The effect of leptin on trained innate immunity and on systemic inflammation in subjects with obesity.
| Title: | The effect of leptin on trained innate immunity and on systemic inflammation in subjects with obesity. |
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| Authors: | Gomez, Daniela Flores, Bekkering, Siroon, Horst, Rob ter, Cossins, Benjamin, Munckhof, Inge C L van den, Rutten, Joost H W, Joosten, Leo A B, Netea, Mihai G, Riksen, Niels P |
| Source: | Journal of Leukocyte Biology; Feb2024, Vol. 115 Issue 2, p374-384, 11p |
| Subject Terms: | NATURAL immunity, LEPTIN, MONONUCLEAR leukocytes, TUMOR necrosis factors, COMPULSIVE eating, SINGLE nucleotide polymorphisms, EXPOSURE therapy |
| Abstract: | Leptin is associated with cardiometabolic complications of obesity, such as metabolic syndrome and atherosclerosis. In obese men, the presence of metabolic syndrome is associated with higher circulating leptin and interleukin (IL)-6 concentrations and increased monocyte cytokine production capacity. Here, we investigated the effects of leptin on monocyte function and systemic inflammatory markers in obese individuals. We specifically explored whether leptin can induce long-term changes in innate immune function by inducing innate immune memory (also called trained immunity). We exposed human primary monocytes for 24 h to relevant leptin concentrations in vitro and measured cytokine production. In addition, after removing leptin, we incubated monocytes for 5 d in culture medium, and we restimulated them on day 6 to assess cytokine production capacity, phagocytosis, and foam cell formation. Direct stimulation with leptin did not induce cytokine production, but exposure to 50 ng/mL leptin augmented lipopolysaccharide- and R848-induced tumor necrosis factor α (TNF-α) production after 1 wk. In a separate in vivo study in a cohort of 302 obese subjects (body mass index [BMI] >27 kg/m2, 55 to 81 yr), we measured circulating leptin, inflammatory markers, and cytokine production upon ex vivo stimulation of isolated peripheral blood mononuclear cells. Circulating leptin concentrations positively correlated with circulating IL-1β and IL-6, which was more pronounced in men than in women. Four single nucleotide polymorphisms in the leptin gene influenced circulating IL-6 concentrations in men, suggesting a direct effect of leptin on IL-6. In conclusion, in vitro, leptin does not directly stimulate monocytes to produce cytokines, yet induces long-term monocyte hyperresponsiveness, i.e. trained immunity. In obese subjects, leptin is associated with circulating IL-6 in a sex-dependent manner. The underlying mechanisms of the sex-specific effect of leptin on innate immune cells remain to be further investigated. [ABSTRACT FROM AUTHOR] |
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| Database: | Complementary Index |
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| Items | – Name: Title Label: Title Group: Ti Data: The effect of leptin on trained innate immunity and on systemic inflammation in subjects with obesity. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Gomez%2C+Daniela+Flores%22">Gomez, Daniela Flores</searchLink><br /><searchLink fieldCode="AR" term="%22Bekkering%2C+Siroon%22">Bekkering, Siroon</searchLink><br /><searchLink fieldCode="AR" term="%22Horst%2C+Rob+ter%22">Horst, Rob ter</searchLink><br /><searchLink fieldCode="AR" term="%22Cossins%2C+Benjamin%22">Cossins, Benjamin</searchLink><br /><searchLink fieldCode="AR" term="%22Munckhof%2C+Inge+C+L+van+den%22">Munckhof, Inge C L van den</searchLink><br /><searchLink fieldCode="AR" term="%22Rutten%2C+Joost+H+W%22">Rutten, Joost H W</searchLink><br /><searchLink fieldCode="AR" term="%22Joosten%2C+Leo+A+B%22">Joosten, Leo A B</searchLink><br /><searchLink fieldCode="AR" term="%22Netea%2C+Mihai+G%22">Netea, Mihai G</searchLink><br /><searchLink fieldCode="AR" term="%22Riksen%2C+Niels+P%22">Riksen, Niels P</searchLink> – Name: TitleSource Label: Source Group: Src Data: Journal of Leukocyte Biology; Feb2024, Vol. 115 Issue 2, p374-384, 11p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22NATURAL+immunity%22">NATURAL immunity</searchLink><br /><searchLink fieldCode="DE" term="%22LEPTIN%22">LEPTIN</searchLink><br /><searchLink fieldCode="DE" term="%22MONONUCLEAR+leukocytes%22">MONONUCLEAR leukocytes</searchLink><br /><searchLink fieldCode="DE" term="%22TUMOR+necrosis+factors%22">TUMOR necrosis factors</searchLink><br /><searchLink fieldCode="DE" term="%22COMPULSIVE+eating%22">COMPULSIVE eating</searchLink><br /><searchLink fieldCode="DE" term="%22SINGLE+nucleotide+polymorphisms%22">SINGLE nucleotide polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22EXPOSURE+therapy%22">EXPOSURE therapy</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Leptin is associated with cardiometabolic complications of obesity, such as metabolic syndrome and atherosclerosis. In obese men, the presence of metabolic syndrome is associated with higher circulating leptin and interleukin (IL)-6 concentrations and increased monocyte cytokine production capacity. Here, we investigated the effects of leptin on monocyte function and systemic inflammatory markers in obese individuals. We specifically explored whether leptin can induce long-term changes in innate immune function by inducing innate immune memory (also called trained immunity). We exposed human primary monocytes for 24 h to relevant leptin concentrations in vitro and measured cytokine production. In addition, after removing leptin, we incubated monocytes for 5 d in culture medium, and we restimulated them on day 6 to assess cytokine production capacity, phagocytosis, and foam cell formation. Direct stimulation with leptin did not induce cytokine production, but exposure to 50 ng/mL leptin augmented lipopolysaccharide- and R848-induced tumor necrosis factor α (TNF-α) production after 1 wk. In a separate in vivo study in a cohort of 302 obese subjects (body mass index [BMI] >27 kg/m<superscript>2</superscript>, 55 to 81 yr), we measured circulating leptin, inflammatory markers, and cytokine production upon ex vivo stimulation of isolated peripheral blood mononuclear cells. Circulating leptin concentrations positively correlated with circulating IL-1β and IL-6, which was more pronounced in men than in women. Four single nucleotide polymorphisms in the leptin gene influenced circulating IL-6 concentrations in men, suggesting a direct effect of leptin on IL-6. In conclusion, in vitro, leptin does not directly stimulate monocytes to produce cytokines, yet induces long-term monocyte hyperresponsiveness, i.e. trained immunity. In obese subjects, leptin is associated with circulating IL-6 in a sex-dependent manner. The underlying mechanisms of the sex-specific effect of leptin on innate immune cells remain to be further investigated. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Journal of Leukocyte Biology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1093/jleuko/qiad118 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 11 StartPage: 374 Subjects: – SubjectFull: NATURAL immunity Type: general – SubjectFull: LEPTIN Type: general – SubjectFull: MONONUCLEAR leukocytes Type: general – SubjectFull: TUMOR necrosis factors Type: general – SubjectFull: COMPULSIVE eating Type: general – SubjectFull: SINGLE nucleotide polymorphisms Type: general – SubjectFull: EXPOSURE therapy Type: general Titles: – TitleFull: The effect of leptin on trained innate immunity and on systemic inflammation in subjects with obesity. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Gomez, Daniela Flores – PersonEntity: Name: NameFull: Bekkering, Siroon – PersonEntity: Name: NameFull: Horst, Rob ter – PersonEntity: Name: NameFull: Cossins, Benjamin – PersonEntity: Name: NameFull: Munckhof, Inge C L van den – PersonEntity: Name: NameFull: Rutten, Joost H W – PersonEntity: Name: NameFull: Joosten, Leo A B – PersonEntity: Name: NameFull: Netea, Mihai G – PersonEntity: Name: NameFull: Riksen, Niels P IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 02 Text: Feb2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 07415400 Numbering: – Type: volume Value: 115 – Type: issue Value: 2 Titles: – TitleFull: Journal of Leukocyte Biology Type: main |
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