Public Thesis Defense - ELI

Dietary fatty acids and methylmercury impact adipogenesisand lipid metabolism in rainbow trout by Gilles TINANT

Pour l'obtention du grade académique de doctorat en Sciences agronomiques et Ingénierie biologique

Adipose tissue is an important organ in fish, playing an essential role in lipid storage and energy homeostasis. This organ is also known to be a target for various environmental pollutants. Fish ingest in their diet both lipids, which are mainly made up of fatty acids whose profile can vary according to diet, and methylmercury (MeHg), which is an ubiquitous environmental contaminant in aquatic ecosystems. To date, however, little is known about the effects of MeHg and certain n-3 and n-6 polyunsaturated fatty acids (PUFA) on the development and metabolism of adipose tissue as well as on lipid homeostasis in fish. The present work aims at investigating these impacts in rainbow trout (Oncorhynchus mykiss), using both in vivo and in vitro approaches.

Four dietary fatty acids were studied in vivo, with or without MeHg: eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) that are n-3 long-chain PUFA largely present in fish oil, and linoleic acid (LA, 18:2 n-6) and α-linolenic acid (ALA, 18:3 n-3) that are PUFA typical of plant-derived oils, all found in fish feed formulated for aquaculture. The diet enriched in LA increased the whole-body lipid content of the juvenile rainbow trout compared to diets rich in n-3 PUFA, while MeHg had a negative effect on body lipid levels, regardless of the diet. Nevertheless, both LA and MeHg exacerbated the hypertrophy of perivisceral adipocytes.

The effects of fatty acids and mercury were also studied in vitro in order to decipher the molecular mechanisms involved. MeHg exerted pro-adipogenic effects on preadipocytes, with upregulated expression of several genes specific to adipocyte development and lipid deposition like fatty acid synthase, apolipoprotein Eb, perilipin 2 and glucose-6-phosphate dehydrogenase. Moreover, MeHg induced a dose-dependent intracellular lipid accumulation that persisted even after the MeHg exposure ceased and mercury was released by the cells. On the other hand, seven fatty acids were studied in in vitro preadipocytes, namely ALA, EPA, DHA, LA, oleic acid (OA, 18:1 n-9), all of which highly represented in the fish diets, as well as arachidonic acid (AA, 20:4 n-6) and docosapentaenoic acid (DPA, 22:5 n-6), both primarily derived from the n-6 bioconversion pathway. While each of them affected the in vitro adipogenesis, DPA and DHA appeared to be the most lipogenic fatty acids. DPA acted by increasing the expression of the transcription factor C/EBPd while DHA upregulated the expression of genes involved in neutral lipid synthesis, notably lipoprotein lipase, fatty acid transport protein 1 and glycerol-3-phosphate dehydrogenase.

Overall, this work gets new insights into the pivotal effects of dietary fatty acids and exposure to MeHg on adipocyte development using complementary in vivo and in vitro approaches. Interestingly, MeHg negatively affected whole-body lipid storage while displaying pro-adipogenic effects in preadipocytes, providing further evidence on the role of environmental pollutants in adipose tissue dysfunction. On the other hand, fatty acids exhibited various lipogenic effects depending on their nature and through distinct pathways. These results are of interest for aquaculture and basic research to promote fish and human health and open the door to future research on adipose tissue in the fields of nutrition and ecotoxicology.

Jury members :

• Pr Cathy Debier (UCLouvain) (Supervisor)
• Pr Isabelle Donnay (UCLouvain) (Chairperson)
• Pr Patrick Kestemont (UNamur)
• Pr Yvan Larondelle (UCLouvain)
• Pr Cinta Porte (CSIC, Espagne)
• Pr Jean-François Rees (UCLouvain)

Pay attention : the public defense of Gilles TINANT ill also take place in the form of a videoconference

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