Jacqueline M Stephens
Lsu Pennington Biomedical Research Ctr
Project start date: 1999-09-01
Project end date: 2014-01-31
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Jacqueline M Stephens
REGULATION AND ACTIVATION OF STATS IN ADIPOCYTES
Jacqueline M Stephens, Associate Professor
Louisiana State Univ A&m Col Baton Rouge 330 Thomas Boyd Hall Baton Rouge, La 70803
Grant 5R01DK052968-04 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: NTN
Abstract: Adipocytes are highly specialized cells which play a central role in lipid homeostasis and the maintenance of energy balance in vertebrate organisms. These cells store energy in the form of triglycerides during periods of nutritional abundance and release it in the form of free fatty acids at times of nutritional deprivation. Pathological conditions associated with altered adipocyte cell number or function include obesity and several lipodystrophy syndromes. Obesity, an excessive accumulation of adipose tissue, is a common disorder which affects over 30 percent of Americans. In humans, obesity is an independent risk factor for non-insulin dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease and is a major contributor to morbidity and mortality. Recent studies suggest that obesity and its related disorders may be linked to a breakdown in the regulatory mechanisms which control the expression of metabolic genes in adipocytes. Significant advances toward an understanding of these regulatory processes have been made by the identification of transcription factors which regulate adipocyte differentiation and gene expression. To date, members of two transcription factor families, C/EBP (C/AAAT Enhancer Binding Proteins) and PPAR (Peroxisome Proliferator Activated Receptors) have been shown to be induced during adipocyte differentiation and play a critical role in the regulation of fat-specific genes. Our recent investigations have demonstrated that an additional family of transcription factors are induced during adipocyte differentiation. The STATs (Signal Transducers and Activators of Transcription) comprise a family of transcription factors which reside in the cytoplasm of resting cells. Unlike either C/EBPs or PPARs, STATs can be rapidly activated to control gene expression. In a manner equivalent to both C/EBPalpha and PPARgamma, expression of three STAT family members correlates with lipid accumulation. Since STAT family members have unique tissue distributions and are highly expressed in adipocytes, we hypothesize that STATs play a key role in the regulation of adipocyte gene expression. To test this hypothesis, we will examine the regulation and activation of STATs in adipocytes. We have also designed a set of experiments to elucidate the function of these proteins in adipocytes. These studies may lead to insights into the molecular mechanisms regulating energy homeostasis and may have a profound impact on the defects underlying obesity and NIDDM.
Keywords: adipocyte, gene expression, genetic regulation, genetic transcription, lipid metabolism, transcription factor, cell differentiation, diet, dietary lipid, fasting, gene induction /repression, genetic promoter element, growth factor, insulin sensitivity /resistance, interferon gamma, leukemia inhibitory factor, obesity, phosphorylation, protein structure function, somatotropin, DNA footprinting, gel mobility shift assay, laboratory rat, nutrition related tag
Project start date: 1999-09-01
Project end date: 2003-12-19
5R01DK052968-04 (2002): $189070
5R01DK052968-03 (2001): $185448
5R01DK052968-02 (2000): $176467
1R01DK052968-01A1 (1999): $177374
THE REGULATION AND ACTIVATION OF STATS IN ADIPOCYTES
Jacqueline M Stephens, George C. Kent Professor
Louisiana State Univ A&m Col Baton Rouge, 202 Himes Hall, Baton Rouge, La 70803
Grant 5R01DK052968-11 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Adipocytes are highly specialized cells that play a major role in energy homeostasis in vertebrates. Obesity is the primary disease of fat cells and the most common metabolic disorder in the industrial world. Obesity affects >30% of the adult population in the United States and is a major risk factor for the development of non-insulin dependent diabetes mellitus (NIDDM), cardiovascular disease, and hypertension. Recent studies suggest that obesity and its related disorders may be linked to a breakdown in the regulatory mechanisms which control the expression of a variety of genes in adipocytes. Significant advances towards an understanding of these regulatory processes have been made by studying the function of transcription factors which regulate the differentiation of fat cells and are involved in the modulation of adipocyte gene expression. It is well recognized that several transcription factors are induced during adipocyte differentiation, play a critical role in the regulation of adipocyte gene expression, and are altered in conditions of obesity and/or insulin resistance. We have focused on STATs (Signal Transducers and Activators of Transcription), a family of transcription factors whose activity is largely controlled by hormone induced tyrosine phosphorylation. Our efforts have focused on two STAT proteins, STAT5A and STAT 5B, whose expression is induced during adipogenesis. Studies from our laboratory and several others have demonstrated the adipogenic capabilities of STAT 5A. Although STAT5A promotes lipid deposition in preadipocytes, there is a variety of observations to indicate that STAT 5A has anti-lipogenic actions in mature adipocytes. Growth hormone, a potent inducer of STAT 5 proteins is well known to have effects that are lipolytic, anti-lipogenic and diabetogenic. It is known that STATs can have cell specific functions, and we hypothesize that STAT5 proteins play a vital role in the regulation of genes involved in lipid metabolism and insulin resistance in adipocytes. Our preliminary studies demonstrate that STAT5 tyrosine phosphorylation in white adipose tissue is altered in rodent models of obesity. In addition, we have evidence to suggest that STAT 5 proteins may affect the endocrine properties of adipocytes by regulating the expression of several adipokines. The studies outlined in the specific aims focus on understanding the function of STAT 5 proteins in mature adipocytes and how these transcription factors affect lipogenesis, insulin sensitivity, and the production of endocrine factors from fat cells. Significant advances towards understanding obesity and diabetes have been made by studying the function of transcription factors which are involved in controlling adipocyte gene expression. Our studies focus on understanding the function of STAT 5 proteins in fat cells and how these transcription factors affect lipogenesis, insulin sensitivity, and the production of endocrine factors in adipocytes
Keywords: 21+ years old; 3T3-L1 Cells; Adipocytes; Adipose Cell; Adipose tissue; Adult; Affect; Autoregulation; Blood Pressure, High; Cardiovascular Diseases; Cells; Chemotherapy-Hormones/Steroids; Circadian Rhythms; Data; Deposit; Deposition; Development; Diabetes Mellitus; Diabetes Mellitus, Adult-Onset; Diabetes Mellitus, Ketosis-Resistant; Diabetes Mellitus, Non-Insulin-Dependent; Diabetes Mellitus, Noninsulin Dependent; Diabetes Mellitus, Slow-Onset; Diabetes Mellitus, Stable; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type II; Disease; Disorder; Diurnal Rhythm; EC 2.3.1.85; Ectopic Expression; Endocrine; Endocrine Gland Secretion; Family; Fat Cells; Fats; Fatty Acid Synthetase Complex; Fatty Tissue; Fatty acid glycerol esters; Fatty-acid synthase; GHN; Gene Action Regulation; Gene Expression; Gene Expression Regulation; Gene Regulation; Gene Regulation Process; Gene Targeting; Gene Transcription; Genes; Genetic Transcription; Growth Hormone; Growth Hormone 1; Homeostasis; Hormones; Human, Adult; Hypertension; Insulin Resistance; LTH; Laboratories; Lactogenic Hormone, Pituitary; Link; Lipids; Lipocytes; MODY; Mammals, Rodents; Mammotropic Hormone, Pituitary; Mammotropin; Mature Lipocyte; Mature fat cell; Maturity-Onset Diabetes Mellitus; Mediator; Mediator of Activation; Mediator of activation protein; Metabolic Diseases; Metabolic Disorder; Metabolism, Lipids/Lipoproteins/Membrane Constituents; NIDDM; Non-Insulin Dependent Diabetes; Non-Insulin-Dependent Diabetes Mellitus; Nutritional status; Nyctohemeral Rhythm; Obesity; PRL; PRL (Prolactin); Physiological Homeostasis; Pituitary Growth Hormone; Play; Population; Process; Production; Prolactin; Property; Property, LOINC Axis 2; Proteins; Publishing; RNA Expression; Regulation; Risk Factors; Rodent; Rodent Model; Rodentia; Rodentias; Role; STAT protein; STAT5; STAT5A; STAT5A gene; STAT5B; STAT5B gene; STH; Signal Transducer and Activator of Transcription; Somatotropin; T2D; T2DM; Targetings, Gene; Testing; Therapeutic Hormone; Thesaurismosis; Transcription; Transcription, Genetic; Twenty-Four Hour Rhythm; Type 2 diabetes; Type II diabetes; Tyrosine Phosphorylation; United States; Vascular Hypertensive Disease; Vascular Hypertensive Disorder; Vertebrate Animals; Vertebrates; adipocyte development; adipocyte differentiation; adipogenesis; adipokines; adipose; adiposity; adult human (21+); adult onset diabetes; base; cardiovascular disorder; circadian; circadian process; corpulence; corpulency; corpulentia; daily biorhythm; diabetes; diabetic; disease/disorder; diurnal variation; experiment; experimental research; experimental study; fat metabolism; gene product; hGHN; hormone resistance; hyperpiesia; hyperpiesis; hypertensive disease; in vivo; insulin resistant; insulin sensitivity; ketosis resistant diabetes; knock-down; lipid biosynthesis; lipid metabolism; lipogenesis; luteotropic hormone; luteotropin; maturity onset diabetes; metabolism disorder; obese; obese people; obese person; obese population; public health relevance; research study; social role; somatotropic hormone; transcription factor; vertebrata; white adipose tissue; yellow adipose tissue
Project start date: 1999-09-01
Project end date: 2014-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2011
PFA/PA: PA-07-070
5R01DK052968-11 (2010): $349272
5R01DK052968-08 (2007): $313610
5R01DK052968-07 (2006): $322977
5R01DK052968-06 (2005): $330750
2R01DK052968-05A1 (2004): $328001
Sponsored Links Excellgen http://Excellgen.com
REGULATION AND ACTIVATION OF STATS IN ADIPOCYTES
Jacqueline M Stephens, Associate Professor
Zoology And Physiologylouisiana State Univ A&m Col Baton Rouge
202 Himes Hall
baton Rouge, La 70803
Grant 1R55DK052968-01 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: NTN
Abstract: Adipocytes are highly specialized cells that play a central role in lipid homeostasis and the maintenance of energy balance in vertebrate organisms. These cells store energy in the form of triglycerides during periods of nutritional abundance and release it in the form of free fatty acids at times of nutrional deprivation. Pathological conditions associated with altered adipocytes cell number or function include obesity and several lipodystrophy syndromes. Obesity, an excessive accumulation of adipose tissue, is a common disorder that affects over 30% of americans. In humans, obesity is an independent risk factor for non-insulin dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease and therefore is a major contributor to morbidity and mortality. Recent studies suggest that obesity and its related disorders may be linked to a breakdown in the regulatory mechanisms which control the expression of metabolic genes in adipocytes. Significant advances toward an understanding of these regulatory processes have been made by the identification of transcription factors that regulate the differentiation of preadipocytes to adipocytes and are involved in the maintenance of fact-specific genes. To date, members of two transcription factor families, C/EBP (C/AAAT Enhancer Binding Proteins) and PPAR (Peroxisome Proliferator Activated Receptor) have been shown to be induced during adipocyte differentiation and play a critical role in the regulation of fat specific genes. Our recent investigations have demonstrated that an additional family of transcription factors are induced during adipocyte differentiation. The STATs (Signal Transducers and Activators of Transcription) comprise a family of transcription factors that reside in the cytoplasm of resting cells. Unlike either C/EBPs or PPARs, STATs can be rapidly activated to control gene expression and are likely to play a significant role in the transriptional regulation in fact cells. In a manner equivalent to both C/EBP alpha and PPARnu, expression of two STAT family members correlates with lipid accumulation. Since STAT family members have unique tissue distributions and are highly expressed in adipocytes, we hypothesize that STATs will be involved in the regulation of adiopcyte gene expression. To test this hypothesis, we will examine the regulation and activation of STATs in adipocytes. These studies may lead to insights into the molecular mechanisms regulating energy homeostasis and may have a profound impact on the defects underlaying obesity and NIDDM
Keywords: adipocyte, biological signal transduction, transcription factor cell differentiation 3T3 cell
Project start date: 1997-09-30
Project end date: 1999-08-31
1R55DK052968-01 (1997): $100000
Jacqueline M Stephens
Lsu Pennington Biomedical Research Ctr
Project start date: 1999-09-01
Project end date: 2014-01-31