, a bio/informatics shared resource is still "open for business" - Visit the CDS website


Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 81 to 90 of 90

Publication Record

Connections

Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities.
Niswender KD, Schwartz MW
(2003) Front Neuroendocrinol 24: 1-10
MeSH Terms: Animals, Diabetes Mellitus, Eating, Feeding Behavior, Hypoglycemic Agents, Hypothalamus, Insulin, Intracellular Fluid, Leptin, Mice, Mice, Knockout, Models, Biological, Neurons, Obesity, Phosphatidylinositol 3-Kinases, Receptor Cross-Talk, Signal Transduction
Show Abstract · Added February 15, 2016
The adipocyte-derived hormone leptin and the pancreatic beta cell-derived hormone insulin each function as afferent signals to the hypothalamus in an endocrine feedback loop that regulates body adiposity. Although these two hormones, and the receptors on which they act, are unrelated and structurally distinct, they exert overlapping effects in the arcuate nucleus, a key hypothalamic area involved in energy homeostasis. Defects in either insulin or leptin signaling in the brain result in hyperphagia, disordered glucose homeostasis, and reproductive dysfunction. To explain this striking physiological overlap, we hypothesize that hypothalamic insulin and leptin signaling converge upon a single intracellular signal transduction pathway, known as the insulin-receptor-substrate phosphatidylinositol 3-kinase pathway. Here we synthesize data from a variety of model systems in which such "cross-talk" between insulin and leptin signal transduction has either been observed or can be inferred, discuss our own data demonstrating that insulin and leptin both activate hypothalamic phosphatidylinositol 3-kinase signaling, and discuss the significance of such convergence with respect to neuronal function in normal individuals and in pathological states such as obesity. Identification of the key early molecular events mediating the action of both insulin and leptin in hypothalamic neurons promises new insight into the regulation of these neurons in health and disease.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Immunocytochemical detection of phosphatidylinositol 3-kinase activation by insulin and leptin.
Niswender KD, Gallis B, Blevins JE, Corson MA, Schwartz MW, Baskin DG
(2003) J Histochem Cytochem 51: 275-83
MeSH Terms: Animals, Cattle, Cells, Cultured, Endothelium, Vascular, Enzyme Activation, Hepatocytes, Immunohistochemistry, Insulin, Insulin Receptor Substrate Proteins, Intracellular Signaling Peptides and Proteins, Leptin, Male, Microscopy, Fluorescence, Phosphatidylinositol 3-Kinases, Phosphoproteins, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Rats, Rats, Wistar, Receptor, Insulin, Time Factors
Show Abstract · Added February 15, 2016
Intracellular signaling mediated by phosphatidylinositol 3-kinase (PI3K) is important for a number of cellular processes and is stimulated by a variety of hormones, including insulin and leptin. A histochemical method for assessment of PI3K signaling would be an important advance in identifying specific cells in histologically complex organs that are regulated by growth factors and peptide hormones. However, current methods for detecting PI3K activity require either homogenization of the tissue or cells or the ability to transfect probes that bind to phosphatidylinositol 3,4,5 trisphosphate (PIP3), the reaction product of PI3K catalysis. Here we report the validation of an immunocytochemical method to detect changes in PI3K activity, using a recently developed monoclonal antibody to PIP3, in paraformaldehyde-fixed bovine aortic endothelial cells (BAECs) in culture and in hepatocytes of intact rat liver. Treatment with either insulin or leptin increased BAEC PIP3 immunoreactivity, and these effects were blocked by pretreatment with PI3K inhibitors. Furthermore, infusion of insulin into the hepatic portal vein of fasted rats caused an increase of PIP3 immunostaining in hepatocytes that was associated with increased serine phosphorylation of the downstream signaling molecule protein kinase B/Akt (PKB/Akt). We conclude that immunocytochemical PIP3 staining can detect changes in PI3K activation induced by insulin and leptin in cell culture and intact liver.
0 Communities
1 Members
0 Resources
22 MeSH Terms
Leptin regulates bone formation via the sympathetic nervous system.
Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G
(2002) Cell 111: 305-17
MeSH Terms: Adrenergic beta-Antagonists, Animals, Cells, Cultured, Hypothalamus, Leptin, Mice, Mice, Inbred C57BL, Neuropeptides, Obesity, Oligopeptides, Osteoblasts, Osteogenesis, Pyrrolidonecarboxylic Acid, Receptor, Melanocortin, Type 4, Receptors, Adrenergic, beta, Receptors, Corticotropin, Receptors, Leptin, Sympathetic Nervous System
Show Abstract · Added November 14, 2013
We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice.
Yahagi N, Shimano H, Hasty AH, Matsuzaka T, Ide T, Yoshikawa T, Amemiya-Kudo M, Tomita S, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Nagai R, Ishibashi S, Yamada N
(2002) J Biol Chem 277: 19353-7
MeSH Terms: Adipose Tissue, Animals, Blotting, Northern, CCAAT-Enhancer-Binding Proteins, Crosses, Genetic, DNA-Binding Proteins, Fatty Liver, Genotype, Insulin Resistance, Leptin, Lipid Metabolism, Lipoprotein Lipase, Liver, Mice, Mice, Inbred C57BL, Mice, Transgenic, Obesity, Phenotype, RNA, Messenger, Sterol Regulatory Element Binding Protein 1, Transcription Factors, Triglycerides
Show Abstract · Added March 27, 2013
Obesity is a common nutritional problem often associated with diabetes, insulin resistance, and fatty liver (excess fat deposition in liver). Leptin-deficient Lep(ob)/Lep(ob) mice develop obesity and those obesity-related syndromes. Increased lipogenesis in both liver and adipose tissue of these mice has been suggested. We have previously shown that the transcription factor sterol regulatory element-binding protein-1 (SREBP-1) plays a crucial role in the regulation of lipogenesis in vivo. To explore the possible involvement of SREBP-1 in the pathogenesis of obesity and its related syndromes, we generated mice deficient in both leptin and SREBP-1. In doubly mutant Lep(ob/ob) x Srebp-1(-/-) mice, fatty livers were markedly attenuated, but obesity and insulin resistance remained persistent. The mRNA levels of lipogenic enzymes such as fatty acid synthase were proportional to triglyceride accumulation in liver. In contrast, the mRNA abundance of SREBP-1 and lipogenic enzymes in the adipose tissue of Lep(ob)/Lep(ob) mice was profoundly decreased despite sustained fat, which could explain why the SREBP-1 disruption had little effect on obesity. In conclusion, SREBP-1 regulation of lipogenesis is highly involved in the development of fatty livers but does not seem to be a determinant of obesity in Lep(ob)/Lep(ob) mice.
0 Communities
1 Members
0 Resources
22 MeSH Terms
PRL-releasing peptide interacts with leptin to reduce food intake and body weight.
Ellacott KL, Lawrence CB, Rothwell NJ, Luckman SM
(2002) Endocrinology 143: 368-74
MeSH Terms: Animals, Body Temperature, Body Weight, Depression, Chemical, Dorsomedial Hypothalamic Nucleus, Drug Interactions, Eating, Energy Metabolism, Fluorescent Antibody Technique, Indirect, Hypothalamic Hormones, Immunohistochemistry, In Situ Hybridization, Injections, Intraventricular, Leptin, Male, Neuropeptides, Obesity, Prolactin, Prolactin-Releasing Hormone, Rats, Rats, Sprague-Dawley, Rats, Zucker, Solitary Nucleus, Tyrosine 3-Monooxygenase, Ventromedial Hypothalamic Nucleus
Show Abstract · Added December 10, 2013
PRL-releasing peptide (PrRP) is a novel anorexigen that reduces food intake and body weight gain in rats. In common with other anorexigens, PrRP mRNA expression is reduced during states of negative energy balance, i.e. lactation and fasting in female rats. In this study, we examined the interaction between PrRP and the adiposity signal, leptin, which interacts with a number of peptidergic systems in the brain to regulate energy homeostasis. Intracerebroventricular coadministration of 4 nmol PrRP and 1 microg leptin in rats resulted in additive reductions in nocturnal food intake and body weight gain and an increase in core body temperature compared with each peptide alone. We show also, by quantitative in situ hybridization, that PrRP mRNA is reduced in fasted male rats and obese Zucker rats, indicating that PrRP mRNA expression, like that of other anorexigens, may be regulated by leptin. Finally we show, using immunohistochemistry, that greater than 90% of PrRP neurons in all regions where PrRP is expressed contain leptin receptors. Thus, we provide evidence for PrRP neurons forming part of the leptin-sensitive brain circuitry involved in the regulation of food intake and energy homeostasis.
0 Communities
1 Members
0 Resources
25 MeSH Terms
Intracellular signalling. Key enzyme in leptin-induced anorexia.
Niswender KD, Morton GJ, Stearns WH, Rhodes CJ, Myers MG, Schwartz MW
(2001) Nature 413: 794-5
MeSH Terms: Animals, Anorexia, Chromones, DNA-Binding Proteins, Eating, Enzyme Activation, Enzyme Inhibitors, Hypothalamus, Insulin, Leptin, Morpholines, Obesity, Phosphatidylinositol 3-Kinases, Phosphoinositide-3 Kinase Inhibitors, Rats, STAT3 Transcription Factor, Signal Transduction, Trans-Activators, alpha-MSH
Added February 15, 2016
0 Communities
1 Members
0 Resources
19 MeSH Terms
Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor.
Hasty AH, Shimano H, Osuga J, Namatame I, Takahashi A, Yahagi N, Perrey S, Iizuka Y, Tamura Y, Amemiya-Kudo M, Yoshikawa T, Okazaki H, Ohashi K, Harada K, Matsuzaka T, Sone H, Gotoda T, Nagai R, Ishibashi S, Yamada N
(2001) J Biol Chem 276: 37402-8
MeSH Terms: Animals, Arteriosclerosis, Diet, Disease Models, Animal, Hypercholesterolemia, Hypertriglyceridemia, Leptin, Lipoproteins, Mice, Mice, Inbred C57BL, Receptors, LDL, Receptors, Leptin
Show Abstract · Added March 27, 2013
Leptin-deficient mice (ob/ob) are an excellent murine model for obesity, insulin resistance, and diabetes, all of which are components of a multiple risk factor syndrome that, along with hypercholesterolemia, precipitates a potential high risk for atherosclerosis. In the current study, we show an unexpectedly severe hyperlipidemia in ob/ob mice on a background of low density lipoprotein receptor (LDLR) deficiency (-/-). Doubly mutant mice (LDLR-/-;ob/ob) exhibited striking elevations in both total plasma cholesterol (TC) and triglyceride (TG) levels (1715 +/- 87 and 1016 +/- 172 mg/dl, respectively), at age 3-4 months, resulting in extensive atherosclerotic lesions throughout the aorta by 6 months. Lipoprotein analyses revealed the elevated TC and TG levels to be due to a large increase in an apoB-containing broad-beta remnant lipoprotein fraction. While fasting, diet restriction, and low level leptin treatment significantly lowered TG levels, they caused only slight changes in TC levels. Hepatic cholesterol and triglyceride contents as well as mRNA levels of cholesterologenic and lipogenic enzymes suggest that leptin deficiency increased hepatic triglyceride production but did not change cholesterol production in ob/ob mice regardless of their LDLR genotype. These data provide evidence that the hypertriglyceridemia and hypercholesterolemia in the doubly mutant mice are caused by distinct mechanisms and point to the possibility that leptin might have some impact on plasma cholesterol metabolism, possibly through an LDLR-independent pathway. This model will be an excellent tool for future studies on the relationship between impaired fuel metabolism, increased plasma remnant lipoproteins, diabetes, and atherosclerosis.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Plasma leptin association with body composition and energy expenditure in sickle cell disease.
Buchowski MS, Simmons LA, Chen KY, Flakoll PJ, Mellen BG, Turner EA
(2000) J Am Coll Nutr 19: 228-36
MeSH Terms: Adolescent, Adult, African Continental Ancestry Group, Anemia, Sickle Cell, Basal Metabolism, Body Composition, Body Mass Index, Diet, Energy Intake, Energy Metabolism, Fasting, Female, Humans, Leptin, Male, Sex Characteristics
Show Abstract · Added December 10, 2013
OBJECTIVE - To examine the association between fasting plasma leptin concentrations and the hypercatabolic state observed in sickle cell disease (SCD).
METHODS - Plasma leptin concentration and resting energy expenditure (REE) were measured in 37 SCD patients (10 men, 12 boys 14 to 18 years-old, seven women, and eight girls 14 to 18 year-old) and in 37 age, gender and fat mass (FM) matched controls. Body composition was measured hydrostatically, REE by whole room-indirect calorimeter, and plasma leptin using an RIA kit.
RESULTS - Plasma leptin concentration and leptin normalized for body fat (ng/dL*kg FM(-1)) were significantly lower in SCD patients than in non-SCD controls (4.00+/-3.23 vs. 9.94+/-14.69, p=0.021 and 0.406+/-0.260 vs. 0.643+/-0.561, p=0.024, respectively). A positive linear association between log plasma leptin and FM was observed in both males and females, adjusting for age and SCD status. The strength of this association was greater in females compared with males (slope=0.699 and 0.382 log ng/mL per 10 kg FM, respectively; p=0.013). SCD patients on average demonstrated a higher REE, adjusting for FFM (p<0.0001). Log plasma leptin and FM were not statistically significant predictors of REE after adjustment for FFM and SCD.
CONCLUSIONS - Once corrected for body composition, mean plasma leptin concentration was significantly lower among female SCD patients than among non-SCD matched controls. Although REE was higher in SCD patients, there is no simple association between leptin and REE in SCD.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Genetic markers at the leptin (OB) locus are not significantly linked to hypertension in African Americans.
Rutkowski MP, Klanke CA, Su YR, Reif M, Menon AG
(1998) Hypertension 31: 1230-4
MeSH Terms: Adipose Tissue, Adult, African Continental Ancestry Group, Body Mass Index, Data Interpretation, Statistical, Exons, Female, Genetic Linkage, Genetic Markers, Genotype, Humans, Hypertension, Leptin, Male, Middle Aged, Obesity, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Proteins, Quantitative Trait, Heritable
Show Abstract · Added December 10, 2013
Increased body mass index (BMI) has been correlated with increased blood pressure in human populations. To examine the role of the leptin gene (OB) in essential hypertension in African Americans, we performed affected sib pair analysis on a set of 103 hypertensive African American sibships using four highly polymorphic markers at the human leptin locus. No evidence of linkage was detected between these markers and the phenotype of essential hypertension either in these sibships or in a severely obese subset of 46 sibships in which each sibling had a BMI > or = 85th percentile for the US population. Using BMI rather than hypertension as a quantitative trait, we found significant linkage for the marker D7S504 (P=0.029) but not for the other markers. Significance strengthened in the overweight subset of sibships for this marker (P=0.001), and there was a trend of lower P values for the other three markers. However, multipoint analysis with the use of all four markers simultaneously to estimate linkage between BMI and the leptin locus did not demonstrate a statistically significant relationship. Analysis of the coding region of the leptin gene (exons 2 and 3) by single-strand conformational polymorphism revealed a rare Ile-Val polymorphism at amino acid 45 but revealed no other alterations. These results suggest that the OB gene is not a major contributor to the phenotype of essential hypertension in African Americans, although a minor contribution to the phenotype of extreme obesity in this group cannot be ruled out.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Hypothalamic CART is a new anorectic peptide regulated by leptin.
Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, Clausen JT, Jensen PB, Madsen OD, Vrang N, Larsen PJ, Hastrup S
(1998) Nature 393: 72-6
MeSH Terms: Animals, Anorexia, Arcuate Nucleus of Hypothalamus, Cloning, Molecular, Escherichia coli, Fasting, Feeding Behavior, Gene Expression Regulation, Hypothalamus, Immunoenzyme Techniques, Leptin, Mice, Nerve Tissue Proteins, Neuropeptide Y, Obesity, Proteins, RNA, Messenger, Rats, Rats, Wistar, Rats, Zucker, Recombinant Fusion Proteins, Signal Transduction
Show Abstract · Added August 18, 2010
The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.
0 Communities
0 Members
2 Resources
22 MeSH Terms