Effects of Selected Bioactive Food Compounds on Human White Adipocyte Function

Christel Björk; Uta Wilhelm; Susanne Mandrup; Bjørk Ditlev Larsen; Alessandra Bordoni; Per Hedén; Mikael Rydén; Peter Arner; Jurga Laurencikiene


Nutr Metab. 2016;13(4) 

In This Article


It is well established that white adipose tissue (WAT) metabolism and inflammatory status affect whole body homeostasis.[1] The major role of WAT is to store and release energy. Storing energy in the form of triacylglycerol (TAG) in adipocytes through lipogenesis has been shown to regulate systemic insulin sensitivity.[2,3] Hydrolysis of TAGs into non-esterified fatty acids and glycerol is a tightly controlled enzymatic process denoted lipolysis. Basal (spontaneous) lipolytic activity is increased in obesity and may attenuate insulin sensitivity through increased delivery of FAs to skeletal muscle (reviewed in[4]). Another important aspect of WAT function is the secretion of a class of proteins called adipokines, several with pro- or anti-inflammatory properties (see[1] for review). An elevated release of monocyte chemoattractant protein-1 (MCP-1/CCL2) produced by adipocytes[5,6] recruits macrophages, which in turn promote a chronic low grade inflammation in WAT.[7] Release of other pro-inflammatory adipokines, such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNFα) and chemerin may also contribute to metabolic disorders such as insulin resistance, dyslipidemia, hypertension and cardiovascular disease,[8–10] which are associated with the development of the metabolic syndrome.[11] The anti-inflammatory adipokine adiponectin has on the other hand been shown to correlate negatively with BMI (Body mass index, defined as body weight in kilograms divided by height in meters squared) and positively with insulin sensitivity[12,13] and its high levels are associated with a lower risk for developing type 2 diabetes.[14]

Diet composition can affect the metabolic and endocrine function of WAT as well as overall energy balance.[15] Certain diets that provide high amounts of bioactive components may have beneficial clinical effects partly due to their anti-inflammatory effects on adipose tissue (see[15,16] for reviews). A number of natural bioactive compounds that can be added to the food or their metabolic derivatives have been tested for their action on fat cells. The omega-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) can be synthesized from the essential alpha-linoleic acid. However, minor (clinically insufficient) amounts are synthesized endogenously and significant levels can only be provided exogenously through intake of fish and fish oil. A previous study using human adipocytes and WAT suggested an anti-inflammatory effect of DHA via decreased levels of IL-6 and MCP-1.[17] In vitro studies regarding the regulation of DHA on adiponectin production have been performed both in mouse and human adipocytes, however the results are conflicting.[18–20] Anthocyanins (AC) are naturally occurring polyphenol compounds present in blue or purple berries, fruit and vegetables.[21] Cyanidin-3-glucoside (C3G) is the most studied anthocyanin that together with its main metabolite protocatechuic acid (PCA) has been shown to be protective against insulin resistance in both human adipocytes in vitro[22,23] and an in vivo diabetic mouse model[24,25] as well as having anti-inflammatory properties.[22,24–26] Beta-glucan (BG) is a soluble dietary fiber present in oats and barley. However, BG is not absorbed in vivo, but its metabolism by the gut microbiota results in increased production an uptake of short-chain fatty acids (SCFA), such as propionic acid (PI), which has been shown to regulate adipokine production and enhance lipogenesis and glucose uptake in isolated human WAT.[27,28]

Most studies investigating effects of these compounds have been conducted in murine adipose cell lines or in vivo mouse or rat models,[29–32] which display a number of species-specific differences concerning adipose tissue function.[33–35] Furthermore, in previous studies the compounds have been tested individually and the experimental conditions as well as fat cell model systems have varied markedly. In addition, in most cases a single metabolic or inflammatory aspect of adipocyte function has been investigated.

As a part of the pan-European study PATHWAY-27 (http://www.pathway27.eu/) with the overall aim to contribute to better understanding of the mechanisms of bioactive nutrients on metabolism in different food-environments and help to develop health-promoting food for the growing demand of the health-conscious consumer, we have investigated the role of selected bioactives or their main metabolites on adipocyte phenotypes linked to obesity and the metabolic syndrome.