Rapid metabolic and behavioural maladaptations following short-term obesogenic diet withdrawal during post-weaning development in male Wistar rats

Background Obesogenic diets (ODs) are known to trigger metabolic and inflammatory disturbances. However, the effects of short-term OD withdrawal on systemic and neuroinflammatory parameters remain unclear.

This study investigated the short-term effects of OD withdrawal on metabolic, inflammatory, and anxiety-like behaviours in young male Wistar rats.

Three-week-old male Wistar rats were fed either a control (Ct, n=5) or high-sugar/high-fat (HSHF) diet for 14 days. Animals in the HSHF group were further divided into no-withdrawal (NWt, n=5) and withdrawal (Wt, n=5) groups, where Wt received a control diet for 48 hours. Food intake, body mass, adiposity, serum metabolic parameters, hepatic energy stores, inflammatory markers (serum, liver, hypothalamus, hippocampus, mesenteric fat), and oxidative stress markers in the hippocampus were measured. Elevated plus maze and open field were used to characterize behavioural phenotype.

OD intake significantly increased caloric intake, visceral adiposity, hepatic glycogen, and TAG levels. The 48-hour withdrawal reduced TAG, induced hyperinsulinemia and hypoglycaemia, and heightened inflammation in mesenteric fat, serum, and the hippocampus. Oxidative stress markers (SOD and MDA) increased in the hippocampus, correlating with elevated serum corticosterone and heightened anxiety-like behaviour in the Wt group compared to the other groups.

Short-term withdrawal after only two weeks of OD intake exacerbates systemic and neuroinflammation, hippocampal oxidative stress, and anxiety-like behaviours, indicating rapid negative responses to dietary transition. These findings identify short-term dietary withdrawal during early development as a distinct and biologically active phase, rather than an immediate recovery period. Competing Interest Statement The authors have declared no competing interest. Footnotes Email addresses: breno.casagrande{at}unifesp.br, rios.vitoria{at}unifesp.br, alessandra.ribeiro{at}unifesp.br, pisani{at}unifesp.br Revisions were carried out as part of the peer review process of Brain and Behavior (ISSN 2162-3279). The manuscript has now been approved and will be available at DOI:10.1002/brb3.71492