The Furan Fatty Acid 9M5 Acts as a Partial Ligand to Peroxisome Proliferator‐Activated Receptor gamma and Enhances Adipogenesis in 3T3‐L1 Preadipocytes

Abstract

A food that has been praised for its beneficial effects on overall health is fish, particularly its polyunsaturated n-3 fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). However, it has recently been suggested that minor fatty acids such as furan fatty acids are needed in combination with DHA and EPA to exert these positive effects of fish and fish oils. Only recently have furan fatty acids become available in quantities that allow the investigation of their biofunctional properties. In this study, the uptake and effect of the furan fatty acid 9-(3-methyl-5-pentylfuran-2-yl)-nonanoic acid (9M5) as a sole component and in combination with DHA and EPA on adipogenesis were analyzed using the 3T3-L1 cell model. 9M5 is taken up and metabolized into 7M5, 5M5, and 3M5 in 3T3-L1 adipocytes during a 24-h period as shown with gas chromatography with mass spectrometry (GC/MS). Furthermore, 9M5 significantly increased lipid accumulation during the differentiation process of 3T3-L1 preadipocytes into adipocytes. In addition, the combinations of DHA + 9M5 and EPA + DHA + 9M5 also exerted a significant increase compared to control adipocytes. 3T3-L1 cells incubated with 9M5 resulted in an increased protein expression of PPARγ, C/EBPα, FABP4, and adiponectin, although not to the extent that DHA as a sole component or DHA + 9M5 did. Earlier studies have shown that DHA is a natural ligand for PPARγ, thus being a potential alternative to the antidiabetic thiazolidinediones. We show that 9M5 activates a PPARγ-responsive reporter gene and could therefore be a natural ligand for PPARγ.

Virtual screening of potentially endocrine-disrupting chemicals against nuclear receptors and its application to identify PPARγ-bound fatty acids

“…Among the fatty acids that exhibited higher affinity to PPARγ than endogenous ligands such as DHA and EPA, FNA (9M5) was reported to enhance adipogensis (Lauvai et al 2019), and to promote significantly more lipid accumulation than PUFAs like DHA and EPA even at lower concentrations, consistent with our results. However, it is currently unknown if FNA can directly interact with and activate PPARγ.…”

Potential favourable health effects of some dietary uncommon fatty acids

“…Several in vitro studies support this hypothesis (Graff et al, 1984;Okada et al, 1996;Fuchs and Spiteller, 1999) as well as studies conducted in humans (Wahl et al, 1994;Zheng et al, 2016;Tovar et al, 2017). Moreover, in vitro FuFAs modulate lipid metabolism in adipose tissues (Lengler et al, 2012;Lauvai et al, 2019). The 3-carboxy-4methyl-5-propyl-2-furanpropanoic acid (CMPF), a degradation product of FuFAs, also derived from the metabolism of n-3 PUFAs, could prevent or even reverse hepatic steatosis (Prentice et al, 2018;Dai et al, 2019;Mohan et al, 2019).…”

“…FuFAs possess antioxidant properties due to the presence of the furan ring (Okada et al, 1990(Okada et al, , 1996Masuchi Buscato et al, 2020). They also have anti-microbial (Knechtle et al, 2014;Dasagrandhi et al, 2016;Kimura et al, 2018) and anti-inflammatory (Wakimoto et al, 2011;Khan et al, 2018;Lauvai et al, 2019) properties. FuFAs may thus participate to the anti-inflammatory effects of fish oils and fish-based diets.…”

Metabolic Differences between Subcutaneous and Visceral Adipocytes Differentiated with an Excess of Saturated and Monounsaturated Fatty Acids

“…Indeed, oleic acid and other polyunsaturated fatty acids: Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) were shown to act as natural ligands for PPARG, stimulating the expression of PPARG, CEBPA , and adiponectin [ 15 , 23 ]. On the other hand, inhibition of PPARG attenuates lipid formation and adipogenesis [ 24 ]. These results may explain the beneficial effect of oleic acid on overall glucose and lipid metabolism through increasing the plasticity of adipose tissues and promoting lipid accumulation and storage, thus reducing lipid accumulation in other tissue or organs, as well as overall lipotoxicity [ 25 ].…”