Effects of Taurine Supplementation Upon Food Intake and Central Insulin Signaling in Malnourished Mice Fed on a High-Fat Diet - Advances in Experimental Medicine and Biology - page 97

observations above since TAU supplementation also decreased food intake and
increased hypothalamic pAkt in control mice fed on an HFD.
Few studies reported CNS insulin action in malnutrition. Mollinedo et al. ( 2010 )
described no significant difference in the IRS-1/2 and Akt protein content in the cere-
bral cortex of rats submitted to caloric restriction. On the other hand, microarray anal-
ysis in the hypothalamus of rats born to protein-restricted dams revealed increased
expression of several genes involved in insulin signaling such as IRS-1, PI3K, and Akt
(Orozco-Solís et al. 2010 ). However, in our study we observed lower pIRS-1 without
modification on pAkt hypothalamic content in protein-restricted mice (Fig. 10.4 ).
It is known that rats fed on an HFD presented high levels of tumor necrosis factor
(TNF)-a , interleukin-1 b, and interleukin-6 in the hypothalamus (De Souza et al.
2005 ) . Hypothalamic TNF- a impairs the anorexigenic action induced by insulin
and leptin, via serine phosphorylation of IRS-1, inactivating and inhibiting subse-
quent events of hypothalamic insulin signaling (Romanatto et al. 2007 ; Amaral
et al. 2006 ; De Souza et al. 2005 ). Moreover, other proteins such as SOCS3 and
PTP-1B are activated and promote degradation or dephosphorylation of the IRS
(Pirola et al. 2004 ; Zabolotny et al. 2008 ; Bence et al. 2006 ) . In accordance with
these studies, our model of obesity induced by HFD also showed a decreased hypo-
thalamic content of pIRS-1 indicating central insulin action impairment. TAU sup-
plementation enhanced pAkt and decreased food intake only in CHT mice (Figs. 10.3
and 10.4 ), showing that malnutrition leads to hypothalamic dysfunction that was not
prevented by TAU.

10.5 Conclusion

In conclusion our results show that mice fed an HFD developed obesity, hypercho-
lesterolemia, glucose intolerance, and calorie intake disturbances, both in control
and malnourished mice. TAU promoted increased hypothalamic insulin action
which prevented overfeeding and obesity. Protein-restriction promoted metabolic
disturbances that were not restored by TAU supplementation showing enhanced risk
to develop metabolic syndrome.

Acknowledgements This study was supported by grants from Fundação de Amparo à Pesquisa
do Estado de São Paulo (FAPESP), Conselho Nacional para o Desenvolvimento Científico e
Tecnológico (CNPq), and Instituto Nacional de Ciência e Tecnologia (INCT).

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