Effects of Physiological Leptin Administration on Markers of Inflammation, Platelet Activation, and Platelet Aggregation during Caloric Deprivation

Canavan, Bridget; Salem, Raneem O.; Schurgin, Sunita; Koutkia, Polyxeni; Lipinska, Izabella; Laposata, Michael; Grinspoon, Steven

doi:10.1210/jc.2005-0780

Cited by 93 publications

(62 citation statements)

References 28 publications

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“…Leptin-induced platelet aggregation is blunted, but not completely abolished, in overweight and obese patients when compared to normal weight subjects, and this observation suggests that leptin receptor on platelet membrane may represent a site of leptin resistance in human obesity. 19 These findings have been recently extended by Canavan et al 39 by demonstrating that normal weight subjects undergoing complete caloric deprivation had greater sensitivity in hemostatic responses to leptin. The present study further confirms the existence of a differential sensitivity to the pro-thrombotic action of leptin effect based on total adiposity, and suggests the hypothesis that platelet resistance to leptin in overweight or obese patients could represent a finalistic protective mechanism against the excess pro-thrombotic stimulation that would be produced by obesity-related hyperleptinemia.…”

Section: Discussionmentioning

confidence: 64%

“…Finally, the cross-sectional design does not allow us to verify whether leptin-dependent platelet aggregation increases with weight loss, improvement of leptin sensitivity and reduced leptin levels. Although in normal weight subjects caloric deprivation produce a greater hemostatic Metabolic syndrome and platelet response to leptin F Corica et al responses to leptin, 39 this finding need to be prospectively replicated in overweight and obese patients.…”

Section: Discussionmentioning

confidence: 99%

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Relationship between metabolic syndrome and platelet responsiveness to leptin in overweight and obese patients

et al. 2006

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Objective: To verify whether platelet responsiveness to leptin is associated with metabolic syndrome risk factors. Design: Cross-sectional study. Subjects: We studied 169 consecutive patients, mean age ¼ 43.679.9 years, with overweight (N ¼ 57) or obesity (N ¼ 112). Measurements: Cluster analysis was used to generate three clusters based on platelet responsiveness to increasing doses of leptin. Profiles of metabolic syndrome risk factors of the three clusters were compared by discriminant analysis. Results: Platelet responsiveness to leptin was absent in cluster 1, whereas cluster 3 had the greatest platelet aggregation response to leptin pre-incubation. Plasma leptin levels significantly decreased from cluster 1 to cluster 3 in both gender. Patients in cluster 2 had an intermediate profile of leptin responsiveness. Highest body mass index (BMI) values were more frequent in non-responders, whereas the prevalence of high waist circumference, as well as hypertriglyceridemia and hypertension, increased with increasing responsiveness to leptin from cluster 1 to cluster 3. Pattern of metabolic syndrome risk factors qualified as group specific in 69.0% of the cluster 1, 54.9% of the cluster 2 and 55.8% of the cluster 3. Circulating leptin, waist circumference, plasma triglycerides and BMI defined distinctive patterns of metabolic syndrome risk factors in the clusters. Conclusions: In overweight and obese outpatients, metabolic syndrome risk factors parallel to some extent platelet responsiveness to leptin. Such a correlation involves plasma leptin levels, waist circumference, plasma triglycerides and BMI, and may contribute to the excess risk of cardiovascular events in overweight and obese patients.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Relationship between metabolic syndrome and platelet responsiveness to leptin in overweight and obese patients

et al. 2006

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“…We have previously performed interventional studies in normo-or hyperleptinaemic lean and obese men and women, demonstrating that increasing leptin levels, through leptin administration, did not result in any significant change in several inflammatory markers associated with CVD in both short-term (3 days) and longer-term (16 weeks) studies [11]. In contrast, in human studies involving leptin administration in low leptin states, including congenital leptin deficiency and starvationinduced hypoleptinaemia, leptin administration was associated with a significant increase in inflammatory markers and increased platelet aggregation [3,10]. On the basis of the differing biological activity of leptin in low vs high leptin states the association with inflammatory biomarkers in obesity, a hyperleptinaemic leptin-resistant state, does not appear to be causal.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, although interventional studies in humans have shown that leptin administration in low leptin states is associated with increased inflammatory and platelet responses [3,10], there appears to be no significant effect of leptin administration in leptin-replete states such as obesity [11].…”

Section: Introductionmentioning

confidence: 99%

Circulating leptin levels are not associated with cardiovascular morbidity and mortality in women with diabetes: a prospective cohort study

Brennan

Kelesidis

et al. 2007

Diabetologia

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Aims/hypothesis Leptin, an adipocyte-secreted hormone, plays an important role in regulating neuroendocrine and immune function as well as insulin resistance and metabolism. Our objective was to examine the relationship between leptin levels and cardiovascular morbidity and overall mortality in women with type 2 diabetes. Subjects and methods This prospective cohort study included 1,194 women with a confirmed diagnosis of type 2 diabetes, who provided a blood sample at baseline in 1989-1990. Participants were followed for 12 years for the development of health outcomes including cardiovascular disease (CVD) events as well as total mortality. Results There were 218 new CVD events and 228 deaths from all causes. Cox proportional hazards analysis was used to estimate the relative risks (RRs) for each quintile level of leptin compared with the lowest quintile. Leptin levels were positively associated with several CVD risk factors including BMI and inflammatory markers, but were not independently associated with the incidence of CVD or total mortality in women with diabetes. The multivariate RRs (95% CIs) for CVD across the quintiles of leptin were 0.96 (0.61-1.53), 0.99 (0.61-1.61), 1.04 (0.63-1.71), 1.02 (0.59-1.75) (p for trend = 0.83). Conclusions/interpretation Although circulating leptin levels are associated with obesity and inflammatory markers, they are not significantly related to the risk of CVD or mortality in women with diabetes.

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“…Leptin levels are correlated with circulating levels of CRP, 30 and exogenous leptin increases CRP levels in normal-weight subjects but not in obese subjects, 31 and CRP decreases markedly during fasting-induced hypoleptinaemia. 32 The known direct proatherogenic effects of CRP 33 may thus be partly regulated by leptin. Leptin interacts with lipid metabolism at several levels: by stimulating macrophages to secrete lipoprotein lipase in the vessel wall; 34 by increasing the accumulation of cholesterol esters in foam cells, especially during hyperglycaemia 6 and by lowering HDL through increased clearance consequent on the upregulation of the scavenger receptor.…”

Section: 23mentioning

confidence: 99%

Leptin, but not adiponectin, is a predictor of recurrent cardiovascular events in men: results from the LIPID study

et al. 2008

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Objective: To investigate the relationships between plasma leptin and adiponectin levels and recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes. Design, subjects and measurements: A nested case-control study examined circulating leptin and adiponectin levels in plasma obtained 4-6 years after entry into the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial. Plasma was assayed from 184 men who suffered recurrent events within 4.4 years after blood collection and 184 matched controls who remained free of further events. The association between cardiovascular events and the explanatory variables was examined by conditional logistic regression analysis. Results: Relative risk (RR) increased across increasing leptin quartiles; the highest quartile compared with the lowest quartile was related to the highest risk (P for trend ¼ 0.002); the increased risk remained after adjustment for risk factors (P ¼ 0.018) or for obesity (P ¼ 0.038), but in the final model (adjusted for randomized treatment, other drugs, LIPID risk score, age and body mass index), the risk was attenuated (RR ¼ 1.61, 95% CI: 0.72-3.57, P for trend ¼ 0.34). Adiponectin did not predict cardiovascular events. Subjects randomly allocated to pravastatin had 6% lower leptin levels (P ¼ 0.04) than those allocated to placebo. Conclusion: Plasma leptin was a significant and independent predictor of recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes.

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Effects of Physiological Leptin Administration on Markers of Inflammation, Platelet Activation, and Platelet Aggregation during Caloric Deprivation

Abstract: Our data provide evidence that physiological leptin administration stimulates inflammatory and platelet responses in humans during caloric deprivation.

Cited by 93 publications

References 28 publications

Relationship between metabolic syndrome and platelet responsiveness to leptin in overweight and obese patients

Relationship between metabolic syndrome and platelet responsiveness to leptin in overweight and obese patients

Circulating leptin levels are not associated with cardiovascular morbidity and mortality in women with diabetes: a prospective cohort study

Leptin, but not adiponectin, is a predictor of recurrent cardiovascular events in men: results from the LIPID study

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