Abstract
Obesity induces local/systemic inflammation accompanied by increases in macrophage infiltration into adipose tissue and production of inflammatory cytokines, chemokines, and hormones. Previous studies have shown that probiotics could improve the intestinal dysbiosis induced by metabolic diseases such as obesity, diabetes, and metabolic syndrome. Microorganisms could (directly or indirectly) affect adipokine levels due to their capacity to induce translocation of several intestinal microbial antigens into systemic circulation, which could lead to metabolic endotoxemia or produce immunomodulation in different organs. The aim of the present study was to select non-inflammatory lactic acid bacteria (LAB) strains with the capacity to modulate adipokine secretion by the adipose tissue. We wish to elucidate the role of potential probiotic strains in the regulation of the cross talking between immune cells such as macrophages and adipose cells. Mouse macrophage cell line RAW 264.7 was used for evaluating the ability of 14 LAB strains to induce cytokine production. The LAB strains were chosen based on their previously studied beneficial properties in health. Then, in murine adipocyte culture and macrophage–adipocyte coculture, we determined the ability of these strains to induce cytokines and leptin secretion. Tumor necrosis factor alpha, interleukin 6 (IL-6), IL-10, monocyte chemoattractant protein-1, and leptin levels were measured in cell supernatants. We also performed the detection and quantification of leptin receptor (Ob-Rb) expression in macrophage cell lines stimulated by these LAB strains. Differential secretion profile of cytokines in macrophage cells induced by LAB strains was observed. Also, the levels of Ob-Rb expression diverged among different LAB strains. In LAB-stimulated coculture cells (adipocytes and macrophages), we observed differential production of leptin and cytokines. Furthermore, we detected lower production levels in single culture than cocultured cells. The principal component analysis showed an association between the four clusters of strains established according to their inflammatory profiles and leptin adipocyte production and leptin receptor expression in macrophages. We conclude that coculture is the most appropriate system for selecting strains with the ability to modulate adipokine secretion. The use of microorganisms with low and medium inflammatory properties and ability to modulate leptin levels could be a strategy for the treatment of some metabolic diseases associated with dysregulation of immune response.
Highlights
Since the discovery of leptin, 21 years ago [1], the adipose tissue was the focus of several functional studies, in such a way that nowadays it could be considered as a potent endocrine and immune organ [2,3,4,5]
We demonstrated that oral administration of potential probiotic bacteria to a high-fat diet-induced obesity mice model ameliorates the alterations of leptin and cytokine levels along with partial restoration of the obesity-induced dysbiosis [21, 22]
This study supports the hypothesis that lactic acid bacteria (LAB) have capacity to induce adipokine secretion in strain-dependent manner, and this ability is related to their immune properties
Summary
Since the discovery of leptin, 21 years ago [1], the adipose tissue was the focus of several functional studies, in such a way that nowadays it could be considered as a potent endocrine and immune organ [2,3,4,5]. This feature is due to the peculiarity of the different cells that form this tissue: adipocytes, preadipocytes, endothelial cells, fibroblasts, and numerous immune cells including macrophages, B cells, T cells, and neutrophils mainly. Syndromes of malnutrition associated with excess/lack or dysfunction of adipose tissue certainly belong to these kinds of diseases [10]
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