Elsevier

Experimental Cell Research

Volume 312, Issue 12, 15 July 2006, Pages 2195-2202
Experimental Cell Research

Research Article
Weight-dependent changes of immune system in adipose tissue: Importance of leptin

https://doi.org/10.1016/j.yexcr.2006.03.023Get rights and content

Abstract

Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly altered in obesity. Leptin, production of which is correlated to fat mass, is strongly involved in the relationships between adipose tissues and immune system. We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2) leptin was involved in such relationships. Immunohistological analyses revealed a tight relationship between the T and NK lymphocytes of the stromal vascular fraction and adipocytes. We identified a significant negative and positive correlation between EPI weight and the percentage of NK and total T cells respectively by cytofluorometric analyses. The NK and ancestral γδ T cell contents were directly dependent of leptin since they increased significantly in high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to control. By contrast, the αβ T cell content seemed independent of leptin because their percentages increased significantly with the EPI weight whatever the type of mice (control, HF, ob/ob). The present study suggests that adipose tissues present, according to their localization, different immunological mechanisms that might be involved in the regulation of adipose cells functions and proliferations.

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.

References (34)

  • S. Samartin et al.

    Obesity, overnutrition and the immune system

    Nutr. Res.

    (2001)
  • O. Lamas et al.

    Energy restriction restores the impaired immune response in overweight (cafeteria) rats

    J. Nutr. Biochem.

    (2004)
  • Z. Tian et al.

    Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation

    Biochem. Biophys. Res. Commun.

    (2002)
  • E. Elinav et al.

    Suppression of hepatocellular carcinoma growth in mice via leptin is associated with inhibition of tumor cell growth and natural killer cell activation

    J. Hepatol.

    (2006)
  • H. Ghanim et al.

    Circulating mononuclear cells in the obese are in a proinflammatory state

    Circulation

    (2004)
  • K. Clement et al.

    Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects

    FASEB J.

    (2004)
  • Y.H. Lee et al.

    The evolving role of inflammation in obesity and the metabolic syndrome

    Curr. Diabetes Rep.

    (2005)
  • Cited by (0)

    View full text