Evaluation of action citral on lipopolysaccharide-induced fever in obese mice with high-fat diet

Abstract

Obesity is considered a public health problem, which has grown in several countries around the world. Ingestion of rich-fat diet leads to a progressive increase in adipose tissue and triggers changes in the modulation of the immune system, raising the levels of inflammatory mediators (TNF-±, IL-6 and leptin), which are considered systemic biomarkers. Low-grade chronic inflammation associated with obesity increases susceptibility to infections, result in alterations in host homeostasis capable of promoting effector responses to protect it from the pathogen infection. One of the main triggered responses is fever, defined as the controlled increase in body temperature (Tb) due to the production of peripheral inflammatory mediators such as IL-1², IL-6, TNF-± and PGE2 systemic and especially PGE2, produced in the preoptic area of the hypothalamus (AVPO). In order to minimize the harmful effects of fever, non-steroidal anti-inflammatory drugs (NSAIDs) are used as the current therapy, but indiscriminate and chronic-use can cause significant harm to users, such as the formation of gastric ulcers. In view of this, the present project seeks to study a therapeutic alternative with effective anti-inflammatory, antipyretic and non-aggressive action of the gastric mucosa for clinical application in an effective and safe way. Previous work has shown that citral, a racemic mixture of monoterpenes, exhibits antipyretic and anti-inflammatory action in animals fed a standard diet. Thus, it is plausible to characterize the citral response profile in mice fed standard and high-fat diet (HFD) against low dose lipopoilysaccharide (LPS)-induced fever and to elucidate their mechanisms of action.