Abstract
The hypothalamus is the main integrating center for metabolic control, regulating the response to nutrients and other metabolic signals to maintain energy homeostasis. This response includes not only neuronal circuits that control appetite, but also glial cells that are involved in nutrient processing and inflammatory responses to high fat intake. However, it is now clear that the metabolic response is different depending on the type of fatty acid consumed, but the mechanisms remain largely unknown. Our aim was to analyze the hypothalamic response to the consumption of a diet enriched with sunflower oil (SOD), high in oleic acid content, or palm seed oil (POD), with a high lauric acid content. Adult male C57BL/6N mice were given ad libitum access to a standard rodent chow diet enriched with SOD or POD, or to a standard rodent chow (SD) for 8 weeks. Energy intake and body weight were monitored weekly. Relative protein expression was analyzed by Western blotting and relative gene expression by RT-PCR. Levels of circulating hormones and cytokines were measured by multiplexing. Both the SOD and POD increased body weight and energy intake compared to SD (p<0.01). In contrast, only the SOD increased circulating insulin and leptin levels, but with both diets decreasing serum inflammatory cytokine levels. In the hypothalamus, neuropeptide Y (NPY) mRNA levels were lower in mice consuming the SOD compared to SD (p<0.01) with an increase in the relative levels in pro-opiomelanocortin (POMC) in response to both diets (p<0.05). No dietary effects were found on the mRNA levels of Agouti-related peptide (AgRP), the leptin receptor, the cytokines interleukin-6 or tumor necrosis factor α or the cell stress marker DNA damage-inducible transcript 3. There was no change in the relative protein levels of ionized calcium-binding adaptor molecule 1, a marker of microglia, or of glial fibrillary acidic protein, a marker of astrocytes. No activation of c-Jun N-terminal kinases (JNK) was found. To explore hypothalamic fatty acid metabolism, the expression of fatty acid synthase and carnitine palmitoyltransferase were analyzed, but with no significant effect detected. In conclusion, although both diets enriched in fat induce weight gain the metabolic response to these diets differs. Serum levels of insulin and leptin were higher and hypothalamic mRNA levels of the orexigenic neuropeptide NPY were lower on the SOD, which may suggest that this diet is more effective in activating the homeostatic mechanisms to reduce food intake, at least at this time-point, or leptin and insulin resistance onset. Further studies are necessary to determine the long-term secondary complications in response to these specific high fat diets. However, it is clear that the specific fatty acid composition of high-fat diets is of utmost importance.
