**6. References**

Alcudia F, Cert A, Espartero JL, Mateos R, & Trujillo M. (2004) Method of preparing hydroxytyrosol esters, esters thus obtained and use of same. PCT WO 2004/005237.

Moreover, the antioxidant activity of encapsulated HT, together with the photoprotection effect of β-CD on HT, has been evaluated by scavenging of the stable DPPH radical. It has been proven that β-Cyclodextrin acts as a secondary antioxidant and provides a moderate

β-Cyclodextrin exerts a strong photoprotection of HT upon UV irradiation, which could be deduced from the EC50 values (Table 2). For equimolecular mixtures of HT and -CD at 1.2 mM, the observed degradation after 24 h and 48 h is similar to the degradation found for HT at the same concentration and time (entries 4 and 5) showing no protection at 24 h and only a slight protection after 48 h. However, using 1:4 mixtures of HT (1.2 mM) and -CD (4.8 mM), a remarkable reduction of the degradation rate was observed when compared with pure HT. In this way, the complexation of HT with cyclodextrins might enhance stability, improve its

improvement of the radical scavenging activity of HT measured by the DPPH assay.

performance as antioxidant and extend its storage life (López-García et al., 2010).

Table 2. Effect of the encapsulation of HT on its photostability

**4. Conclusions** 

bioavailability.

**6. References** 

**5. Acknowledgement** 

Entry Antioxidant [HT] (mM) Irradiation time (h) EC50

1 HT 1.2 12 119.0 ± 1.4 2 HT 1.2 24 353.6 ± 23.4 3 HT 1.2 48 1436.1 ± 73.2 4 HT-βCD (1:1) 1.2 24 357.2 ± 30.7 5 HT-βCD (1:1) 1.2 48 1011.6 ± 171.9 6 HT-βCD (1:4) 1.2 12 112.4 ± 6.4 7 HT-βCD (1:4) 1.2 24 198.0 ± 4.6 8 HT-βCD (1:4) 1.2 48 387.2 ± 13.3

Hydroxytyrosol is a phenolic compound that can be isolated from olive oil mill wastewaters. The remarkable biological properties of this compound, mainly due to its strong antioxidant activity, has stimulated the synthesis of a series of derivatives, some of them are also naturally-occurring in the olive tree. Among these derivatives hydroxytyrosyl esters and ethers are of great interest, as some of them show strong antioxidant activity and improved

We thank the Junta de Andalucía (P08-AGR-03751 and FQM 134) and Dirección General de Investigación of Spain (CTQ2008-02813) for financial support. M.A.L.G. and A.M. thanks

Alcudia F, Cert A, Espartero JL, Mateos R, & Trujillo M. (2004) Method of preparing

hydroxytyrosol esters, esters thus obtained and use of same. PCT WO 2004/005237.

Ministerio de Educación and Junta de Andalucía, respectively, for their fellowships.

(g HT / kg DPPH)


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**21** 

*France* 

**Differential Effect of Fatty Acids** 

**in Nervous Control of Energy Balance** 

Christophe Magnan, Hervé Le Stunff and Stéphanie Migrenne

*Université Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative, Equipe d'accueil conventionnée Centre National de la Recherche Scientifique, Paris,* 

Energy homeostasis is kept through a complex interplay of nutritional, neuronal and hormonal inputs that are integrated at the level of the central nervous system (CNS). A disruption of this regulation gives rise to life-threatening conditions that include obesity and type-2 diabetes, pathologies that are strongly linked epidemiologically and experimentally. The hypothalamus is a key integrator of nutrient-induced signals of hunger and satiety, crucial for processing information regarding energy stores and food availability. Much effort has been focused on the identification of hypothalamic pathways that control food intake but, until now, little attention has been given to a potential role for the hypothalamus in direct control of glucose homeostasis and nergy balance. Recent studies have cast a new light on the role of the CNS in regulating peripheral glucose via a hypothalamic fatty acid (FA)-sensing device that detects nutrient availability and relays, through the autonomic nervous system, a negative feedback signal on food intake, insulin sensitivity and insulin secretion. Indeed, accumulating evidences suggest that FA are used in specific areas of CNS not as nutrients, but as cellular messengers which inform "FA sensitive neurons" about the energy status of the whole body (Blouet & Schwartz, 2010; Migrenne et al., 2006; Migrenne et al., 2011). Thus it has been described that up to 70% of hypothalamic arcuate nucleus (ARC) and ventromedian nucleus (VMN) neurons are either excited or inhibited by long chain fatty acids such as oleic acid (Jo et al., 2009; Le Foll et al., 2009; Migrenne et al., 2011). Within the VMN, 90% of the glucosensing neurons also have their activity altered by FA. In a large percentage of these neurons, glucose and FA have opposing effects on neuronal activity, much as they do on intracellular metabolism in many other cells (Randle et al., 1994). Neuronal FA sensing mechanisms include activation of the KATP channel by long chain fatty acid acyl CoA (Gribble et al., 1998) or inactivation by generation of ATP or reactive oxygen species during mitochondrial β-oxidation (Jo et al., 2009; Le Foll et al., 2009; Migrenne et al., 2011; Wang et al., 2006). Many fatty acid sensing neurons are activated by interaction of long chain fatty acids with the fatty acid transporter/receptor, FAT/CD36, presumably by activation of store-operated calcium channels by a mechanism that is independent of fatty acid metabolism (Jo et al., 2009). Importantly, most neurons utilize FA primarily for membrane production rather than as a metabolic substrate (Rapoport et al., 2001; Smith & Nagura, 2001) and only nanomolar concentrations of fatty acid are required to

**1. Introduction** 

