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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 (?-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 ?-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, ?-3 PUFAs decrease expression of SREBP1 while inducing expression of adipophilin and GLUT4. Moreover, all three ?-3 PUFAs appear to induce tumour necrosis factor-? without affecting NF?B levels. All three ?-3 PUFAs appear to have overall similar effects. Further research is needed to elucidate their mechanism of action.

SUBMITTER: Wojcik C

PROVIDER: S-EPMC4000111 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Wójcik Cezary C Lohe Kimberly K Kuang Chenzhong C Xiao Yan Y Jouni Zeida Z Poels Eduard E

Journal of cellular and molecular medicine 20140401 4

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 ...[more]

PMID: 24834523

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Project description:Cerebral microinfarcts have significant effects on the development of geriatric neurological disorders, including vascular dementia and Alzheimer's disease. However, little is known about the pathophysiological mechanisms involved in the evolution of microinfarcts and potential treatment and prevention against these microvascular ischemic lesions. In the present study, the "single cortical microinfarct model" generated via occluding a penetrating arteriole by femtosecond laser ablation and the "multiple diffuse microinfarcts model" induced by unilateral injection of cholesterol crystals through the internal carotid artery were established to investigate the pathophysiological mechanisms underlying the evolution of microinfarcts and the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on alleviating microinfarct burdens and functional deficits. The occlusion of a single penetrating arteriole led to a distinct cortical microinfarct, which manifested as neuronal loss and occupation of activated glial cells in the ischemic core. Using Fat-1 transgenic mice and fish oil supplements, we demonstrated that both endogenously-generated and exogenously-delivered ω-3 PUFAs significantly inhibited the activation of receptor-interacting serine/threonine protein kinases 1 (RIPK1) and its downstream apoptosis-associated proteins, mitigated cell apoptosis, and anatomically reduced the microinfarct size. The protective effects of ω-3 PUFAs against microinfarcts were further verified in a multiple diffuse microinfarcts model, where ω-3 PUFAs significantly attenuated cell apoptosis as revealed by TUNEL staining, alleviated the diffuse microinfarct burdens and remarkably improved the functional deficits as evidenced by reduced spontaneous anxiety, increased preference for the novel object, and improved hippocampal-based learning and short-term memory. Together, these findings demonstrate that enriched brain ω-3 PUFAs are effective for reducing microinfarct burdens and improving the function deficits, which support the clinical research and application of ω-3 PUFAs in the treatment or prophylaxis in vascular dementia.

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

Publications

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

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