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Chapter 2.4.1
Module:  2.
Nutritional supplements bioactivity, functional properties and safety: in vitro & in vivo studies
Unit:  2.4.
Animal and cell culture models of Obesity, Metabolic Diseases and Intestinal Inflammation
Chapter:  2.4.1.
Cell culture models of obesity and metabolic diseases

Obesity and metabolic disease have arisen to be of paramount concern in public health all over the world. There is a strong link of the former with the adipose tissue, whose role as an endocrine organ, besides that of excess energy and nutrient storage, has gained much attention during the last years. Adipokines and proinflammatory cytokines are secreted by the adipose tissue and exert systemic metabolic and immunological effects. Low levels of chronic inflammation are considered hallmarks of plenty metabolic pathologies. A fundamental trait of obesity is the extravagant concentration of fat mass in white adipose tissue (WAT), which is achieved through the expansion of adipocyte volume (hypertrophy), increase in adipocyte number (hyperplasia) or both.

Adipocytes originate from mesenchymal stem cells (MSCs), which initially differentiate into lipoblasts, consequently into preadipocytes, and finally into mature adipocytes. Primary cell lines, such as mature adipocytes, MSCs, and preadipocytes can be easily isolated from adipose tissue homogenates. Additionally, numerous relative cell culture models have been established, including human, but mostly rodent, for the in vitro research of the adipogenic differentiation processes linked to obesity, as well as the potential antiobesity effects of dietary and drug compounds. A necessary step of such models is the use of differentiation cocktails to induce adipogenesis. Therefore, the bioactivity of nutritional or drug compounds can be tested by assessing their impact on the adipogenesis process itself, as well as adipocyte metabolism (i.e. lipogenesis, lipolysis, oxidation of fatty acids, browning), gene expression profile, and cell survival (more 2.4.1.). For example, the 3T3-L1, a well-characterized and reliable cell model for studying the conversion of preadipocytes into adipocytes developed from murine Swiss 3T3 cells, when treated with curcumin (5-20 µM) for 24 h, resulted in suppressed preadipocyte differentiation, increased adipocyte apoptosis, as well as elevated fatty acid oxidation and reduced fat accumulation.

Adipocytes may also be examined in co- or 3D- cultures with other cell types, such as macrophages, endothelial, or muscle cells, in order to research the relationship of fat with other tissues. Most often, macrophages, which are physiologically found in adipose tissue, are co-cultured with adipocytes, due to the high interest and need of examining interactions among obesity or insulin resistance and inflammation. The aforementioned example of 3T3-L1 cell line has been excessively exploited in such experimental setups. For instance, it has been exhibited that, when differentiated medium from 3T3-L1 cells was used to culture macrophages, the macrophage inflammatory response was inhibited if 3T3-L1 cells had been treated with phloretin and phlorizin (natural substances for diabetes combating).