Zinc Supplementation Decreases Obesity‐Related Neuroinflammation and Improves Metabolic Function and Memory in Rats

Abstract

Objective: The purpose of this study was to evaluate the effects of zinc (Zn) supplementation on metabolic and neuroinflammatory parameters in cafeteria diet (CAF)-induced obesity in Wistar rats. Methods: Animals were divided into four groups: control diet (CT); CT+Zn; CAF; CAF+Zn. The diet was administered for 20 weeks; Zn treatment (10 mg/kg/d) started at week 16 and it was conducted until the end of the diet protocol. Weight gain, visceral fat, and plasma levels of glucose, triglycerides, insulin, TNF-α, and IL-6, as well as homeostatic model assessment of insulin resistance, were assessed. Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) expression in the cerebral cortex and toll-like receptor 4 (TLR-4) in the cerebral cortex and hippocampus were evaluated. Memory was assessed by the novel object recognition test. Results: CAF diet increased weight gain, visceral fat, and plasma glucose, triglyceride, and TNF-α levels. Zn reversed the hyperglycemia caused by CAF diet and reduced IL-6 levels. In the cerebral cortex, GFAP was similar between groups; Iba-1 was increased by CAF diet but reduced in the CAF+Zn group. Zn reduced CAF-dependent TLR-4 increase in the hippocampus but not in the cerebral cortex. CAF-fed animals showed impaired recognition memory, whereas Zn reversed it. Conclusions: These findings demonstrate that Zn partially reverted obesity-related metabolic dysfunction and reduced neuroinflammation and memory deficit caused by CAF diet.

Zinc Supplementation Partially Decreases the Harmful Effects of a Cafeteria Diet in Rats but Does Not Prevent Intestinal Dysbiosis

“…This model elicits obesity-related disorders, such as dysbiosis, leaky gut, metabolic disorders, low-grade systemic inflammation, neuroinflammation, and behavioral dysfunction in rodents [ 42 , 44 ]. As expected, the chronic consumption of the CAF for 20 weeks increased body weight, as shown in a previous study [ 10 ]. Thus, the present work also aimed to evaluate Zn’s ability to reverse the mentioned harmful effects of obesity, since its supplementation started after obesity had already been developed.…”

“…Leftovers were evaluated, and food consumption was calculated at the end of the experiment. The average energy consumption of CT groups was 771.5 Kcal/day, while CAF groups consumed 963 Kcal/day [ 10 ].…”

“…Previous studies have shown that Zn supplementation may improve anthropometric measurements and reduce inflammatory markers, insulin resistance, oxidative stress, and obesity-related neuroinflammation. Thus, Zn supplementation reduces metabolic dysfunction and may decrease neurological impairment related to obesity [ 10 , 11 , 12 ].…”

Obesity and critical care nutrition: current practice gaps and directions for future research

“…The excessive visceral fat tissue and adipocyte hypertrophy seen in patients with obesity contributes to a pro-inflammatory environment, including higher levels of hormones like leptin that disrupt T cell function, which results in a suppressed immune response to infection [80]. Immune function may be influenced by nutritional factors such as vitamin D and arginine status, both of which have been reported to be reduced in non-ICU patients with obesity [81][82][83][84]. Beyond arginine and vitamin D, inflammation may be modulated by other dietary factors such as omega-3 fatty acids and fiber; therefore, the use of these immune-modulating nutrients (also known as immunonutrition) has been considered in critically ill patients with obesity who are hemodynamically stable.…”

The Obese Brain: Mechanisms of Systemic and Local Inflammation, and Interventions to Reverse the Cognitive Deficit

“…For example, high-sugar diets, which promote cognitive decline in young animals, are associated with high IL6 and IL1β levels in the dorsal hippocampus ( Hsu et al, 2015 ). The cafeteria diet model increased Iba-1 expression in the obese brain ( de Oliveira et al, 2021 ). Chronic HFD feeding for 12 weeks enhanced TNFα, IL6, and leptin levels in the hippocampus and also promoted microglial activation in the prefrontal cortex and hippocampus ( Gomes et al, 2020 ).…”