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Diet induced obese mice retain endogenous leptin action – Diet-induced obese mice retain endogenous leptin action.

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Sunday, June 19, 2016
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  • I agree, dismiss this banner. We hypothesized that blockade of the LEPR in mouse models of obesity would give an estimate of endogenous leptin action reflected in changes in food intake and BW.

  • ShihS.

  • Skip to search form Skip to main content You are currently offline. Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin signaling.

  • Cell Metab33 6

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BioStudies: supplemental material and supporting data. Figures and Topics from this paper. Publication types Research Support, N. Leptin resistance during aging is independent of fat mass. Explore citation contexts and check if this article has been supported or disputed.

Here there seems to be an active attempt, possibly driven by increased plasma leptin concentration, to control the rate of excess fat gain by significantly reducing food intake. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. Secondly, we examined peripheral and central exogenous leptin sensitivity in mice fed high- or low-fat diets for 1, 8 or 19 weeks. A Epididymal fat mass; B perirenal fat mass; C inguinal fat mass; D plasma leptin concentration in mice fed a high-fat or low-fat diet for 1, 8, 15 and 19 weeks; E the length of tibia in mice fed either a high-fat or low-fat diet for 1, 8, 15 and 19 weeks.

  • The antagonist increased feeding and body weight BW in lean mice, but not in obese models of leptin… Expand. These findings in a standard animal model of obesity often cited as leptin resistant indicate that the current view on the role of leptin action in obesity needs revision.

  • High-fat diet treatment for 20 wk revealed that, compared with normal mice, the LepTg mice had an increased susceptibility to diet-induced obesity, as demonstrated by their rate of weight gain, higher accumulation of sc white adipose tissue mass, hypertrophy of adipocytes, and normalization of their reduced metabolic parameters. P CFD.

  • In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese DIO mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. See other articles in PMC that cite the published article.

High-fat diet treatment for 20 wk revealed that, compared with normal mice, the LepTg mice had an increased susceptibility to diet-induced obesity, as demonstrated by their rate of weight gain, higher accumulation of sc white adipose tissue mass, hypertrophy of adipocytes, and normalization of their reduced metabolic parameters. The tissue was washed as much as possible from blood, weighed and cut into 4, 8, and 16 mg for the LepTg mice and 4, 8, 16, 32, 64,and mg for normal mice. Charles, MO. Experimentally induced hyperleptinemia in rodents via exogenous leptin treatment results in a lean phenotype caused by a decrease in food intake and an increase in energy expenditure 14 — Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. When they treated the mouse withleptin, it stopped eating so much and started losing weight.

Loss of pericyte smoothened activity in mice with genetic deficiency of leptin. The role of leptin in health and disease. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Hyperleptinemia is required for the development of leptin resistance. Although this hypothesis remains to be corroborated experimentally, it is supported by considerable evidence suggesting age-dependent changes in leptin action Gabriely et al.

References

Article Google Scholar. Leptin levels reflect lipid content in mice: evidence for diet-induced resistance to leptin action Nature Med 1 : — Close mobile search navigation Article Navigation.

  • D'Alessio DA 4 .

  • Here there seems to be an active attempt, possibly driven by increased plasma leptin concentration, to control the rate of excess fat gain by significantly reducing food intake. Issue Date : 01 May

  • Norman LA 1. Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons.

  • View 3 excerpts, references background.

  • Similarly, after an i.

Peripheral, but not central, leptin insensitivity is evident by 8 weeks of HFF. Figure 2. The findings advance knowledge about leptin and weight gain, and also suggest a The absorbance of the dye at nm was normalized to the amount of tissue used for the differentiation experiment and expressed as absorbance units per 10 mg of WAT. Lin S, Huang XF. In vitro growth and differentiation of preadipocytes from normal and LepTg mice. Totowa, NJ : Humana Press ; —

Obesity research finds leptin hormone isn't the overeating culprit. Results Experiment 1: measurements of body nice, calorie intake, fat storage and plasma leptin in mice fed a high- or low-fat diet for 1, 8, 15 or 19 weeks A significant increase in body weight gain in mice fed the high-fat diet was evident after only 2 weeks of high-fat feeding, and this trend continued throughout the dietary protocol Figure 1A. Food spillage was determined as follows: any food that spilled was collected on absorbent paper placed beneath the cages in which the mice were kept. Transgenic mice overexpressing leptin accumulate adipose mass at an older, but not younger age. Download citation.

Leptin levels reflect endogenkus lipid content in mice: evidence for diet-induced resistance to leptin action. Since leptin receptor antagonism reduced Socs3 gene expression, p-STAT3 levels, and the expression of a target gene, Pomc Munzberg et al. The cellular and molecular bases of leptin and ghrelin resistance in obesity. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication.

Materials and Methods

ShihS. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil red O. Peripheral, but not central, leptin insensitivity is evident by 8 weeks of HFF. However, LFF mice, after i. Several theories have been proposed to account for the apparent leptin insensitivity.

Norma O Rizzo Dist Kim. Cited by: 3 articles PMID: Leptin revisited: its mechanism of action and potential for treating diabetes. Effects of gut microbiota on leptin expression and body weight are lessened by high-fat diet in mice. Galbraith Road. Physiol Behav, 17 Oct Author information Copyright and License information Disclaimer.

Nihon Rinsho71 inudced01 Feb Hyperleptinemia is required for the development of leptin resistance. Daily injection of PLA increases energy intake aBW b and BW change c in lean chow-fed control mice but not in mice voided of endogenous leptin signaling. We hypothesized that blockade of the LEPR in mouse models of obesity would give an estimate of endogenous leptin action reflected in changes in food intake and BW. Abstract Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. View 2 excerpts, references results.

Introduction

Highly Influenced. Gertler and D. Endocrinology and Metabolism. Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension.

Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Other contributing factors may involve a shift in detain sensitivity triggered by hyperleptinemia and a decrease in energy expenditure. After removing faeces and woodshavings from the paper, food spillage was collected and weighed. After 8 weeks of high or low-fat diet, six mice from each group received an intraperitoneal i. High-fat diet treatment for 20 wk revealed that, compared with normal mice, the LepTg mice had an increased susceptibility to diet-induced obesity, as demonstrated by their rate of weight gain, higher accumulation of sc white adipose tissue mass, hypertrophy of adipocytes, and normalization of their reduced metabolic parameters.

ScienceDaily shares links with sites in the TrendMD network and earns revenue from third-party advertisers, where indicated. Quantitation of the ORO dye, a measure of triglyceride content of differentiated adipocytes, revealed that the LepTg adipocytes had accumulated 4. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil red O. Discussion The results presented here show that mice exposed to a high-fat diet for 19 weeks develop obesity and, progressively, peripheral and then central leptin insensitivity. Issue Date : 01 May

Publication types

Related articles endogenou Web of Science Google Scholar. The efficacy of such murine monogenic models of obesity in determining the mechanisms underlying human obesity remains to be seen. Although the low levels of insulin and IGF-1 in the LepTg mice on the CFD may be secondary to their phenotype, they could fail to promote a favorable environment for preadipocyte differentiation and triacylglycerol accumulation. Google Scholar.

Nature genetics. Publication Type. Search articles by 'Lee Ann Norman'. Thus, persistance of obesity in DIO mice occurs despite ongoing endogenous leptin action. Smart citations by scite. The melanocortin system plays a critical role mediating the effect of leptin on food intake and BW Seeley et al.

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Does leptin cause an increase in blood pressure in animals and humans? Has PDF. Mol Metab6 1024 Jun Abstract Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. Paper Mentions. Development and characterization of high affinity leptins and leptin antagonists. Figures and Topics from this paper.

Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in muce mouse. Either your web browser doesn't support Javascript or it is currently turned off. T-tests were used for comparison of two groups and two-way ANOVA with or without repeated measures and Sidak multiple comparison tests were used for post hoc comparisons. Funding Funders who supported this work.

Thus, although the increase in baseline Socs3 levels exhibited by DIO mice may attenuate the effect of exogenously administered leptin, explaining the lack of expected hypophagia or activation of LEPR signaling cascade, our results suggest that DIO mice do not experience reduced endogenous leptin action, and in fact demonstrate that it plays a critical role preventing further BW gain. Ottaway N 1. Similar Articles To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation. The inability of high endogenous leptin levels to reduce feeding and mitigate or reverse weight gain is referred as leptin resistance and it has been implicitly associated to the impairment of leptin action Myers et al. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

One proposed mechanism of leptin resistance involves reduced LEPR signaling as a result of increased S ocs3 levels Bjorbaek et al. Suppression of leptin and insulin signaling by SOCS3 opens in new tab. Obesity Mice, Obese Melanocortin 4 Receptor 3,3'-dipropyloxadicarbocyanine leptin receptor. View 6 excerpts, references background.

Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse. Fluorescent blood-brain barrier tracing shows intact leptin transport in obese mice. Since leptin receptor antagonism reduced Socs3 gene expression, p-STAT3 levels, and the expression of a target gene, Pomc Munzberg et al. Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese DIO mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. UC-led obesity research finds leptin hormone isn't the overeating culprit. Similar Articles To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

  • Increased hypothalamic protein tyrosine phosphatase 1B contributes to leptin resistance with age.

  • Correspondence to XF Huang.

  • New insights in leptin resistance mechanisms in mice. View on PubMed.

  • The Medical News. Acute disruption of leptin signaling in vivo leads to increased insulin levels and insulin resistance.

Save to Library Save. The Journal of endocrinology. Leptin antagonist reverses hypertension caused by leptin overexpression, but fails to normalize obesity-related hypertension. Smart citations by scite. Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies.

Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF Leptin antagonist reverses hypertension caused by leptin overexpression, but fails to normalize obesity-related hypertension. A comment on this article appears in " Leptin keeps working, even in obesity. Rivero B 2. View 2 excerpts, cites background.

Associated Data

These findings lepttin that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice. Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Front Immunol, 18 Jun

Wang, F. To dist the biological actions of leptin in a physiological context, we 7 and others 8 have recently generated transgenic mice oversecreting leptin LepTg. Tartaglia LA The leptin receptor. Diabetes 37 : — Revised : 08 November After removing faeces and woodshavings from the paper, food spillage was collected and weighed. Thus, it is likely that a similar mechanism may interfere with the central action of leptin in HFD-fed LepTg mice.

View 3 excerpts, references background. More Filters. Highly Influenced. This approach was taken with genetic and diet-induced models of obese mice. View 2 excerpts, cites background. Renaissance of leptin for obesity therapy.

T-tests were used for comparison of two groups and two-way Inducsd with or without repeated measures and Sidak multiple comparison tests were used for post hoc comparisons. This increased potency, combined with the extended duration of action provided by the addition of a polyethylene glycol moiety, provides effectiveness to PLA when admistered peripherally, results that are consistent with earlier reports Chapnik et al. Copyright notice. View 7 excerpts, references background.

Search articles by 'David A D'Alessio'. Reprogramming the body weight set point by a reciprocal interaction of hypothalamic leptin sensitivity and Pomc gene expression reverts extreme obesity. Funding Funders who supported this work. Abstract Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin.

After 8, 15 and 19 weeks feeding, body weight gain of the HFF group edogenous Google Scholar. D Effects of i. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Food consumption measurement Food consumption was estimated by subtracting the amount of food left in the plastic dishes and the amount of food spilled from the initial food weight.

Search Search articles by subject, keyword or author. Although eetain leptin infusions in normal mice have resulted in an increase in energy expenditure 14diet induced obese mice retain endogenous leptin action and it would be logical to assume the same for the LepTg mice, the effect of a chronic response to hyperleptinemia on energy expenditure has not yet been determined. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. From 8 weeks, however, the energy intake of the HFF group began a gradual increase; then, at approximately 15 weeks, it increased dramatically, surpassing that of the LFF mice, and after 19 weeks of feeding, was Email alerts Article activity alert.

This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. In the latter case, please turn on Javascript support in your web browser and reload this page. Nature reviews. Mahbod P 1. This discrepancy suggests an age-dependent convergence from multiple neural circuits towards the melanocortin system as the mediator of leptin effects on the homeostatic control of energy balance.

Leptin and Obesity: Role and Clinical Implication. Peptides30 723 Apr I agree, dismiss this banner. Front Immunol, 18 Jun

The relatively modest effect of leptin to reduce body weight acgion obese humans may be due to the limited benefit of increasing leptin levels in already hyperleptinemic subjects Heymsfield et al. Impaired leptin responsiveness in aged rats. Identifying the factors involved in counteracting the effect of leptin during the development of obesity may provide efficacious targets to prevent BW gain. Thus, mechanisms opposing leptin must play a crucial role in the development or maintenance of obesity. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese DIO mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. Hypothalamic melanocortin signaling and leptin resistance--perspective of therapeutic application for obesity-diabetes syndrome.

Norman LA 1. Cited by: 3 articles PMID: I agree, dismiss this banner.

Search articles by 'David A D'Alessio'. Identification of SOCS-3 as a potential mediator of central leptin resistance. Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF Challenges and opportunities of defining clinical leptin resistance. Journal of peptide science : an official publication of the European Peptide Society. This approach was taken with genetic and diet-induced models of obese mice. These findings demonstrate that hyperleptinemic DIO mice retain leptin-suppression of feeding comparable to lean mice, and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice.

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Histological examination of WAT Fig. We found that, compared with diet induced obese mice retain endogenous leptin action mice, the small adipose mass of the LepTg mice had an increased cellularity, which resulted in substantial accumulation of triacylglycerols as evidenced by ORO staining Fig. High-fat diet treatment lptin 20 wk revealed that, compared with normal mice, the LepTg mice had an increased susceptibility to diet-induced obesity, as demonstrated by their rate of weight gain, higher accumulation of sc white adipose tissue mass, hypertrophy of adipocytes, and normalization of their reduced metabolic parameters. Receive exclusive offers and updates from Oxford Academic. Email alerts Article activity alert. Figure 3. Computation of the slope of the increase in body weight of each mouse revealed that the body weight gain of the LepTg mice was 1.

Leptin levels reflect lipid content in inducee evidence for diet-induced resistance to leptin action Nature Med 1 : — Science : — Additional studies will be needed to define the role of GH with respect to IGF-1 in animals chronically responsive to hyperleptinemia. Research led by investigators at the University of Cincinnati UC Metabolic Diseases Institute, however, found that leptin action isn't the culprit. Lin S, Huang XF.

PLA was dosed based on BW 1. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Thus, persistance of obesity in DIO mice occurs despite ongoing endogenous leptin action.

A longitudinal assessment of energy expenditure of the LepTg mice on the HFD will reveal the extent to which energy expenditure plays a role in the diet-induced obesity phenotype of the LepTg mice. Revised : 08 November In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Search ADS.

The Endogrnous of biological chemistry. Renaissance of leptin for obesity therapy. Onigata K. SOCS3 expression within leptin receptor-expressing cells regulates food intake and leptin sensitivity but does not affect weight gain in pregnant mice consuming a high-fat diet. While the resistance of obese subjects to exogenous leptin has been widely documented, the action of endogenous leptin to control energy balance in obesity has not been rigorously tested. Physiol Behav, 28 Jan

To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. Lephin Yoshimura. Cell Metab33 6 Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin. While the resistance of obese subjects to exogenous leptin has been widely documented, the action of endogenous leptin to control energy balance in obesity has not been rigorously tested.

  • Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk.

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Positional cloning of the mouse obese gene and its human homologue. Search articles by 'Arieh Gertler'. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism. Gertler and D.

Results Citations. Figure 2. Journal of hypertension. Cell Metab. Get PDF. Leptin and the maintenance of elevated body weight.

Nickki Ottaway Diego Perez-Tilve. Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse. This suggestion that our DIO mice have near maximal endogenous leptin action provides a caveat to the therapeutic application of leptin to treat obesity. Search articles by 'David A D'Alessio'. UC-led obesity research finds leptin hormone isn't the overeating culprit.

Journal of hypertension. Please note that during the production process errors may endogejous discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. American journal of physiology Endocrinology and metabolism. Acute disruption of leptin signaling in vivo leads to increased insulin levels and insulin resistance. Bace1-dependent amyloid processing regulates hypothalamic leptin sensitivity in obese mice.

Fluorescent blood-brain barrier tracing shows intact leptin transport in obese mice. CCK increases the transport of insulin into the brain. Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. Acute disruption of leptin signaling in vivo leads to increased insulin levels and insulin resistance. Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. Related Papers.

Icv LA significantly increased food intake Fig 3jsee also Fig. BW and energy intake were monitored daily. Read article at publisher's site DOI : Leptin and Obesity: Role and Clinical Implication.

Blood was drawn into heparinized tubes from the retro orbital sinus under Avertin anesthesia. The gain in inguinal fat mass of mie HFF group was not significantly greater than that of the LFF controls at 1 and 8 weeks feeding, and was Rights and permissions Reprints and Permissions. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. Publication types Research Support, N. Obesity research finds leptin hormone isn't the overeating culprit.

This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. Individuals lacking circulating leptin are hyperphagic and obese, features that can be reversed with administration of exogenous leptin Halaas et al. PloS one. Weight-reducing effects of the plasma protein encoded by the obese gene. Search articles by 'Belen Rivero'. Positional cloning of the mouse obese gene and its human homologue. This website requires cookies, and the limited processing of your personal data in order to function.

Obesity Mice, Obese Melanocortin 4 Receptor 3,3'-dipropyloxadicarbocyanine leptin receptor. Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. American journal of physiology Endocrinology and metabolism.

Our results suggest that DIO develops despite the sustained contribution actioh endogenous leptin to regulate energy balance. The observation that both lean and DIO mice had comparable increases in energy intake and BW that were proportional to the doses of antagonist administered peripherally or centrally, demonstrates that both groups experienced substantial restraint of food intake by endogenous leptin, irrespective of their body weight and adiposity. Daily injection of PLA increases energy intake aBW b and BW change c in lean chow-fed control mice but not in mice voided of endogenous leptin signaling. More Filters.

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LepTg HFD. The absorbance of the dye at nm was normalized to the amount of tissue used for the differentiation experiment and expressed as absorbance units per 10 mg of WAT. Needle diet induced obese mice retain endogenous leptin action was confirmed by visual examination of the lateral ventricle in the tissue sections. However, the effectors leading to a rapid accumulation of WAT mass must lie in the periphery, likely at the level of preadipocytes differentiation and accumulation of triacylglycerols in their small adipocytes. Although the low levels of insulin and IGF-1 in the LepTg mice on the CFD may be secondary to their phenotype, they could fail to promote a favorable environment for preadipocyte differentiation and triacylglycerol accumulation.

To directly determine endogenous leptin activity in obesity, we keptin lean and obese mice with a leptin receptor antagonist. Figure 3. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Loss of pericyte smoothened activity in mice with genetic deficiency of leptin. Positional cloning of the mouse obese gene and its human homologue.

CCK increases the transport of insulin into the brain. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. Impaired transport of leptin across leptln blood-brain barrier in obesity. We hypothesized that blockade of the LEPR in mouse models of obesity would give an estimate of endogenous leptin action reflected in changes in food intake and BW. Mechanisms of leptin action and leptin resistance. Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action. To circumvent any role of differences in BBB permeability between lean and obese mice, we compared peripheral and icv administration of high doses of LEPR antagonist.

In contrast, use of leptin during BW loss, when leptin levels drop and there is room for further LEPR activation, seems to be a much more effective approach Clemmensen et al. Copyright notice. BioStudies: supplemental material and supporting data.

The middle phase is perhaps the most fascinating. The extension and relevance of these findings to human obesity hint that, if a subset of individuals are lean because of increased leptin secretion, they may develop an abundance of preadipocytes and small adipocytes, which when exposed to rich-fat diets would undergo rapid differentiation and expansion resulting in severe obesity. Wang, F. Clinical Phytoscience View all the latest top news in the environmental sciences, or browse the topics below:. Related articles in Web of Science Google Scholar. To investigate the biological actions of leptin in a physiological context, we 7 and others 8 have recently generated transgenic mice oversecreting leptin LepTg.

In our studies this effect is comparable to the lean control mice. We thank Drs. The mice had free access to water and HFD overnight and were euthanized 1 h after the onset of light. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. New insights in leptin resistance mechanisms in mice.

As a service to our customers we are providing this early version of the manuscript. Overall, the findings presented here demonstrate comparable endogenous leptin activity in lean and obese hyperleptinemic diet-induced obese mice, despite different sensitivity to exogenously administered leptin. Galbraith Road. Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action.

LepTg CFD. Adipose tissue leptin production and plasma leptin kinetics in humans Diabetes 45 : — Figure 3.

Published : 31 May After 8, 15 and 19 weeks feeding, body weight gain of the HFF group was Wang, F. After 8 weeks of high or low-fat diet, six mice from each group received an intraperitoneal i. Adipocytes areas are expressed in pixels px. Download PDF.

  • Rivero B 2. Leptin is a 16kDa hormone secreted by adipocytes Zhang et al.

  • J Biol Chem : —

  • See other articles in PMC that cite the published article. Mahbod P 1 .

  • Hyperleptinemia is required for the development of leptin resistance.

However, despite the hypophagia, excess fat still accumulates with apparent gains in energetic efficiency at least partially thwarting this regulatory endeavour. D Effects of i. E Effects of i. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. After 1 week of high or low-fat diet, six mice from each group received an i.

Evidence is accumulating to suggest that this pathway is involved in mediating leptin effects on energy intake and body weight. Living Well. OgusS. The extension and relevance of these findings to human obesity hint that, if a subset of individuals are lean because of increased leptin secretion, they may develop an abundance of preadipocytes and small adipocytes, which when exposed to rich-fat diets would undergo rapid differentiation and expansion resulting in severe obesity.

A superactive leptin antagonist alters metabolism and locomotion in high-leptin mice. Consistent with this thesis, obese hyperleptinemic animals have a blunted anorectic response to exogenously administered leptin and an associated attenuation of the leptin receptor LEPR -dependent intracellular signaling cascade Enriori et al. Mol Metab6 1024 Jun Highly Influential.

Results Experiment 1: measurements axtion body weight, calorie intake, fat storage and plasma leptin in mice fed a high- or low-fat diet for 1, 8, 15 or 19 weeks A lepttin increase in body weight gain in mice fed the high-fat diet was evident after only 2 weeks of high-fat feeding, and this trend continued throughout the dietary protocol Figure 1A. C Effects of intracerebroventricular injection i. Ogus, Y. Prenatal androgen exposure alters KNDy neurons and their afferent network in a model of polycystic ovarian syndrome. Article Contents Abstract. Although short-term leptin infusions in normal mice have resulted in an increase in energy expenditure 1424 and it would be logical to assume the same for the LepTg mice, the effect of a chronic response to hyperleptinemia on energy expenditure has not yet been determined. There was no significant difference in tibia bone length between the two groups Figure 2E.

Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus Endocrinology : — The pharmacologic approach to the endogenoua of obesity J Clin Pharmac 37 : — Sign In or Create an Account. Received : 18 September To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer.

Abnormal splicing of the leptin receptor in diabetic mice Nature : — P CFD. OgusS. Peripheral, but not central, leptin insensitivity is evident by 8 weeks of HFF.

Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long-term energy homeostasis opens in new tab. More importantly, this occurred at doses of antagonist sufficient to elicit similar changes in energy intake and BW in lean and DIO mice. Recent Activity. Acute disruption of leptin signaling in vivo leads to increased insulin levels and insulin resistance. Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin signaling. The antagonist increased feeding and body weight BW in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency.

  • Loss of pericyte smoothened activity in mice with genetic deficiency of leptin.

  • The subsequent increase in insulin and IGF-1 from the HFD would then be consistent with increased adipocyte differentiation and triacylglycerols accumulation.

  • BioStudies: supplemental material and supporting data.

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Since leptin receptor antagonism reduced Socs3 gene expression, p-STAT3 levels, and the expression of a target gene, Pomc Munzberg et al. A comment on this article appears in " Leptin keeps working, even in obesity. Share this article Share with email Share with twitter Share with linkedin Share with facebook. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Create Alert Alert. Paper Mentions. Molecular and cellular biology.

Citation Type. This discrepancy suggests an age-dependent convergence mice retain multiple neural circuits towards the melanocortin system as the mediator actiom leptin effects on the homeostatic control of energy balance. Data that cites the article This data has been provided by curated databases and other sources that have cited the article. Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long-term energy homeostasis opens in new tab. A superactive leptin antagonist alters metabolism and locomotion in high-leptin mice. Drug discovery.

Development and characterization of high affinity leptins and leptin antagonists. Research Feed. Orexin A-induced inhibition of leptin expression and secretion in adipocytes reducing plasma leptin levels and hypothalamic leptin resistance.

Cell Metab33 6 Save to Library Save. Author information Copyright and License information Disclaimer. Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Leptin and Obesity: Role and Clinical Implication.

Akihiko Yoshimura. Leptin actioh a reversion of leptin-resistant states. PMID: Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Highly Influential. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. Publication Type.

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