Leptin regulates CD16 expression on human monocytes in a sex‐specific manner

Physiological Reports

Joseph G. Cannon²  Gyanendra Sharma¹  Gloria Sloan²  Christiana Dimitropoulou¹  R. Randall Baker²  Andrew Mazzoli²  Barbara Kraj²  Anthony Mulloy¹ 

[1]Medical College of Georgia, Georgia Regents University, Augusta, Georgia

[2]College of Allied Health Sciences, Georgia Regents University, Augusta, Georgia

关键词: Blood pressure;    carotid compliance;    intima‐media thickness;    leptin receptor;   

DOI  :  10.14814/phy2.12177

来源: Wiley

【 摘 要 】

Abstract

Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic-sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16-positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16-positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14⁺⁺16⁺⁺ monocytes, which are primary producers of TNFα, were positively related to plasma leptin concentrations (P < 0.0001), with a stronger correlation in men (P < 0.05 for leptin × sex interaction). In vitro, recombinant human leptin induced CD16 expression in a dose-related manner (P = 0.02), with a stronger influence on monocytes from men (P = 0.03 for leptin × sex interaction). There were no sex-related differences in total leptin receptor expression on any monocyte subtypes, relative expression of long versus short isoforms of the receptor, or soluble leptin receptor concentrations in the plasma. The number of circulating CD14⁺16⁺⁺ monocytes, which preferentially migrate into nascent plaques, was positively related to systolic blood pressure (R = 0.56, P = 0.0008) and intima-media thickness (R = 0.37, P = 0.03), and negatively related to carotid compliance (R = −0.39, P = 0.02). These observations indicate that leptin promotes the development of CD16-positive monocyte populations in a sex-specific manner and that these subpopulations are associated with diminished vascular function.

【 授权许可】

CC BY   
© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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