High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids

McMahon, Maureen; Skaggs, Brian J.; Sahakian, Lori; Grossman, Jennifer; Fitzgerald, John; Ragavendra, Nagesh; Charles‐Schoeman, Christina; Chernishof, Marissa; Gorn, Alan; Witztum, Joseph L.; Wong, Weng Kee; Weisman, Michael H.; Wallace, Daniel J.; Cava, Antonio La; Hahn, Bevra H.

doi:10.1136/ard.2010.142737

Cited by 141 publications

(96 citation statements)

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“…Although we and others have shown that leptin levels are elevated in SLE patients (5,6), it is not known whether the abnormal levels of this adipocytokine in SLE could be secondary to the chronic inflammatory state of the disease and/or directly contribute to its development.…”

mentioning

confidence: 99%

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Lourenço

Liu

Matarese

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptinsufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F 1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.systemic lupus erythematosus | leptin | autoimmunity | immune regulation | animal models

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mentioning

confidence: 99%

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Lourenço

Liu

Matarese

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…В ряде исследований высокие уровни лептина были связаны с риском субклинического атеросклероза у женщин [29,30].…”

Section: Discussionunclassified

Risk Prediction for Subclinical Atherosclerotic Lesion of Brachiocephalic Arteries in Obese Women

Шенкова¹,

Веселовская²,

Чумакова³

et al. 2017

Russ J Cardiol

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54Заболеваемость и смертность от сердечно-сосудис тых заболеваний (ССЗ) занимает первое место во многих странах мира, в том числе и в России [1]. Поэтому профилактика ССЗ, особенно в группах высокого риска, является приоритетным направле-нием современной кардиологии.Одна из таких групп высокого риска -пациенты с ожирением. Женщины, как правило, имеют более высокую степень ожирения на протяжении всей жизни, этот фактор риска (ФР) у женщин имеет боль-шое социальное значение, так как связан с наруше-нием репродуктивного здоровья, осложнением тече-ния беременности и возможной неонатальной забо-леваемостью [2,3]. Ряд исследований свидетельствуют о высокой встречаемости субклинического атеро-склероза магистральных артерий среди бессимптом- Шенкова Н. Н. -врач-кардиолог, Веселовская Н. Г. -д. м.н., зав. кардиологи-ческим отделением № 4, Алтайского краевого кардиологического диспансера, с. н.с. отдела мультифокального атеросклероза, Чумакова Г. А.* -д. м.н., про-фессор кафедры терапии и общей врачебной практики ФПК и ППС, в. н.с. отдела мультифокального атеросклероза, Осипова Е. С. -спирант кафедры терапии и общей врачебной практики ФПК и ППС, Гриценко О. В. -к. м.н., врач-кардиолог, Отт А. В. -врач-кардиолог Алтайского краевого кардиологи-ческого диспансера. ПРОГНОЗИРОВАНИЕ РИСКА СУБКЛИНИЧЕСКОГО АТЕРОСКЛЕРОЗА БРАХИОЦЕФАЛЬНЫХ АРТЕРИЙ У ЖЕНЩИН С ОЖИРЕНИЕМ*Автор, ответственный за переписку (Corresponding author): g. a.chumakova@mail.ru ССЗ -сердечно-сосудистые заболевания, ФР -факторы риска, ИБС -ише-мическая болезнь сердца, ЭЖТ -эпикардиальная жировая ткань, ВЖТ -вис-церальная жировая ткань, БЦА -брахиоцефальные артерии, СД -сахарный диабет, ИМТ -индекс массы тела, ТКИМ -толщина комплекса интима медиа, АБ -атеросклеротическая бляшка, САД -систолическое артериальное дав-ление, ОИМ -острый инфаркт миокарда, тЭЖТ -толщина эпикардиальной жировой ткани, ВО -висцеральное ожирение. Aim. To reveal the complex of metabolic risk factors, most significantly related to subclinical atherosclerosis of brachiocephalic arteries (BCA) in obese women. Material and methods. Totally, 89 women included, at the age 25-59 y. o. (50,6±6,6 y. o.) with abdominal obesity -waist circumference >80 cm with no clinical signs of coronary heart disease and atherosclerosis of other localizations. All women underwent duplex DCA scanning with the intima-media thickness assessment (IMT). Also, the main metabolic risk factors were assessed, adipokines of visceral fat tissue, ghrelin. Epicardial fat thickness (tEFT) in millimeters was measured by echo. Veloergometry was performed, to rule out angina and silent myocardial ischemia; cardiovascular risk assessment by SCORE, Framingham, PROCAM. Results. In 32,6% women there were signs of BCA atherosclerosis (IMT more than 1,3-1,5 mm). An equation was invented for logistic regression with the most significant predictors group (ghrelin, CRP, tEFT, leptin), related to subclinical BCA atherosclerosis in obese women, with sensitivity 89,7%. Conclusion. The complex of RF that were collected, might be used in clinical p...

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“…This aspect, together with the observation that leptin concentration is abnormally elevated in autoimmune mice and in patients affected by autoimmune disease [6] , led to wonder whether certain gene polymorphisms in SLE patients could contribute to the pathogenesis of the disease [3,7] . Additionally, past studies indicated an abnormal increase in serum/plasma leptin levels in SLE patients (independent of disease activity) [8][9][10][11][12] .…”

Section: Why Leptin and Slementioning

confidence: 99%

Leptin-related polymorphisms and SLE

Cava

2016

Inflamm Cell Signal

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Leptin is a hormone/cytokine that is mainly produced by adipocytes and has a range of actions that span from the control of metabolic balance to the modulation of adaptive and innate immune responses. Many investigations have indicated that the pro-inflammatory activities of leptin can contribute significantly to the promotion and maintenance of autoimmune responses. It is not known whether the abnormal elevation of leptin in patients with systemic lupus erythematous (SLE) -an autoimmune disease characterized by multi-organ involvement and the presence of autoantibodies -can reflect the chronic inflammatory status of the disease or can contribute to the pathogenesis of the disease. To partly address this question, a recent investigation analyzed several leptin-related gene polymorphisms in SLE in large numbers of individuals from different ancestral groups. The study identified weak associations with certain SNPs that did not remain significant after correction for multiple testing. This review discusses the implications of those findings for the pathogenesis of SLE and for the possibility of leptin-based modalities of therapeutic intervention in the disease.

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High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids

Cited by 141 publications

References 47 publications

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Risk Prediction for Subclinical Atherosclerotic Lesion of Brachiocephalic Arteries in Obese Women

Leptin-related polymorphisms and SLE

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