Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome

Kuo, Lydia E; Kitlińska, Joanna; Tilan, Jason U.; Li, Lijun; Baker, Stephen B.; Johnson, Michael D.; Lee, Edward W.; Burnett, Mary Susan; Fricke, Stanley T.; Květňanský, Richard; Herzog, Herbert; Żukowska, Zofia

doi:10.1038/nm1611

Cited by 584 publications

(557 citation statements)

References 43 publications

Supporting

Mentioning

499

Contrasting

Unclassified

Order By: Relevance

“…In mice, social aggression stress increased NPY release by sympathetic nerves and this, in turn, promoted the development of abdominal obesity through specifically upregulating and activating NPY receptors (NPY2R) on abdominal WAT, and stimulating angiogenesis, macrophage infiltration and adipocyte differentiation in this tissue. 49 Importantly, these effects were only seen in the combined presence of stress and a high-fat diet. Since NPY2R are expressed in human WAT, it would be interesting to further investigate this pathway in humans.…”

Section: Discussionmentioning

confidence: 99%

Stress-induced cytokine responses and central adiposity in young women

et al. 2007

View full text Add to dashboard Cite

Background: Evidence suggests that people who are more responsive to psychological stress are at an increased risk of developing obesity. However, the biological mechanisms underlying this phenomenon are poorly understood. The cytokines leptin, interleukin-1 receptor antagonist (IL-1Ra) and interleukin-6 (IL-6) play a key role in fat metabolism and abnormal circulating levels of these proteins have been reported in obese people and in individuals subject to stress. Objective: This study investigated whether cytokine responses to acute mental stress are associated with adiposity in healthy young women. Design and Subjects: A laboratory study of 67 women, aged 18-25 years, recruited from University College London. Measurements: Height, weight and waist circumference were measured and body fat mass was estimated by bioelectrical impedance body composition analysis. Laboratory mental stress testing was carried out and blood pressure and heart rate were recorded at baseline, during two moderately challenging tasks (Stroop and speech) and during recovery 40-45 min post-stress. Blood samples taken at baseline, immediately post-stress and 45 min post-stress, were used for assessment of circulating cytokines. Saliva samples taken throughout the session were assessed for cortisol. Results: Women who had larger cytokine responses to stress were more abdominally obese than women with smaller cytokine stress responses. Specifically, there was a positive correlation between waist circumference and stress-induced increases in plasma levels of leptin (r ¼ 0.35, Po0.05) and IL-1Ra responses (r ¼ 0.29, Po0.05). There was also a significant positive correlation between prolonged diastolic blood pressure responses to stress and measures of total and abdominal obesity (r ¼ 0.28-0.33, Po0.05). Conclusion: Increased cytokine production could be a mechanism linking stress and abdominal obesity.

show abstract

Section: Discussionmentioning

confidence: 99%

Stress-induced cytokine responses and central adiposity in young women

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Adverse psychosocial factors stimulate the hypothalamuspituitary-adrenal axis and the sympathetic nervous system, resulting in increased release of cortisol, adrenaline (epinephrine) and neuropeptide Y. Cortisol is a stress hormone that triggers glucose production, increases lipolysis and circulating NEFA, decreases insulin secretion from beta cells and decreases sensitivity to insulin [41,42]. Adrenaline has similar effects to cortisol on glucose and fat metabolism [41,42], and neuropeptide Y may mediate stress-induced obesity and the metabolic syndrome by increasing adipogenesis and lipolysis [43], thereby resulting in poor control of diabetes.…”

Section: Discussionmentioning

confidence: 99%

An association of adverse psychosocial factors with diabetes mellitus: a meta-analytic review of longitudinal cohort studies

2008

View full text Add to dashboard Cite

Aims/hypothesis There has been substantial interest in the association between psychosocial stress and risk of diabetes mellitus, but no data on the systematic quantification of the causal relationship have been published. This analysis aims to evaluate the association between adverse psychosocial factors and diabetes mellitus. Methods We performed a search of Medline, PsycINFO, Web of Science and PubMed up to July 2008. The studies included were prospective cohort studies investigating the association between adverse psychosocial factors and risk of diabetes mellitus. Results There were 22 relationships between psychosocial factors and disease-related factors (in 14 papers), of which 16 evaluated the associations of adverse psychosocial factors with diabetes control in diabetic populations and six evaluated the associations of adverse psychosocial factors with the incidence of diabetes in populations without any diagnosed diabetes. The overall meta-analysis demonstrated that adverse psychosocial factors were significantly associated with poor diabetes control (combined correlation coefficient, r=0.096, p=0.006), whereas adverse psychosocial factors were not associated with incident diabetes mellitus. More notably, sensitivity analyses showed that low social support was more robustly associated with poor diabetes control than stressful events per se or stress-prone personality or coping style, and that adverse psychosocial factors were associated with poor control of type 1 and type 2 diabetes. Conclusions/interpretation The current review revealed a detrimental association of psychosocial factors with the prognosis of both type 1 and type 2 diabetes. However, any aetiological effect of adverse psychosocial factors remains elusive as a result of the small number of individuals enrolled in the cohorts studied.

show abstract

“…(14) Y1 (34) and Y2 (35) receptors expressed on adipocytes have been shown to play a role in preadipocyte proliferation and differentiation. Therefore, we used BMSC cultures to examine whether the Y1 receptor also plays a role in the differentiation of adipocytes within the bone microenvironment.…”

Section: Lack Of the Y1 Receptor Increases In Vitro Adipocyte Formatimentioning

confidence: 99%

Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity

Lee

Doyle

Sainsbury

et al. 2010

Journal of Bone and Mineral Research

Self Cite

103

135

View full text Add to dashboard Cite

The neuropeptide Y (NPY) system has been implicated in the regulation of bone homeostasis and osteoblast activity, but the mechanism behind this is unclear. Here we show that Y1 receptor signaling is directly involved in the differentiation of mesenchymal progenitor cells isolated from bone tissue, as well as the activity of mature osteoblasts. Importantly, the mRNA levels of two key osteogenic transcription factors, runx2 and osterix, as well as the adipogenic transcription factor PPAR-g, were increased in long bones of Y1 À/À mice compared with wild-type mice. In vitro, bone marrow stromal cells (BMSCs) isolated from Y1 À/À mice formed a greater number of mineralized nodules under osteogenic conditions and a greater number of adipocytes under adipogenic conditions than controls. In addition, both the number and size of fibroblast colony-forming units formed in vitro by purified osteoprogenitor cells were increased in the absence of the Y1 receptors, suggestive of enhanced proliferation and osteogenesis. Furthermore, the ability of two specific populations of mesenchymal progenitor cells isolated from bone tissue, an immature mesenchymal stem cell population and a more committed osteoprogenitor cell population, to differentiate into osteoblasts and adipocytes in vitro was enhanced in the absence of Y1 receptor signaling. Finally, Y1 receptor deletion also enhanced the mineral-producing ability of mature osteoblasts, as shown by increased in vitro mineralization by BMSCs isolated from osteoblast-specific Y1 À/À mice. Together these data demonstrate that the NPY system, via the Y1 receptor, directly inhibits the differentiation of mesenchymal progenitor cells as well as the activity of mature osteoblasts, constituting a likely mechanism for the high-bone-mass phenotype evident in Y1 À/À mice. ß

show abstract

Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome

Cited by 584 publications

References 43 publications

Stress-induced cytokine responses and central adiposity in young women

Stress-induced cytokine responses and central adiposity in young women

An association of adverse psychosocial factors with diabetes mellitus: a meta-analytic review of longitudinal cohort studies

Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity

Contact Info

Product

Resources

About