Modulation of adipocyte differentiation by omega‐3 polyunsaturated fatty acids involves the ubiquitin‐proteasome system

Abstract

We have evaluated the effects of three different omega-3 polyunsaturated fatty acids (ω-3 PUFAs) – docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) on fat accumulation and expression of adipogenic and inflammatory markers using both 3T3-L1 pre-adipocytes and differentiated 3T3-L1 adipocytes. Our results indicate that ω-3 PUFAs induce the degradation of fatty acid synthase through the ubiquitin-proteasome system, which is likely to have beneficial metabolic effect on adipose cells. Omega-3 PUFAs also increase overall levels of polyubiquitinated proteins, at least in part through decreasing the expression of proteasome subunits. Moreover, adipocytes are resistant to proteasome inhibition, which induces adipophilin while decreasing perilipin expression. On the other hand, ω-3 PUFAs decrease expression of SREBP1 while inducing expression of adipophilin and GLUT4. Moreover, all three ω-3 PUFAs appear to induce tumour necrosis factor-α without affecting NFκB levels. All three ω-3 PUFAs appear to have overall similar effects. Further research is needed to elucidate their mechanism of action.

n‐3 polyunsaturated fatty acids provoke a specific transcriptional profile in rabbit adipose‐derived stem cells in vitro

“…Besides, Perilipin A is assumed as one of the most abundant lipid droplet (LD)‐associated proteins (Brasaemle, Subramanian, Garcia, Marcinkiewicz, & Rothenberg, ). In the current study, it was the most up‐regulated gene by both n‐3 PUFAs and those findings differ from the results reported in the 3T3 model (Wójcik et al, ). We assume that the established changes in Perilipin mRNA could be due to species‐specific response (mice vs. rabbits) to PUFAs exposure.…”

Combinations of bio-active dietary constituents affect human white adipocyte function in-vitro

“…However, for the single compounds conflicting effects on these markers were reported previously. Supporting our results, a reduction of GLUT-4 mRNA and unaffected levels of FAS mRNA were shown in 3T3-L1 cells after Res (20 μM) [47] and EPA (100 μM) [48] treatment, respectively. Whereas, opposing to our human data, GLUT-4 and LPL mRNA expression was up-regulated after treating murine adipocytes with Lyc (2 μM) [19] and EPA (100 μM) [21], respectively.…”

Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial

“…However, based on our results, PNPLA3 I148M is involved in DHA/EPA mobilization in liver and subjects with PNPLA3 (I148M) GG genotype have lower levels of DHA (38). Additionally, omega-3 fatty acids decrease the expression of sterol response element binding protein 1c (SREBP1c), a key regulatory factor in hepatic lipogenesis (39), and recently it has been shown that carriers of the PNPLA3 148M allele have decreased de novo lipogenesis (22). Thus, it is possible that the lack of response to DHA+EPA treatment in decreasing liver fat % in subjects with PNPLA3 I148 MM could be due to the fact that these subjects already have low levels of de novo lipogenesis.…”