IL10/AMPK pathway was associated with the hippocampal anti-inflammatory response to high-sugar and high-fat diet...

The present experimental study aimed to evaluate the effect of consuming an obesogenic diet (OD) on serum and hippocampal inflammation and proteins related to energy metabolism, alongside, we evaluated how the same parameters responded to an OD withdrawal.

Thirty male 60-days-old Wistar rats were used.

The control group (n = 10) was fed the control diet across the whole experiment. The remaining animals were fed a high-sugar/high-fat (HSHF) diet for 30 days (n = 20) and half of them were placed on the control diet for 48 h (n = 10) afterwards.

OD intake decreased hippocampal AMPK phosphorylation, although, it did not increase serum inflammation and only increased hippocampal pNFκBp65 levels without any increase in the cytokines assessed. Moreover, OD withdrawal led to higher inflammatory markers in the serum and hippocampus and higher hippocampal AMPK phosphorylation. The mediation models applied suggested that the effect of OD withdrawal on hippocampal inflammation was driven by serum inflammation, which activated the hippocampal IL10/AMPK anti-inflammatory pathway as a response.

Our analyses suggest that OD withdrawal increases serum inflammation with hippocampal consequent inflammatory alterations. Despite the general assumption that improving diet improves health, this may not be immediate.