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| Author(s): |
Camila Oliveira de Souza
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2017-12-04 |
| Examining board members: |
José Cesar Rosa Neto;
Niels Olsen Saraiva Câmara;
Marcelo Alves da Silva Mori;
Alice Cristina Rodrigues;
Ronaldo Vagner Thomatieli dos Santos
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| Advisor: | José Cesar Rosa Neto |
| Abstract | |
Palmitoleic acid (POA) is described as a lipokine, capable of improving insulin responsiveness, stimulating lipid oxidation and reducing inflammation, essential for the control of non-alcoholic fatty liver disease (NAFLD). Thus, we investigated whether POA can protect against the deleterious effects of a diet rich in saturated fat (HF-L) or trans fat (HF-T), verifying the role of PPARα and PPARγ. We used wild-type mice fed a standard diet (SD), or whole-body PPARα knockout (PPARαKO) mice or mice with myeloid cells selective-delected PPARγ (PPARγKOLyzCre+) fed a HF. The diets were administered for 12 weeks, and from the 10th week the animals were supplemented with oleic acid or POA (300mg/kg). Intraperitoneal macrophages extracted from WT, PPARαKO and PPARγKOLyzCre+ mice fed SD and stimulated with LPS or LPS+POA (600μM), were also analyzed. HF promoted insulin resistance, steatosis and exacerbated inflammation in the liver of mice, regardless of genotype. Although it did not reduce the lipids ectopic accumulation in the liver, or modulated the lipogenic factors expression, POA improved the peripheral and hepatic insulin response. In the liver, POA did not modulate factors of the insulin cascade, or adiponectin production, however, stimulated AMPK activation and increased FGF-21 levels, in a PPARα-dependent manner. POA reduced liver inflammation by decreasing TLR4, NFκB and inflammatory factors, but mainly by inhibiting the macrophage polarization of the liver to the M1 phenotype, an effect that occurred even in PPARγKOLyzCre+ mice, despite the increased gene and protein expression of PPARγ observed in macrophages with POA, in vivo and in vitro. Our data indicate that the POA promotes beneficial effects against glucose intolerance and hepatic and peripheral insulin resistance induced by a high fat diet through the activation of AMPK, FGF21 and PPARα. And, by reducing the M1 polarization of macrophages, independent of PPARs, this 16: 1n-7 fatty acid is able to reduce inflammation in the liver induced by high fat diet. (AU) | |
| FAPESP's process: | 13/04765-1 - Palmitoleic acid supplementation effects on immune-metabolics alterations induced by high fat diet on PPAR knockout mice |
| Grantee: | Camila Oliveira de Souza |
| Support Opportunities: | Scholarships in Brazil - Doctorate |