Poster Presentation Joint Annual Scientific Meeting of the Nutrition Society of NZ and the Nutrition Society of Australia

High-fat diet promotes inflammation via two separate mechanisms in hypothalamic neurons and microglia (#P41)

D Sergi 1 , A C Morris 1 , M G Martinoli 2 , Lynda Williams 1
  1. Rowett Institute of Nutrition and Health, Aberdeen, United Kingdom
  2. Research Group in Neuroscience, Universite du Qubec, Quebec, Canada

Background/Aims: Recent evidence has implicated dietary long chain saturated fatty acid (SFA) induced inflammation, and subsequent leptin and insulin insensitivity, in the hypothalamus as key in the development of obesity. SFAs are thought to mediate hypothalamic inflammation by activating the Toll-like receptor 4 (TLR4), but this remains controversial. Our aim was to clarify the role of TLR4 in diet-induced hypothalamic inflammation.

Methods: We used semi-quantitative Real-Time PCR to test the ability of 200 µM palmitic acid (PA) and 100 nM lipopolysaccharide (LPS), a known stimulator of TLR4, to induce inflammation in cultured hypothalamic neurons, mHypoE-N42 (N42), and microglia (N9). Differences between groups were tested using Student’s t-tests.

Results LPS increased IL-6, TNFα (P<0.001) and IL-1β (P<0.01) gene expression in microglia but not in N42 neurons despite neuronal expression of TLR4. Adding the TLR4 inhibitor (CLI-095, 1 µM) alongside LPS completely abrogated the inflammatory response in microglia (P<0.001). To test whether PA induced inflammation was dependent on TLR4 activation we challenged N42 neurons and N9 microglia with PA in the presence and absence of CLI-095. PA elicited an inflammatory response compared to controls in both cell lines (P<0.001). However, CLI-095 inhibited the PA induced inflammatory response in microglia (P<0.001) but not in neurons.

Conclusions: This study demonstrates that TLR4 signalling is required for PA induced inflammation in microglia but not in neurons.

Funding source(s): Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS) and a Scottish Universities Life Sciences Alliance (SULSA MSD) studentship.