHr2 receptor may contribute to their different body weights. We conclude that differences in the CRH system, its concentrations and differential receptor action, of these two lines may be partly responsible for their altered body weight phenotype.
Dietary Flavonoids as Modulators of Lipid Metabolism in Poultry
Tan, Zhendong; Halter, Bailey; Liu, Dongmin; Gilbert, Elizabeth R.; Cline, Mark A. (Frontiers, 2022-04-25)
Flavonoids, naturally-occurring compounds with multiple phenolic structures, are the most widely distributed phytochemicals in the plant kingdom, and are mainly found in vegetables, fruits, grains, roots, herbs, and tea and red wine products. Flavonoids have health-promoting effects and are indispensable compounds in nutritional and pharmaceutical (i.e., nutraceutical) applications. Among the demonstrated bioactive effects of flavonoids are anti-oxidant, anti-inflammatory, and anti-microbial in a range of research models. Through dietary formulation strategies, numerous flavonoids provide the ability to support bird health while improving the nutritional quality of poultry meat and eggs by changing the profile of fatty acids and reducing cholesterol content. A number of such compounds have been shown to inhibit adipogenesis, and promote lipolysis and apoptosis in adipose tissue cells, and thereby have the potential to affect fat accretion in poultry at various ages and stages of production. Antioxidant and anti-inflammatory properties contribute to animal health by preventing free radical damage in tissues and ameliorating inflammation in adipose tissue, which are concerns in broiler breeders and laying hens. In this review, we summarize the progress in understanding the effects of dietary flavonoids on lipid metabolism and fat deposition in poultry, and discuss the associated physiological mechanisms.
Dietary macronutrient composition and exogenous neuropeptide Y affect feed intake in brioler chicks
Nelson, Laura Ashley (Virginia Tech, 2014-06-11)
Understanding the central nervous systems role in appetite regulation is crucial to cure the obesity epidemic, which is more prevalent than any disease in the United States. Central appetite regulators, known as neuropeptides, are pivotal in understanding appetite regulation. Neuropeptide Y (NPY), a 36 amino acid peptide, plays a major role in regulating the hunger signals from the brain. In all vertebrates studied, it is a strong orexigenic neurotransmitter located throughout multiple nuclei of the hypothalamus. Peripheral hormones associated with hunger are able to activate NPY neurons in the arcuate nucleus, which leads to a cascade of events that activate orexigenic neurons throughout the hypothalamus. Although extensive research has gone into understanding the role of NPY in appetite regulation, the effects of macronutrient composition of diets on NPY function have not been elucidated in non-mammalian species. This research investigates how food intake is affected by dietary macronutrient composition in broiler type chickens that are fed three varying macronutrient diets: high carbohydrate (22% CP, 3000kcal/kg) a broiler starter diet, high fat (60% ME from lard), high protein 30%CP). All diets were formulated to be isocaloric. When chicks are fed the high fat diet central NPY administration has a greater effect on feed intake compared to both the basal and high protein diet. Regardless of what diet the chick is fed from hatch, if they are switched to one of the other two diets post central administration of NPY the high fat diet stimulated feed intake for the longest duration. Although, NPY had the strongest orexigenic effect on chicks fed the high fat diet, in a choice diet situation broiler chicks chose the high protein diet, independent of central NPY administration.
Dietary Supplementation of Baicalein Affects Gene Expression in Broiler Adipose Tissue During the First Week Post-hatch
Xiao, Yang; Halter, Bailey; Boyer, Casey; Cline, Mark A.; Liu, Dongmin; Gilbert, Elizabeth R. (Frontiers, 2021-06-25)
Dietary supplementation of baicalein, a flavonoid, has anti-obesity effects in mammals and broiler chickens. The aim of this study was to determine the effect of dietary baicalein supplementation on broiler growth and adipose tissue and breast muscle deposition. Fifty Hubbard Cobb-500 day-of-hatch broiler chicks were assigned to a control starter diet or control diet supplemented with 125, 250, or 500 mg/kg baicalein and diets were fed for the first 6 days post-hatch. Body weight, average daily body weight gain, and average daily food intake were all reduced by 500 mg/kg baicalein. Breast muscle and subcutaneous and abdominal fat weights were also reduced in chicks that consumed the baicalein-supplemented diets. mRNAs for genes encoding factors involved in adipogenesis and fat storage, 1-acylglycerol-3-phosphate-O-acyltransferase 2, CCAAT/enhancer-binding protein b, perilipin-1, and sterol regulatory element-binding transcription factor 1, were more highly expressed in the adipose tissue of broilers supplemented with baicalein than the controls, independent of depot. Diacylglycerol acyltransferase and peroxisome proliferator-activated receptor gamma mRNAs, involved in triacylglycerol synthesis and adipogenesis, respectively, were greater in subcutaneous than abdominal fat, which may contribute to differences in expansion rates of these depots. Results demonstrate effects of dietary supplementation of baicalein on growth performance in broilers during the early post-hatch stage and molecular effects in major adipose tissue depots. The mild reduction in food intake coupled to slowed rate of breast muscle and adipose tissue accumulation may serve as a strategy to modulate broiler growth and body composition to prevent metabolic and skeletal disorders later in life.
Dietary Supplementation of Chinese Ginseng Prevents Obesity and Metabolic Syndrome in High-Fat Diet-Fed Mice
Li, Xiaoxiao; Luo, Jing; Babu, Pon Velayutham Anandh; Zhang, Wei; Gilbert, Elizabeth R.; Cline, Mark A.; McMillan, Ryan P.; Hulver, Matthew W.; Alkhalidy, Hana; Zhen, Wei; Zhang, Haiyan; Liu, Dongmin (Mary Ann Liebert, 2014-12-01)
Obesity and diabetes are growing health problems worldwide. In this study, dietary provision of Chinese ginseng (0.5 g/kg diet) prevented body weight gain in high-fat (HF) diet-fed mice. Dietary ginseng supplementation reduced body fat mass gain, improved glucose tolerance and whole body insulin sensitivity, and prevented hypertension in HF diet-induced obese mice. Ginseng consumption led to reduced concentrations of plasma insulin and leptin, but had no effect on plasma adiponectin levels in HF diet-fed mice. Body temperature was higher in mice fed the ginseng-supplemented diet but energy expenditure, respiration rate, and locomotive activity were not significantly altered. Dietary intake of ginseng increased fatty acid oxidation in the liver but not in skeletal muscle. Expression of several transcription factors associated with adipogenesis (C/EBP alpha and PPAR gamma) were decreased in the adipose tissue of HF diet-fed mice, effects that were mitigated in mice that consumed the HF diet supplemented with ginseng. Abundance of fatty acid synthase (FASN) mRNA was greater in the adipose tissue of mice that consumed the ginseng-supplemented HF diet as compared with control or un-supplemented HF diet-fed mice. Ginseng treatment had no effect on the expression of genes involved in the regulation of food intake in the hypothalamus. These data suggest that Chinese ginseng can potently prevent the development of obesity and insulin resistance in HF diet-fed mice.
Differential appetite regulation in lines of chickens selected for high and low juvenile body weight: the role of beta-MSH
Smith, Marissa L. (Virginia Tech, 2011-03-18)
Melanocortins play a key role in appetite regulation across species. One such melanocortin, beta-melanocyte stimulating hormone (beta-MSH) is receiving increasing attention for its anorexigenic effects. In chicks selected for low (LWS) and high (HWS) juvenile body weight, beta-MSH differentially decreased food intake and HWS chicks may be more sensitive to its effects. Both lines responded similarly to beta-MSH with decreased water intake. While whole blood glucose concentrations and ingestive and non-ingestive behaviors (sit, stand, preen, perch, deep rest, jumps, escape attempts, feed pecks, defecations, and total distance traveled) were not affected in either line, beta-MSH increased corticosterone in LWS chicks but not HWS chicks. However, despite the increase in corticosterone concentration in LWS, astressin, a corticotrophin releasing hormone (CRH) receptor antagonist, did not attenuate the effects of beta-MSH in either line suggesting that the altered stress response may not be acting via CRH receptors. When beta-MSH was co-administered with HS014, a highly selective antagonist for the melanocortin 4 receptor, only LWS responded with an attenuated response to beta-MSH suggesting that the differential response may in part be due to altered receptor affinity or binding resulting from the selection process. To investigate the roles of the hypothalamus and hindbrain in the differential food intake response, an experiment was designed where chicks were injected targeting either the lateral or 4th ventricle utilizing a novel freehand injection procedure. Chicks from both lines responded similarly to beta-MSH following both lateral and 4th ventricle injections. Together, these data suggest that alterations in the b-melanocortinergic appetite regulation system may be in part responsible for the differential body weights of the LWS and HWS lines. [Adaptations of chapters II, III, and IV have been published in Neuroscience Letters, Journal of Neuroendocrinology, and Behavioural Brain Research, respectively]
Early-Life Stress Induced Epigenetic Changes of Corticotropin-Releasing Factor Gene in Anorexic Low Body Weight–Selected Chicks
Xiao, Yang; Wang, Jinxin; Siegel, Paul B.; Cline, Mark A.; Gilbert, Elizabeth R. (MDPI, 2020-04-27)
The expression of neuropeptide Y (NPY) in the arcuate nucleus (ARC) and corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN) were increased when low body weight–selected (LWS) line chicks, which are predisposed to anorexia, were subjected to a combination of nutritional and thermal stressors at hatch. We hypothesized that such changes resulted from epigenetic modifications. We determined global DNA methylation, DNA methyltransferase (DNMT) activity, and methylation near the promoter regions of NPY and CRF, in the hypothalamus of LWS chicks on day 5 post-hatch. Stress exposure at hatch induced global hypermethylation and increased DNMT activity in the ARC but not PVN. In the PVN of stressed LWS chicks, there was decreased methylation of a CpG site located at the core binding domain of methyl cytosine binding domain protein 2 (MBD2), near the CRF gene promoter. We then demonstrated that this was associated with disrupted binding of MBD2. There was also reduced utilization of yolk reserves and lean and fat masses in chicks that were stress-exposed. These findings provide novel insights on molecular mechanisms through which stressful events induce or intensify anorexia in predisposed individuals and a novel molecular target for further studies.
Effects of dietary macronutrient composition and exogenous neuropeptide Y on adipose tissue development in broiler chicks
Wang, Guoqing (Virginia Tech, 2018-06-11)
The objective of this dissertation research was to investigate the effect of dietary macronutrient composition on neuropeptide Y (NPY)-mediated regulation of adipose tissue physiology in broiler chickens during the early post-hatch period. A high-carbohydrate (HC), high-fat (HF) or high-protein (HP) diet was fed to broiler chicks in all experiments and various facets of physiology were evaluated at day 4 post-hatch, including diet-, fasting-, and neuropeptide Y-induced effects on gene expression, cellular morphology, and lipid metabolism. Experiment 1 was designed to study the effects of diet on molecular changes in different adipose tissue depots (subcutaneous, clavicular and abdominal) after 3 hours of fasting and 1 hour of refeeding. Adipose tissue weights were decreased in chicks that consumed the HP diet, whereas adipocyte diameter was increased in response to the HF diet. There was greater expression of mRNAs encoding fatty acid binding protein 4 (FABP4) and monoglyceride lipase in chicks fed the HC and HF diets than the HP diet in all three adipose tissue depots. Fasting increased plasma non-esterified fatty acid concentrations in chicks fed the HC and HP diets. Results suggest that the heavier fat depots and larger adipocytes in chicks fed the HF diet are explained by greater rates of hypertrophy, whereas the HP diet led to a decrease in adipose tissue deposition, likely as a result of decreased rates of adipogenesis. Experiments 2 and 3 were designed to investigate how dietary macronutrient composition affects the effect of centrally or peripherally administered NPY, respectively, on lipid metabolism-associated factor mRNAs in adipose tissue. In experiment 2, vehicle or 0.2 nmol of NPY was injected intracerebroventricularly (ICV) and abdominal and subcutaneous fat samples were collected at 1 hour post-injection. In the subcutaneous fat, ICV NPY injection decreased peroxisome proliferator-activated receptor gamma (PPAR gamma) and sterol regulatory element-binding transcription factor 1 (SREBP1) mRNAs in chicks fed the HF diet, whereas there was an increase in SREBP1 expression in chicks fed the HF diet after NPY injection. Expression of PPAR gamma and FABP4 mRNAs increased in the abdominal fat of HF diet-fed chicks after NPY injection. Thus, HF diet consumption may have enhanced the sensitivity of chick adipose tissue to the effect of centrally-injected NPY on gene expression of adipogenesis-associated factors. In experiment 3, vehicle, 60, or 120 micrograms/kg BW of NPY was injected intraperitoneally (IP), and subcutaneous, clavicular, and abdominal fat was collected at 1 and 3 hours post-injection. Food intake and plasma NEFA concentrations were not different among chicks fed the HC, HF or HP diet after IP NPY injection, indicating that the effects of NPY on adipogenesis were independent of secondary effects due to altered energy intake. In response to the lower dose of NPY, the expression of NPY receptor sub-type 2 mRNA was increased at 1 hour post-injection in the subcutaneous fat of chicks fed the HP diet, whereas there was less 1-acylglycerol-3-phosphate O-acyltransferase 2 mRNA in the subcutaneous fat of chicks fed the HC diet. The higher dose of NPY was associated with greater AGPAT2 mRNA in the clavicular fat of chicks that consumed the HP diet and less CCAAT/enhancer-binding protein alpha in the abdominal fat of chicks that were provided the HF diet. However, there was also a decrease in the expression of some of these factors, although mechanisms are unclear. In conclusion, dietary macronutrient composition influenced the response of adipose tissue to the adipogenic effects of NPY and metabolic effects of short-term fasting and refeeding during the first week post-hatch. Collectively, this research may provide insights on understanding NPY's effects on the development of adipose tissue during the early life period and mechanisms underlying diet-dependent and depot-dependent differences in adipose tissue physiology across species.
The effects of dietary macronutrient composition on lipid metabolismassociated factor gene expression in the adipose tissue of chickens are influenced by fasting and refeeding
Wang, Guoqing; McConn, Betty R.; Liu, Dongmin; Cline, Mark A.; Gilbert, Elizabeth R. (BMC, 2017-05-10)
Background: Broiler chickens are compulsive feeders that become obese as juveniles and are thus a unique model for metabolic disorders in humans. However, little is known about the relationship between dietary composition, fasting and refeeding and adipose tissue physiology in chicks. Our objective was to determine how dietary macronutrient composition and fasting and refeeding affect chick adipose physiology during the early post-hatch period. Methods: Chicks were fed one of three isocaloric diets after hatch: high-carbohydrate (HC; control), high-fat (HF; 30% of ME from soybean oil) or high-protein (HP; 25% vs. 22% crude protein). At 4 days post-hatch, chicks were fed (continuous ad libitum access to food), fasted (3 h food withdrawal), or refed (fasted for 3 h and refed for 1 h). Subcutaneous, clavicular, and abdominal adipose tissue was collected for histological analysis and to measure gene expression, and plasma to measure non-esterified fatty acid (NEFA) concentrations (n = 6–10 per group). Results: Adipose tissue weights were reduced in chicks that were fed the HP diet and adipocyte diameter was greater in the adipose tissue of chicks that ate the HF diet. Consumption of diets differing in protein and fat content also affected gene expression; mRNAs encoding fatty acid binding protein 4 and a lipolytic enzyme, monoglyceride lipase, were greater in chicks fed the HC and HF than HP diet in all three adipose tissue depots. Fasting influenced gene expression in a depot-dependent manner, where most fasting and refeeding-induced changes were observed in the clavicular fat of chicks that consumed the HC diet. Fasting increased plasma NEFA concentrations in chicks fed the HC and HP diets. Conclusions: The decreased adipose tissue deposition in chicks fed the HP diet is likely explained by decreased rates of adipogenesis. Consumption of the HF diet was associated with greater adipose tissue deposition and larger adipocytes, likely as a result of greater rates of adipocyte hypertrophy. The depot-dependent effects of diet and fasting on gene expression may help explain mechanisms underlying metabolic distinctions among subcutaneous and visceral fat depots in humans.
Effects of exogenous and endogenous factors on appetite regulation in broiler chicks and Japanese quail
Halter, Bailey Anne (Virginia Tech, 2021-06-03)
Understanding how appetite is regulated, via exogenous or endogenous factors, is essential to animal agriculture in order to maximize production capabilities, as well as in human medicine to generate ways to treat conditions such as eating disorders or obesity. The aim of this thesis was to evaluate the effects of ferulic acid (FA), an exogenous factor found within plant cells, and oxyntomodulin (OXM), an endogenous hormone generated in the gastrointestinal tract, on food intake in avian models, as well as elucidate the hypothalamic mechanisms responsible. In broiler chicks (Gallus gallus), FA administered peripherally (IP) resulted in a transient yet potent reduction of food intake. A behavior analysis revealed that FA-treated chicks defecated fewer times than control birds. Within the arcuate nucleus (ARC) there was an increase in c-Fos immunoreactivity, indicating neuronal activation, in FA-treated chicks. Within the hypothalamus, there was a decrease in mRNA abundance of galanin, ghrelin, melanocortin receptor 3, and pro-opiomelanocortin (POMC), however within the ARC there was a decrease in POMC and an increase in c-Fos mRNA after FA treatment. OXM, a proglucagon-derived peptide produced in the gastrointestinal tract, administered intracerebroventricularly (ICV) or IP in Japanese quail (Coturnix japonica), resulted in a decrease in food intake for 3 hours post-injection. There was an increase in c-Fos immunoreactivity within the ARC as well as the dorsomedial nucleus (DMN) in quail ICV injected with OXM. In conclusion, these novel data provide insights on the similarities and differences between factors that can affect appetite regulation via anorexigenic effects.
Efficacy of Synthetic Gonadotropin Releasing Hormone Analogs for Control of Ovulation During Estrus Synchronization Protocols
Cline, Mark A. (Virginia Tech, 2002-01-30)
Two experiments were conducted to determine efficacy of GnRH analogs, Cystorelin (CYS, gonadorelin diacetate tytrahydrate) and Factrel (FAC, gonadorelin hydrochloride), for use in beef timed AI synchronization. In Experiment one 342 beef cows from 7 herds were assigned CYS or FAC treatment as part of the Ovsynch protocol (GnRH d 0 and 9, Lutalyse d 7). Cattle treated with FAC had greater tendency (P=.09) to be pregnant at d 45. One individual herd demonstrated FAC-treated cows had more pregnancies at day 45. In Experiment two, 18 beef cows received either CYS or FAC as part of the Ovsynch protocol, intensive blood samples, from time -30 to 525 min post GnRH, were collected at each GnRH injection. Ultrasounds were conducted daily over the course of the protocol. A treatment by phase interaction (P=.03) was found for the time to maximum LH concentration, where CYS-treated follicular cows had a shorter interval than did FAC treated follicular or luteal cows. The duration of detectable LH response showed a treatment by phase interaction (P = .02) where follicular and luteal CYS-treated cows had shorter interval than follicular or luteal FAC-treated cows. The variables maximum LH concentration, and area under LH curve did not differ. Cows treated with CYS had more (P=.02) non-dominant follicles. In Experiment three, 16 ewes randomly received either CYS, FAT or Fertagyl (FER; gonadorelin diacetaate tytrahydrate), and FAT's induced LH maximum concentration occurred sooner (P=.02) than CYS. We conclude that either product may be used in beef cows without compromising fertility.
Epigenetic modifiers identified as regulators of food intake in a unique hypophagic chicken model
Cao, Chang; Siegel, Paul B.; Gilbert, Elizabeth R.; Cline, Mark A. (Elsevier, 2022-06)
DNA methylation is an epigenetic modification that influences gene transcription; however, the effects of methylation-influencing chemicals on appetite are unknown. We evaluated the effects of single administration of a methyl donor, S-Adenosylmethionine (SAM), or methylation inhibitor, 5-Azacytidine (AZA), on immediate and later-age food intake in an anorexic chick model. The doses of intracerebroventricularlyinjected SAM were 0 (vehicle), 0.1, 1, and 10 mu g, and of AZA were 0 (vehicle), 1, 5, and 25 mu g. When injected on day 5 posthatch, there was no effect of SAM on food intake in either fed or fasted chicks, whereas AZA increased food consumption in the fasted state but decreased it in fed chicks. We then performed a single injection (same doses) at hatch and measured food intake on day 5 in response to neuropeptide Y (NPY; 0.2 mu g) injection. Irrespective of NPY, chicks injected with 1 mu g of SAM ate more than others on day 5. In contrast, chicks injected with AZA (5 and 25 mu g doses) consumed less on day 5. In conclusion, we identified DNA methylation-regulating chemicals as regulators of food intake. AZA but not SAM affected food intake in the short-term, feeding state dependently. Later, both chemicals injected on the day of hatch were associated with food intake changes at a later age, suggesting that feeding pathways might be altered through changes in methylation. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of The Animal Consortium. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Browsing by Author "Cline, Mark A."

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