Research ArticleWeight-dependent changes of immune system in adipose tissue: Importance of leptin
Introduction
Emerging view leads to the proposition that obesity can be considered as states of chronic low-grade inflammation [1], [2], [3], [4], [5]. Indeed, the presence of numerous macrophages inside fat deposit and the alterations in their number in obesity have been shown [6], [7], [8], [9]. Furthermore, markers of inflammation such as TNFα, IL-6 and C reactive protein are increased in obesity and might predict the development of type 2 diabetes and cardiovascular disease [1], [4], [5]. More recently, we identified the concomitant presence of lymphoid cells, more specifically NK and NKT as well as γδ T cells in adipose tissues [10]. Although the presence of these subclasses of lymphoid cells as well as macrophages in adipose tissue is not still well understood, they represent the innate part of the immune system in vertebrate.
Among adipose tissues, there are several evidences demonstrating that visceral fat produces larger amounts of some adipokines and contains more inflammatory and immune ancestral cells than other fat depots [10], [11], [12]. This might be related to the association between increased visceral fat mass and adverse metabolic and cardiovascular consequences of obesity [13], [14], [15].
The relationship between adipose tissue and immune system is believed to be related to the secretion of numerous adipokines among them leptin of which the amount is correlated to fat mass [16], [17], [18], [19]. The leptin receptor is largely expressed in hematopoietic and immune cells [20], [21]. Leptin could support T lymphocyte development in thymus, T cell homeostasis, function and pro-inflammatory immune responses [17], [19], [21], [22], [23], [24], [25]. Furthermore, Th1-promoting effects of leptin have been linked to enhanced susceptibility to experimental autoimmune diseases [26].
The aims of this work were to examine the relationship between lymphocyte number and phenotype and the weight of internal and subcutaneous fat pads and to investigate a putative leptin involvement in these changes.
Section snippets
Animals
C57BL/6N and ob/ob male mice (Harlan, Gannat, France) were kept (n = 5 per cage) in a controlled environment (12 h light/dark cycle at 21°C) with free access to water and food. Food was provided by UAR (Villemoisson sur Orge, France). One group of control mice and the obese animals were fed a regular chow that consisted of 21% protein, 67% carbohydrate and 12% fat. A second group (n = 24) was fed with a high-fat (HF) diet (21% protein, 37% carbohydrate and 36% fat) from week 5 to 16. Control
Lymphocyte content varies with epididymal adipose tissue weight
First, we investigated the location of ancestral lymphoid cells and their changes occurring during adipose tissue enlargement in epididymal and inguinal pads from male mice with a great range of fat pad weight: 1) physiological range, i.e. mice at different ages from 7 to 28 weeks, 2) pathological conditions, i.e. mice fed with a high-fat diet up to 12 weeks. Immunohistological analyses on paraffin sections clearly revealed a tight relationship between CD3 (T cells) or CD49b (NK cells) positive
Acknowledgments
We thank Manolita Belliure for technical assistance and Yara Barreira and Jean marc Lerme of the animal quarter service for the care of the animals.
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