Zinc (Zn) plays an important role in metabolic homeostasis and may modulate neurological impairment related to obesity. The present study aimed to evaluate the effect of Zn supplementation on the intestinal microbiota, fatty acid profile, and neurofunctional parameters in obese male Wistar rats. Rats were fed a cafeteria diet (CAF), composed of ultra-processed and highly caloric and palatable foods, for 20 weeks to induce obesity. From week 16, Zn supplementation was started (10 mg/kg/day). At the end of the experiment, we evaluated the colon morphology, composition of gut microbiota, intestinal fatty acids, integrity of the intestinal barrier and blood–brain barrier (BBB), and neuroplasticity markers in the cerebral cortex and hippocampus. Obese rats showed dysbiosis, morphological changes, short-chain fatty acid (SCFA) reduction, and increased saturated fatty acids in the colon. BBB may also be compromised in CAF-fed animals, as claudin-5 expression is reduced in the cerebral cortex. In addition, synaptophysin was decreased in the hippocampus, which may affect synaptic function. Our findings showed that Zn could not protect obese animals from intestinal dysbiosis. However, an increase in acetate levels was observed, which suggests a partial beneficial effect of Zn. Thus, Zn supplementation may not be sufficient to protect from obesity-related dysfunctions.

Obesity has been linked to cognitive decline and adverse effects on brain health. Zinc (Zn) is a mineral with important metabolic functions that can modulate obesity-related neurological impairment. Thus, the present study aimed to evaluate the effects of 12 weeks of Zn supplementation on the inflammatory profile, cognitive function, and mood of overweight or obese women through a double-blind, placebo-controlled study. The study included 42 women aged between 40 and 60, randomly divided into two groups: Zn supplementation (30 mg/day) or placebo for 12 weeks. Data regarding sociodemographic, anthropometric, dietary, and physical activity were collected. Mini-mental state examination (MMSE), verbal fluency test, clock drawing test, and Stroop test were performed. Anxiety and depression symptoms were assessed using the Beck anxiety inventory and the BDI-II, respectively. Saliva samples were collected to evaluate IL-1β, IL-6, TNF-α, insulin, nitrite, and Zn levels. Of the 42 participants (mean age 49.58 ± 6.46 years), 32 were included in the study analyses. Changes in body weight and macronutrient consumption were not different between placebo and Zn supplementation groups. Cognitive scores on the MMSE and Stroop tests were higher in the Zn supplementation group than in the placebo group. Salivary levels of IL-1b and Zn increased in the Zn group compared to placebo. There was no significant change in the adjusted means of the BDI-II and BECK scores between the zinc vs. placebo groups. Twelve weeks of Zn supplementation was able to partially improve the cognitive scores assessed in overweight or obese women, regardless of weight loss. These findings suggest that Zn supplementation can be considered an adjunct strategy to enhance cognitive health in overweight or obese women.