37 results on '"Nicholas, Lisa"'
Search Results
2. Using Potentially Preventable Severe Maternal Morbidity to Monitor Hospital Performance
- Author
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Fridman, Moshe, Korst, Lisa M., Reynen, David J., Nicholas, Lisa A., Greene, Naomi, Saeb, Samia, Troyan, Jennifer L., and Gregory, Kimberly D.
- Published
- 2023
- Full Text
- View/download PDF
3. Severe Maternal Morbidity in California Hospitals: Performance Based on a Validated Multivariable Prediction Model
- Author
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Fridman, Moshe, Korst, Lisa M., Reynen, David J., Nicholas, Lisa A., Greene, Naomi, Saeb, Samia, Troyan, Jennifer L., and Gregory, Kimberly D.
- Published
- 2021
- Full Text
- View/download PDF
4. Early life programming in mice by maternal overnutrition : mechanistic insights and interventional approaches
- Author
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Nicholas, Lisa M. and Ozanne, Susan E.
- Published
- 2019
5. A scoping review of severe maternal morbidity: describing risk factors and methodological approaches to inform population-based surveillance
- Author
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Korst, Lisa M., Gregory, Kimberly D., Nicholas, Lisa A., Saeb, Samia, Reynen, David J., Troyan, Jennifer L., Greene, Naomi, and Fridman, Moshe
- Published
- 2021
- Full Text
- View/download PDF
6. Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice
- Author
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Nicholas, Lisa M., Nagao, Mototsugu, Kusinski, Laura C., Fernandez-Twinn, Denise S., Eliasson, Lena, and Ozanne, Susan E.
- Published
- 2020
- Full Text
- View/download PDF
7. Effects of a bitter substance, denatonium benzoate, on pancreatic hormone secretion.
- Author
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Weikun Huang, O'Hara, Stephanie E., Cong Xie, Ning Liu, Rayner, Christopher K., Nicholas, Lisa M., and Tongzhi Wu
- Subjects
ENTEROENDOCRINE cells ,PANCREATIC secretions ,BITTERNESS (Taste) ,TASTE receptors ,ISLANDS of Langerhans ,GASTROINTESTINAL hormones ,INSULIN receptors - Abstract
There is increasing evidence linking bitter taste receptor (BTR) signaling to gut hormone secretion and glucose homeostasis. However, its effect on islet hormone secretion has been poorly characterized. This study investigated the effect of the bitter substance, denatonium benzoate (DB), on hormone secretion from mouse pancreatic islets and INS-1 832/13 cells. DB (0.5-1 mM) augmented insulin secretion at both 2.8 mM and 16.7 mM glucose. This effect was no longer present at 5 mM DB likely due to the greater levels of cellular apoptosis. DB-stimulated insulin secretion involved closure of the KATP channel, activation of T2R signaling in beta-cells, and intraislet glucagon-like peptide-1 (GLP-1) release. DB also enhanced glucagon and somatostatin secretion, but the underlying mechanism was less clear. Together, this study demonstrates that the bitter substance, DB, is a strong potentiator of islet hormone secretion independent of glucose. This observation highlights the potential for widespread off-target effects associated with the clinical use of bitter-tasting substances. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. Mitochondrial transcription factor B2 is essential for mitochondrial and cellular function in pancreatic β-cells
- Author
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Nicholas, Lisa M., Valtat, Bérengère, Medina, Anya, Andersson, Lotta, Abels, Mia, Mollet, Inês G., Jain, Deepak, Eliasson, Lena, Wierup, Nils, Fex, Malin, and Mulder, Hindrik
- Published
- 2017
- Full Text
- View/download PDF
9. Interpregnancy Interval and Childbirth Outcomes in California, 2007-2009
- Author
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Cofer, Flojaune Griffin, Fridman, Moshe, Lawton, Elizabeth, Korst, Lisa M., Nicholas, Lisa, and Gregory, Kimberly D.
- Subjects
Infants -- Health aspects ,Delivery (Childbirth) -- Health aspects ,Pregnancy -- Complications and side effects -- Patient outcomes ,Gynecologic and obstetric hospitals -- Management ,Company business management ,Health care industry - Abstract
Objectives The goals of interconception care are to optimize women's health and encourage adequate spacing between pregnancies. Our study calculated trends in interpregnancy interval (IPI) patterns and measured the association of differing intervals with birth outcomes in California. Methods Women with 'non-first birth' deliveries in California hospitals from 2007 to 2009 were identified in a linked birth certificate and patient discharge dataset and divided into three IPI birth categories:, Author(s): Flojaune Griffin Cofer[sup.1] , Moshe Fridman[sup.2] , Elizabeth Lawton[sup.1] , Lisa M. Korst[sup.3] , Lisa Nicholas[sup.5] , Kimberly D. Gregory[sup.4] [sup.5] [sup.6] Author Affiliations: (1) Maternal, Child and Adolescent [...]
- Published
- 2016
- Full Text
- View/download PDF
10. Molecular mechanisms underlying adverse effects of dexamethasone and betamethasone in the developing cardiovascular system.
- Author
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Garrud, Tessa A. C., Teulings, Noor E. W. D., Niu, Youguo, Skeffington, Katie L., Beck, Christian, Itani, Nozomi, Conlon, Fiona G., Botting, Kimberley J., Nicholas, Lisa M., Tong, Wen, Derks, Jan B., Ozanne, Susan E., and Giussani, Dino A.
- Published
- 2023
- Full Text
- View/download PDF
11. Loss of TFB1M results in mitochondrial dysfunction that leads to impaired insulin secretion and diabetes
- Author
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Sharoyko, Vladimir V., Abels, Mia, Sun, Jiangming, Nicholas, Lisa M., Mollet, Ines Guerra, Stamenkovic, Jelena A., Göhring, Isabel, Malmgren, Siri, Storm, Petter, Fadista, João, Spégel, Peter, Metodiev, Metodi D., Larsson, Nils-Göran, Eliasson, Lena, Wierup, Nils, and Mulder, Hindrik
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- 2014
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- View/download PDF
12. Dietitian–general practitioner interface: a pilot study on what influences the provision of effective nutrition management
- Author
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Nicholas, Lisa G, Pond, C Dimity, and Roberts, David CK
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- 2003
- Full Text
- View/download PDF
13. Isolating adverse effects of glucocorticoids on the embryonic cardiovascular system.
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Teulings, Noor E. W. D., Garrud, Tessa A. C., Niu, Youguo, Skeffington, Katie L., Beck, Christian, Itani, Nozomi, Conlon, Fiona G., Botting, Kimberley J., Nicholas, Lisa M., Ashmore, Thomas J., Blackmore, Heather L., Tong, Wen, Camm, Emily J., Derks, Jan B., Logan, Angela, Murphy, Michael P., Ozanne, Susan E., and Giussani, Dino A.
- Published
- 2020
- Full Text
- View/download PDF
14. Unleashing the power of brand marketing in consumer banking.
- Author
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Nicholas, Lisa
- Subjects
RETAIL banking ,BRAND equity ,BRANDING (Marketing) ,BANK customers ,BANK marketing - Abstract
How to balance short-term and long-term investments. The pressure to deliver immediate results has led many marketers to focus more on short-term activation strategies and less on brand building. Balancing short-term activation with long-term brand investment is crucial for lasting success. Bank marketers must start depositing in customers' emotional piggy banks through always-on brand messaging. A recent study conducted by [ABSTRACT FROM AUTHOR]
- Published
- 2023
15. Maternal Obesity and the Early Origins of Childhood Obesity: Weighing Up the Benefits and Costs of Maternal Weight Loss in the Periconceptional Period for the Offspring
- Author
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Zhang, Song, Rattanatray, Leewen, Morrison, Janna L., Nicholas, Lisa M., Lie, Shervi, and McMillen, I. Caroline
- Subjects
Article Subject - Abstract
There is a need to understand the separate or interdependent contributions of maternal prepregnancy BMI, gestational weight gain, glycaemic control, and macronutrient intake on the metabolic outcomes for the offspring. Experimental studies highlight that there may be separate influences of maternal obesity during the periconceptional period and late gestation on the adiposity of the offspring. While a period of dietary restriction in obese mothers may ablate the programming of obesity, it is associated with an activation of the stress axis in the offspring. Thus, maternal obesity may result in epigenetic changes which predict the need for efficient fat storage in postnatal life, while maternal weight loss may lead to epigenetic changes which predict later adversity. Thus, development of dietary interventions for obese mothers during the periconceptional period requires a greater evidence base which allows the effective weighing up of the metabolic benefits and costs for the offspring.
- Published
- 2011
- Full Text
- View/download PDF
16. Gene expression allelic imbalance in ovine brown adipose tissue impacts energy homeostasis.
- Author
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Ghazanfar, Shila, Vuocolo, Tony, Morrison, Janna L., Nicholas, Lisa M., McMillen, Isabella C., Yang, Jean Y. H., Buckley, Michael J., and Tellam, Ross L.
- Subjects
GENE expression ,DNA ,GENETIC transcription ,PROTEINS ,AGRICULTURAL productivity - Abstract
Heritable trait variation within a population of organisms is largely governed by DNA variations that impact gene transcription and protein function. Identifying genetic variants that affect complex functional traits is a primary aim of population genetics studies, especially in the context of human disease and agricultural production traits. The identification of alleles directly altering mRNA expression and thereby biological function is challenging due to difficulty in isolating direct effects of cis-acting genetic variations from indirect trans-acting genetic effects. Allele specific gene expression or allelic imbalance in gene expression (AI) occurring at heterozygous loci provides an opportunity to identify genes directly impacted by cis-acting genetic variants as indirect trans-acting effects equally impact the expression of both alleles. However, the identification of genes showing AI in the context of the expression of all genes remains a challenge due to a variety of technical and statistical issues. The current study focuses on the discovery of genes showing AI using single nucleotide polymorphisms as allelic reporters. By developing a computational and statistical process that addressed multiple analytical challenges, we ranked 5,809 genes for evidence of AI using RNA-Seq data derived from brown adipose tissue samples from a cohort of late gestation fetal lambs and then identified a conservative subgroup of 1,293 genes. Thus, AI was extensive, representing approximately 25% of the tested genes. Genes associated with AI were enriched for multiple Gene Ontology (GO) terms relating to lipid metabolism, mitochondrial function and the extracellular matrix. These functions suggest that cis-acting genetic variations causing AI in the population are preferentially impacting genes involved in energy homeostasis and tissue remodelling. These functions may contribute to production traits likely to be under genetic selection in the population. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
17. Glycogen metabolism in the glucose-sensing and supply-driven β-cell.
- Author
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Andersson, Lotta E., Nicholas, Lisa M., Filipsson, Karin, Sun, Jiangming, Medina, Anya, Al-Majdoub, Mahmoud, Fex, Malin, Mulder, Hindrik, and Spégel, Peter
- Subjects
- *
GLYCOGEN synthases , *INSULIN , *ISLANDS of Langerhans , *GLYCOGENOLYSIS , *LABORATORY rodents - Abstract
Glycogen metabolism in β-cells may affect downstream metabolic pathways controlling insulin release. We examined glycogen metabolism in human islets and in the rodent-derived INS-1 832/13 β-cells and found them to express the same isoforms of key enzymes required for glycogen metabolism. Our findings indicate that glycogenesis is insulin-independent but influenced by extracellular glucose concentrations. Levels of glycogen synthase decrease with increasing glucose concentrations, paralleling accumulation of glycogen. We did not find cAMP-elicited glycogenolysis and insulin secretion to be causally related. In conclusion, our results reveal regulated glycogen metabolism in human islets and insulin-secreting cells. Whether glycogen metabolism affects insulin secretion under physiological conditions remains to be determined. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
18. Data-driven insights can improve your acquisition strategies.
- Author
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Nicholas, Lisa
- Subjects
CONSUMER behavior ,CONSUMER preferences ,CUSTOMER retention ,CONSUMERS ,MARKETING strategy ,COOKIES (Computer science) ,FINANCIAL institutions - Abstract
By leveraging first-party and third-party data, financial institutions can gain a more complete and more accurate picture of their customers. In today's data-driven economy, understanding and managing consumer data has become a critical aspect of successful marketing strategies. The elimination of third-party cookie tracking has financial services marketers increasingly reliant on their first-party customer data to gain insights into consumer behavior, preferences and needs and to develop targeted campaigns that maximize acquisition and retention. However, while [ABSTRACT FROM AUTHOR]
- Published
- 2023
19. Maternal obesity or weight loss around conception impacts hepatic fatty acid metabolism in the offspring.
- Author
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Nicholas, Lisa M., Rattanatray, Leewen, Morrison, Janna L., Kleemann, David O., Walker, Simon K., Zhang, Song, MacLaughlin, Severence, and McMillen, I. Caroline
- Subjects
OBESITY ,LIPID metabolism ,LIVER diseases ,FATTY liver ,FATTY acids - Abstract
Objective To determine the impact of maternal obesity or weight loss during the periconceptional period on programming of lipid metabolism in the liver of the offspring. Methods An embryo transfer model was used to investigate the effects of exposure to either maternal obesity and/or weight loss before and for 1-week post-conception on the abundance of key molecules regulating hepatic fatty acid oxidation and lipid synthesis in the 4-month-old lamb. Results Periconceptional maternal obesity resulted in decreased hepatic PPARα, PGC1α and GCN5 abundance and increased hepatic SIRT1 and AMPKα1, AMPKα2 and SREBP1 abundance in the offspring. Maternal weight loss in obese ewes did not ablate all of these effects of maternal obesity on hepatic metabolism in the lamb. Weight loss in normal weight ewes also resulted in decreased hepatic PGC1α and GCN5 and increased AMPKα2 abundance in the offspring. Conclusions Exposure of the oocyte/embryo to either maternal obesity or weight loss during the periconceptional period has long term consequences for hepatic lipid metabolism. These findings highlight the sensitivity of the early embryo to maternal nutrition and the need for dietary interventions which maximize metabolic benefits and minimize metabolic costs for the next generation. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
20. Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring.
- Author
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Nicholas, Lisa M., Rattanatray, Leewen, MacLaughlin, Severence M., Ozanne, Susan E., Kleemann, Dave O., Walker, Simon K., Morrison, Janna L., Song Zhang, Muhlhäusler, Beverley S., Martin-Gronert, Malgorzata S., and McMillen, Isabella C.
- Subjects
- *
INSULIN research , *OBESITY in animals , *GLUCONEOGENESIS , *SHEEP as laboratory animals , *MICRORNA - Abstract
Our aim was to determine the effect of exposure to maternal obesity or to maternal weight loss around conception on the programming of hepatic insulin signaling in the offspring. We used an embryo transfer model in sheep to investigate the effects of exposure to either maternal obesity or to weight loss in normal and obese mothers preceding and for 1 wk after conception on the expression of hepatic insulin-signaling and gluconeogenic factors and key miRNAs involved in insulin signaling in the offspring. We found that exposure to maternal obesity resulted in increased hepatic miR-29b (P<0.05), miR-103 (P<0.01), and miR-107 (P<0.05) expression, a decrease in IR (P<0.05), phopsho-Akt (P<0.01), and phospho-FoxO1 (P<0.01) abundance, and a paradoxical decrease in 11βHSD 1 (P< 0.05), PEPCK-C (P<0.01), and PEPCK-M (P<0.05) expression in lambs. These changes were ablated by a period of moderate dietary restriction imposed during the periconceptional period. Maternal dietary restriction alone also resulted in decreased abundance of a separate subset of hepatic insulin-signaling molecules, namely, IRS1 (P<0.05), PDK1 (P<0.01), phospho-PDK1 (P<0.05), and aPKCζ (P<0.05) and in decreased PEPCK-C (P<0.01) and G6Pase (P<0.01) expression in the lamb. Our findings highlight the sensitivity of the epigenome to maternal nutrition around conception and the need for dietary interventions that maximize metabolic benefits and minimize metabolic costs for the next generation. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
21. Maternal Obesity and the Early Origins of Childhood Obesity: Weighing Up the Benefits and Costs of Maternal Weight Loss in the Periconceptional Period for the Offspring.
- Author
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Song Zhang, Rattanatray, Leewen, Morrison, Janna L., Nicholas, Lisa M., Lie, Shervi, and McMillen, I. Caroline
- Subjects
MATERNAL health ,BODY mass index ,WEIGHT gain in pregnancy ,OBESITY in women ,CHILDHOOD obesity ,EPIGENETICS - Abstract
There is a need to understand the separate or interdependent contributions of maternal prepregnancy BMI, gestational weight gain, glycaemic control, and macronutrient intake on the metabolic outcomes for the offspring. Experimental studies highlight that there may be separate influences of maternal obesity during the periconceptional period and late gestation on the adiposity of the offspring. While a period of dietary restriction in obese mothers may ablate the programming of obesity, it is associated with an activation of the stress axis in the offspring. Thus, maternal obesity may result in epigenetic changes which predict the need for efficient fat storage in postnatal life, while maternal weight loss may lead to epigenetic changes which predict later adversity. Thus, development of dietary interventions for obese mothers during the periconceptional period requires a greater evidence base which allows the effective weighing up of the metabolic benefits and costs for the offspring. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
22. The role of the general practitioner and the dietitian in patient nutrition management.
- Author
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Nicholas, Lisa, Roberts, David CK, and Pond, Dimity
- Subjects
- *
NUTRITION counseling , *PHYSICIANS , *DIETITIANS , *MEDICAL care , *PRIMARY care , *DISEASES - Abstract
There is mounting evidence that nutrition plays an important role in the aetiology and management of many diseases affecting Australians. Nutrition counseling provides a strategy for not only reducing patient suffering, but also for reducing the health care costs associated with these illnesses. At the forefront of providing nutrition counseling to Australians are General Practitioners (GPs) and Dietitians. Australian data shows that GPs encounter many patients with the chronic diseases that have nutrition in their aetiology and management. Although this presents opportunities to provide nutrition counseling, overseas literature suggests that often nutrition counseling opportunities are not taken up. At present, there is little evidence to support whether this problem exists in Australia, or the magnitude of the problem. Whilst evidence suggests there are barriers for GPs in providing nutrition counseling, there is conflicting evidence on how these influence the GP's decision to provide such counseling. Overseas studies have also identified barriers for GPs to refer to dietitians to provide nutrition counseling, however there is no evidence to identify whether these barriers exist in Australia. Whilst various strategies have been implemented to aid in the provision of effective nutrition management to the Australian public, there is little evidence on the efficacy of these. Research is needed in the above areas if effective patient nutrition management is to be implemented in Australia. [ABSTRACT FROM AUTHOR]
- Published
- 2003
23. Understanding the Long-Lasting Effects of Fetal Nutrient Restriction versus Exposure to an Obesogenic Diet on Islet-Cell Mass and Function.
- Author
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O'Hara, Stephanie E., Gembus, Kelly M., and Nicholas, Lisa M.
- Subjects
MALNUTRITION ,ISLANDS of Langerhans ,TYPE 2 diabetes ,PHENOTYPIC plasticity ,PHENOTYPES ,DIET - Abstract
Early life represents a window of phenotypic plasticity. Thus, exposure of the developing fetus to a compromised nutritional environment can have long term consequences for their health. Indeed, undernutrition or maternal intake of an obesogenic diet during pregnancy leads to a heightened risk of type 2 diabetes (T2D) and obesity in her offspring in adult life. Given that abnormalities in beta-cell function are crucial in delineating the risk of T2D, studies have investigated the impact of these exposures on islet morphology and beta-cell function in the offspring in a bid to understand why they are more at risk of T2D. Interestingly, despite the contrasting maternal metabolic phenotype and, therefore, intrauterine environment associated with undernutrition versus high-fat feeding, there are a number of similarities in the genes/biological pathways that are disrupted in offspring islets leading to changes in function. Looking to the future, it will be important to define the exact mechanisms involved in mediating changes in the gene expression landscape in islet cells to determine whether the road to T2D development is the same or different in those exposed to different ends of the nutritional spectrum. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
24. Mitochondria antioxidant protection against cardiovascular dysfunction programmed by early-onset gestational hypoxia.
- Author
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Spiroski, Ana-Mishel, Youguo Niu, Nicholas, Lisa M., Austin-Williams, Shani, Camm, Emily J., Sutherland, Megan R., Ashmore, Thomas J., Skeffington, Katie. L., Logan, Angela, Ozanne, Susan E., Murphy, Michael P., and Giussani, Dino A.
- Published
- 2021
- Full Text
- View/download PDF
25. Agile Expertise.
- Author
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Nicholas, Lisa
- Subjects
MARKETING strategy ,MORTGAGES ,MORTGAGE loans - Abstract
An interview with producing branch manager Lisa Nicholas of mortgage lender PrimeLending in Shelton, Connecticut is presented. Topics covered include Nicholas' most creative or successful marketing strategy, her views with regards to the diversity of the local mortgage market in Shelton, Connecticut, and the unusual or difficult loan scenario she has encountered. Nicolas also talks about her views with regards to the mortgage business, and the people who have helped her succeed.
- Published
- 2016
26. Differential Effects of Exposure to Maternal Obesity or Maternal Weight Loss during the Periconceptional Period in the Sheep on Insulin Signalling Molecules in Skeletal Muscle of the Offspring at 4 Months of Age.
- Author
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Nicholas, Lisa M., Morrison, Janna L., Rattanatray, Leewen, Ozanne, Susan E., Kleemann, Dave O., Walker, Simon K., MacLaughlin, Severence M., Zhang, Song, Martin-Gronert, Malgorzata S., and McMillen, Isabella C.
- Subjects
- *
OBESITY in women , *WEIGHT loss , *PREGNANCY complications , *SHEEP as laboratory animals , *CELLULAR signal transduction , *SKELETAL muscle , *INSULIN resistance , *OBESITY risk factors - Abstract
Exposure to maternal obesity before and/or throughout pregnancy may increase the risk of obesity and insulin resistance in the offspring in childhood and adult life, therefore, resulting in its transmission into subsequent generations. We have previously shown that exposure to maternal obesity around the time of conception alone resulted in increased adiposity in female lambs. Changes in the abundance of insulin signalling molecules in skeletal muscle and adipose tissue precede the development of insulin resistance and type 2 diabetes. It is not clear, however, whether exposure to maternal obesity results in insulin resistance in her offspring as a consequence of the impact of increased adiposity on skeletal muscle or as a consequence of the programming of specific changes in the abundance of insulin signalling molecules in this tissue. We have used an embryo transfer model in the sheep to investigate the effects of exposure to either maternal obesity or to weight loss in normal and obese mothers preceding and for one week after conception on the expression and abundance of insulin signalling molecules in muscle in the offspring. We found that exposure to maternal obesity resulted in lower muscle GLUT-4 and Ser 9 phospho-GSK3α and higher muscle GSK3α abundance in lambs when compared to lambs conceived in normally nourished ewes. Exposure to maternal weight loss in normal or obese mothers, however, resulted in lower muscle IRS1, PI3K, p110β, aPKCζ, Thr 642 phospho-AS160 and GLUT-4 abundance in the offspring. In conclusion, maternal obesity or weight loss around conception have each programmed specific changes on subsets of molecules in the insulin signalling, glucose transport and glycogen synthesis pathways in offspring. There is a need for a stronger evidence base to ensure that weight loss regimes in obese women seeking to become pregnant minimize the metabolic costs for the next generation. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
27. Differential Effects of Exposure to Maternal Obesity or Maternal Weight Loss during the Periconceptional Period in the Sheep on Insulin Signalling Molecules in Skeletal Muscle of the Offspring at 4 Months of Age
- Author
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Dave Kleemann, Isabella Caroline McMillen, Song Zhang, Simon K. Walker, Malgorzata S. Martin-Gronert, Lisa M. Nicholas, Janna L. Morrison, Severence M. MacLaughlin, Leewen Rattanatray, Susan E. Ozanne, Nicholas, Lisa [0000-0003-1976-1953], Ozanne, Susan [0000-0001-8753-5144], Apollo - University of Cambridge Repository, Nicholas, Lisa M, Morrison, Janna L, Rattanatray, Leewen, Ozanne, Susan, Kleemann, Dave O, Walker, Simon K, MacLaughlin, Severence M, Zhang, Song, Martin-Gronert, Malgorzata S, and McMillen, Isabella C
- Subjects
obesity ,medicine.medical_treatment ,lcsh:Medicine ,Adipose tissue ,Muscle Proteins ,Type 2 diabetes ,0302 clinical medicine ,glycogens ,Weight loss ,Pregnancy ,insulin resistance ,Insulin ,lcsh:Science ,2. Zero hunger ,0303 health sciences ,Multidisciplinary ,biology ,Prenatal Exposure Delayed Effects ,Female ,medicine.symptom ,Research Article ,Signal Transduction ,medicine.medical_specialty ,insulin ,Offspring ,030209 endocrinology & metabolism ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,Weight Loss ,medicine ,Animals ,Obesity ,Muscle, Skeletal ,insulin signaling ,030304 developmental biology ,Sheep ,protein abundance ,lcsh:R ,medicine.disease ,Insulin receptor ,Endocrinology ,Fertilization ,biology.protein ,lcsh:Q ,Insulin Resistance ,skeletal muscles ,embryos - Abstract
Exposure to maternal obesity before and/or throughout pregnancy may increase the risk of obesity and insulin resistance in the offspring in childhood and adult life, therefore, resulting in its transmission into subsequent generations. We have previously shown that exposure to maternal obesity around the time of conception alone resulted in increased adiposity in female lambs. Changes in the abundance of insulin signalling molecules in skeletal muscle and adipose tissue precede the development of insulin resistance and type 2 diabetes. It is not clear, however, whether exposure to maternal obesity results in insulin resistance in her offspring as a consequence of the impact of increased adiposity on skeletal muscle or as a consequence of the programming of specific changes in the abundance of insulin signalling molecules in this tissue. We have used an embryo transfer model in the sheep to investigate the effects of exposure to either maternal obesity or to weight loss in normal and obese mothers preceding and for one week after conception on the expression and abundance of insulin signalling molecules in muscle in the offspring. We found that exposure to maternal obesity resulted in lower muscle GLUT-4 and Ser 9 phospho-GSK3α and higher muscle GSK3α abundance in lambs when compared to lambs conceived in normally nourished ewes. Exposure to maternal weight loss in normal or obese mothers, however, resulted in lower muscle IRS1, PI3K, p110β, aPKCζ, Thr 642 phospho-AS160 and GLUT-4 abundance in the offspring. In conclusion, maternal obesity or weight loss around conception have each programmed specific changes on subsets of molecules in the insulin signalling, glucose transport and glycogen synthesis pathways in offspring. There is a need for a stronger evidence base to ensure that weight loss regimes in obese women seeking to become pregnant minimize the metabolic costs for the next generation.
- Published
- 2013
28. Gene expression allelic imbalance in ovine brown adipose tissue impacts energy homeostasis
- Author
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Ross L. Tellam, Michael Buckley, Lisa M. Nicholas, Janna L. Morrison, Shila Ghazanfar, Tony Vuocolo, Jean Yee Hwa Yang, Isabella Caroline McMillen, Ghazanfar, Shila, Vuocolo, Tony, Morrison, Janna L, Nicholas, Lisa M, McMillen, Isabella C, Yang, Jean YH, Buckley, Michael J, and Tellam, Ross L
- Subjects
0301 basic medicine ,lcsh:Medicine ,Gene Expression ,Allelic Imbalance ,0302 clinical medicine ,Adipose Tissue, Brown ,Pregnancy ,Medicine and Health Sciences ,Homeostasis ,lcsh:Science ,genes ,2. Zero hunger ,Genetics ,education.field_of_study ,Multidisciplinary ,Gene Ontologies ,heritable trait variation ,Genomics ,Adipose Tissue ,Brown Adipose Tissue ,Epigenetics ,Female ,Anatomy ,DNA variations ,Research Article ,medicine.medical_specialty ,Population ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Genomic Imprinting ,Molecular genetics ,Genetic variation ,medicine ,Animals ,Humans ,Allele ,education ,Gene ,Evolutionary Biology ,Sheep ,Population Biology ,lcsh:R ,Biology and Life Sciences ,Computational Biology ,human disease ,Genome Analysis ,Genomic Libraries ,030104 developmental biology ,Biological Tissue ,Genetic Loci ,Expression quantitative trait loci ,Genetic Polymorphism ,lcsh:Q ,030217 neurology & neurosurgery ,Population Genetics ,Developmental Biology - Abstract
Heritable trait variation within a population of organisms is largely governed by DNA variations that impact gene transcription and protein function. Identifying genetic variants that affect complex functional traits is a primary aim of population genetics studies, especially in the context of human disease and agricultural production traits. The identification of alleles directly altering mRNA expression and thereby biological function is challenging due to difficulty in isolating direct effects of cis-acting genetic variations from indirect trans-acting genetic effects. Allele specific gene expression or allelic imbalance in gene expression (AI) occurring at heterozygous loci provides an opportunity to identify genes directly impacted by cis-acting genetic variants as indirect trans-acting effects equally impact the expression of both alleles. However, the identification of genes showing AI in the context of the expression of all genes remains a challenge due to a variety of technical and statistical issues. The current study focuses on the discovery of genes showing AI using single nucleotide polymorphisms as allelic reporters. By developing a computational and statistical process that addressed multiple analytical challenges, we ranked 5,809 genes for evidence of AI using RNA-Seq data derived from brown adipose tissue samples from a cohort of late gestation fetal lambs and then identified a conservative subgroup of 1,293 genes. Thus, AI was extensive, representing approximately 25% of the tested genes. Genes associated with AI were enriched for multiple Gene Ontology (GO) terms relating to lipid metabolism, mitochondrial function and the extracellular matrix. These functions suggest that cis-acting genetic variations causing AI in the population are preferentially impacting genes involved in energy homeostasis and tissue remodelling. These functions may contribute to production traits likely to be under genetic selection in the population. Refereed/Peer-reviewed
- Published
- 2017
29. Maternal obesity or weight loss around conception impacts hepatic fatty acid metabolism in the offspring
- Author
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Nicholas, Lisa M, Rattanatray, Leewen, Morrison, Janna L, Kleemann, David O, Walker, Simon K, Zhang, Song, MacLaughlin, Severence, and McMillen, I Caroline
- Subjects
Pregnancy Complications ,Sheep ,Liver ,Pregnancy ,Fertilization ,Fatty Acids ,Weight Loss ,Animals ,Female ,Obesity ,Newborn ,Embryo Transfer - Abstract
Refereed/Peer-reviewed
- Published
- 2014
30. The impact of maternal obesity and dietary restriction and weight loss during the periconceptional period in the sheep on insulin and insulin-like growth factor signalling in liver and skeletal muscle of the offspring
- Author
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Nicholas, Lisa Marie
- Subjects
Fetus ,Sheep ,developmental programming ,health aspects ,Insulin ,Obesity ,Prenatal influences - Abstract
Thesis (PhD)--University of South Australia, 2013. Includes bibliographical references (pages 150-175) The current global obesity epidemic has resulted in more women entering pregnancy with a body mass index in the overweight and obese range. It has been shown that the offspring of obese women are at increased risk of obesity and impaired glucose tolerance in childhood and in adult life and it has therefore been proposed that there is an ‘intergenerational cycle’ of obesity and insulin resistance. It has previously been shown in sheep that exposure to maternal obesity around the time of conception alone leads to increased adiposity in female lambs at four months of age and that dietary restriction in the obese ewe during the periconceptional period abolishes this effect. While dieting before pregnancy may have metabolic benefits for the offspring, there are also potential metabolic and endocrine costs for the offspring. The pathways and critical periods during which the metabolic consequences of maternal obesity or dietary restriction are transduced from mother to the offspring are, however, not known. We have used an embryo transfer model in the sheep to investigate the effects of exposure to either maternal obesity or to dietary restriction and weight loss in normal and obese ewes preceding and for one week after conception on the expression and abundance of insulin signalling molecules in the liver and skeletal muscle of the offspring at four months of age. We have also investigated the impact of maternal periconceptional nutrition on molecules involved in maintaining hepatic lipid oxidation and lipogenesis in the offspring. Finally, we examined the impact of either maternal obesity or dietary restriction and weight loss in normal and obese ewes on components of the insulin-like growth factor system, which along with insulin play a key role in normal mammalian fetal and postnatal growth, development and metabolism. We found that exposure of the oocyte/early embryo to maternal obesity and/or dietary restriction and weight loss resulted in differential effects on gene expression and protein abundance of molecules involved in these metabolic networks in two insulin sensitive tissues; liver and skeletal muscle. Importantly, we observed that maternal dietary restriction in obese ewes was mostly unable to abolish the effects of maternal obesity. Moreover, dietary restriction itself resulted in a suite of changes, which could negatively impact metabolism in the offspring. We also found that some of these changes were potentially the result of underlying epigenetic modifications, which occurred in the oocyte/developing embryo and persisted into postnatal life. Specifically, we observed that the expression of specific miRNAs regulating insulin signalling were more sensitive to the effects of maternal obesity whereas maternal dietary restriction and weight loss had a greater impact on DNA methylation of the IGF2 gene. In conclusion, we have shown that the periconceptional period is a developmental window that is sensitive to programming by the maternal metabolic milieu. Both a high and low maternal pre-pregnancy weight as well as the maternal metabolic response to dietary restriction each appears to increase the risk for development of insulin resistance and potentially Type 2 Diabetes Mellitus in the offspring. Importantly, this data suggests that the current clinical practice whereby dietary restriction is recommended to overweight/obese women prior to becoming pregnant is not a straightforward solution to stopping the ‘intergenerational cycle’ of obesity and insulin resistance.
- Published
- 2013
31. Effects of a bitter substance, denatonium benzoate, on pancreatic hormone secretion.
- Author
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Huang W, O'Hara SE, Xie C, Liu N, Rayner CK, Nicholas LM, and Wu T
- Subjects
- Mice, Animals, Glucagon pharmacology, Insulin pharmacology, Glucose pharmacology, Glucagon-Like Peptide 1 pharmacology, Somatostatin pharmacology, Adenosine Triphosphate pharmacology, Taste, Islets of Langerhans, Quaternary Ammonium Compounds
- Abstract
There is increasing evidence linking bitter taste receptor (BTR) signaling to gut hormone secretion and glucose homeostasis. However, its effect on islet hormone secretion has been poorly characterized. This study investigated the effect of the bitter substance, denatonium benzoate (DB), on hormone secretion from mouse pancreatic islets and INS-1 832/13 cells. DB (0.5-1 mM) augmented insulin secretion at both 2.8 mM and 16.7 mM glucose. This effect was no longer present at 5 mM DB likely due to the greater levels of cellular apoptosis. DB-stimulated insulin secretion involved closure of the K
ATP channel, activation of T2R signaling in beta-cells, and intraislet glucagon-like peptide-1 (GLP-1) release. DB also enhanced glucagon and somatostatin secretion, but the underlying mechanism was less clear. Together, this study demonstrates that the bitter substance, DB, is a strong potentiator of islet hormone secretion independent of glucose. This observation highlights the potential for widespread off-target effects associated with the clinical use of bitter-tasting substances. NEW & NOTEWORTHY We show that the bitter substance, denatonium benzoate (DB), stimulates insulin, glucagon, somatostatin, and GLP-1 secretion from pancreatic islets, independent of glucose, and that DB augments insulin release via the KATP channel, bitter taste receptor signaling, and intraislet GLP-1 secretion. Exposure to a high dose of DB (5 mM) induces cellular apoptosis in pancreatic islets. Therefore, clinical use of bitter substances to improve glucose homeostasis may have unintended negative impacts beyond the gut.- Published
- 2024
- Full Text
- View/download PDF
32. Using Point-in-Time Homeless Counts to Monitor Mortality Trends Among People Experiencing Homelessness in Los Angeles County, California, 2015‒2019.
- Author
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Nicholas W, Greenwell L, Henwood BF, and Simon P
- Subjects
- Drug Overdose mortality, Female, Humans, Los Angeles epidemiology, Male, Population Groups statistics & numerical data, Cause of Death, Ill-Housed Persons statistics & numerical data, Mortality
- Abstract
Objectives. To report trends in mortality rates, mortality rate ratios (MRRs), and causes of death among people experiencing homelessness (PEH) in Los Angeles County, California, by using annual point-in-time homeless counts and to compare findings to published longitudinal cohort studies of homeless mortality. Methods. We enumerated homeless deaths and determined causes by using 2015-2019 medical examiner‒coroner data matched to death certificate data. We estimated midyear homeless population denominators by averaging consecutive January point-in-time homeless counts. We used annual demographic surveys of PEH to estimate age- and gender-adjusted MRRs. We identified comparison studies through a literature review. Results. Mortality rates increased from 2015 to 2019. Drug overdose was the leading cause of death. Mortality was higher among White than among Black and Latino PEH. Compared with the general population, MRRs ranged from 2.8 (95% confidence interval [CI] = 2.7, 3.0) for all causes to 35.1 (95% CI = 31.9, 38.4) for drug overdose. Crude mortality rates and all-cause MRRs from comparison cohort studies were similar to those in the current study. Conclusions. These methods can be adapted by other urban jurisdictions seeking to better understand and reduce mortality in their homeless populations. ( Am J Public Health . 2021;111(12):2212-2222. https://doi.org/10.2105/AJPH.2021.306502).
- Published
- 2021
- Full Text
- View/download PDF
33. Analysis of Histone Modifications in Rodent Pancreatic Islets by Native Chromatin Immunoprecipitation.
- Author
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Sandovici I, Nicholas LM, and O'Neill LP
- Subjects
- Animals, Cell Separation, Chromatin, Gene Expression Regulation, Islets of Langerhans cytology, Mice, Nucleosomes, Rats, Real-Time Polymerase Chain Reaction, Chromatin Immunoprecipitation, Histones metabolism, Islets of Langerhans metabolism, Protein Processing, Post-Translational
- Abstract
The islets of Langerhans are clusters of cells dispersed throughout the pancreas that produce several hormones essential for controlling a variety of metabolic processes, including glucose homeostasis and lipid metabolism. Studying the transcriptional control of pancreatic islet cells has important implications for understanding the mechanisms that control their normal development, as well as the pathogenesis of metabolic diseases such as diabetes. Histones represent the main protein components of the chromatin and undergo diverse covalent modifications that are very important for gene regulation. Here we describe the isolation of pancreatic islets from rodents and subsequently outline the methods used to immunoprecipitate and analyze the native chromatin obtained from these cells.
- Published
- 2020
- Full Text
- View/download PDF
34. Early life programming in mice by maternal overnutrition: mechanistic insights and interventional approaches.
- Author
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Nicholas LM and Ozanne SE
- Subjects
- Animals, Female, Lactation, Mice embryology, Mice growth & development, Pregnancy, Maternal Inheritance physiology, Mice physiology, Nutritional Status physiology, Overnutrition physiopathology
- Abstract
Animal models have been indispensable in elucidating the potential causative mechanisms underlying the effects of maternal diet on offspring health. Of these, the mouse has been widely used to model maternal overnutrition and/or maternal obesity and to study its effects across one or more generations. This review discusses recent findings from mouse models, which resemble the human situation, i.e. overnutrition/obesity across pregnancy and lactation. It also highlights the importance of embryo transfer models in identifying critical developmental period(s) during which specific metabolic changes are programmed in the offspring. The mouse is also an excellent tool for maternal intervention studies aimed at elucidating the longer-term effects on the offspring and for defining possible maternal factors underling the programming of metabolic adversity in offspring. While knowledge of the mouse genome and the molecular tools available have allowed great progress to be made in the field, it is clear that we need to define if the effects on the offspring are mediated by maternal obesity per se or if specific components of the maternal metabolic environment are more important. We can then begin to identify at-risk offspring and to design more effective interventions for the mother and/or her child. This article is part of the theme issue 'Developing differences: early-life effects and evolutionary medicine'.
- Published
- 2019
- Full Text
- View/download PDF
35. The pathogenetic role of β-cell mitochondria in type 2 diabetes.
- Author
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Fex M, Nicholas LM, Vishnu N, Medina A, Sharoyko VV, Nicholls DG, Spégel P, and Mulder H
- Subjects
- Animals, Calcium metabolism, Energy Metabolism, Glucose metabolism, Glycolysis, Humans, Insulin Secretion physiology, Mice, Mice, Inbred C57BL, Protein Biosynthesis physiology, Transcription, Genetic physiology, Diabetes Mellitus, Type 2 physiopathology, Insulin-Secreting Cells ultrastructure, Mitochondria physiology
- Abstract
Mitochondrial metabolism is a major determinant of insulin secretion from pancreatic β-cells. Type 2 diabetes evolves when β-cells fail to release appropriate amounts of insulin in response to glucose. This results in hyperglycemia and metabolic dysregulation. Evidence has recently been mounting that mitochondrial dysfunction plays an important role in these processes. Monogenic dysfunction of mitochondria is a rare condition but causes a type 2 diabetes-like syndrome owing to β-cell failure. Here, we describe novel advances in research on mitochondrial dysfunction in the β-cell in type 2 diabetes, with a focus on human studies. Relevant studies in animal and cell models of the disease are described. Transcriptional and translational regulation in mitochondria are particularly emphasized. The role of metabolic enzymes and pathways and their impact on β-cell function in type 2 diabetes pathophysiology are discussed. The role of genetic variation in mitochondrial function leading to type 2 diabetes is highlighted. We argue that alterations in mitochondria may be a culprit in the pathogenetic processes culminating in type 2 diabetes., (© 2018 Society for Endocrinology.)
- Published
- 2018
- Full Text
- View/download PDF
36. Impact of maternal overnutrition on gluconeogenic factors and methylation of the phosphoenolpyruvate carboxykinase promoter in the fetal and postnatal liver.
- Author
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Rattanatray L, Muhlhausler BS, Nicholas LM, Morrison JL, and McMillen IC
- Subjects
- Animals, Female, Gene Expression Regulation, Developmental, Liver embryology, Liver enzymology, Pregnancy, Sheep embryology, Sheep growth & development, DNA Methylation, Gluconeogenesis genetics, Liver metabolism, Overnutrition, Phosphoenolpyruvate Carboxykinase (ATP) genetics, Promoter Regions, Genetic
- Abstract
Background: Exposure to maternal obesity or hyperglycemia increases the risk of obesity and poor glucose tolerance in the offspring. We hypothesized that maternal overnutrition in late pregnancy would result in (i) lower methylation in the promoter region of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C; PCK1) and (ii) higher expression of hepatic gluconeogenic factors in the fetal and postnatal lamb., Methods: Ewes were fed 100% (n = 18) or ~155% (n = 17) of energy requirements from 115 d gestation, and livers were collected at ~140 d gestation or 30 d postnatal age., Results: Maternal overnutrition resulted in a decrease in hepatic expression of the mitochondrial form of PEPCK (PEPCK-M; PCK2) but not of PEPCK-C or glucose-6-phosphatase (G6PHOS) before and after birth. Hepatic expression of peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1), peroxisome proliferator-activated receptor α (PPARα), PEPCK-C, G6PHOS, and 11β hydroxysteroid dehydrogenase type 1 (11βHSD1), but not PEPCK-M, was higher in the postnatal lamb compared with that in the fetal lamb. The level of PCK1 methylation was paradoxically approximately twofold higher in the postnatal liver compared with that in the fetal liver., Conclusion: Maternal overnutrition programs a decrease in hepatic PEPCK-M in the offspring and as ~50% of total hepatic PEPCK is PEPCK-M, the longer-term consequences of this decrease may be significant.
- Published
- 2014
- Full Text
- View/download PDF
37. GPs' views on active nutrition management for their patients.
- Author
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Nicholas L, Pond D, and Roberts DC
- Subjects
- Adult, Aged, Clinical Competence, Family Practice statistics & numerical data, Female, Health Care Surveys, Humans, Male, Middle Aged, New South Wales, Patient Education as Topic statistics & numerical data, Referral and Consultation statistics & numerical data, Attitude of Health Personnel, Nutrition Therapy statistics & numerical data, Physicians, Family statistics & numerical data
- Published
- 2004
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