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Rapid Metabolic and Behavioral Maladaptations Following Short-Term Obesogenic Diet Withdrawal During Postweaning
Breno Picin Casagrande1, Vitória Rios Beserra1, Alessandra Mussi Ribeiro1
1Biosciences Department, Institute of Health and Society, Federal University of São Paulo, Santos, São Paulo, Brazil.
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.
Objectives:
This study investigated the short-term effects of OD withdrawal on metabolic, inflammatory, and anxiety-like behaviors in young male Wistar rats.
Methods:
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 h. 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 behavioral phenotype.
Results:
OD intake significantly increased caloric intake, visceral adiposity, hepatic glycogen, and triacylglycerol (TAG) levels. The 48-h withdrawal reduced TAG, induced hyperinsulinemia and hypoglycemia, and heightened inflammation in mesenteric fat, serum, and the hippocampus. Oxidative stress markers (superoxide dismutase [SOD] and malondialdehyde [MDA]) increased in the hippocampus, correlating with elevated serum corticosterone and heightened anxiety-like behavior in the Wt group compared to the other groups.
Conclusion:
Short-term withdrawal after only 2 weeks of OD intake exacerbates systemic and neuroinflammation, hippocampal oxidative stress, and anxiety-like behaviors, 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.

