Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice

Abstract

Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction.

Vicarious Social Defeat Increases Conditioned Rewarding Effects of Cocaine and Ethanol Intake in Female Mice

“…Since caloric intake and satiety are some components of feeding behavior that are also important modulators of oral alcohol SA, we have to point out that the protocol of alcohol SA employed in this study did not require food deprivation. We have previously validated this oral SA procedure in male mice [65]. In the present study, we have confirmed that this SA proved to be sensitive to detecting long-lasting social stress effects.…”

Differential proteomic analysis of mouse cerebrums with high-fat diet (HFD)-induced hyperlipidemia

“…Cx3cl1 is a well-known proinflammatory chemokine and has been reported to be altered by HFD despite of some conflicts in the published results. For example, increased level of Cx3cl1 was reported after HFD consumption and induced neuroinflammation-relevant process ( Morari et al, 2014 ; Gonzalez-Portilla et al, 2021 ), while decreased Cx3cl1 expression in hippocampus and amygdala was reported in HFD-induced obese mice that showed significant cognitive deficits ( Kawamura et al, 2021 ). Unveiling of the causes that led to the dysregulation of the protein in our study would need further studies.…”

Acute and Chronic Ethanol Effects during Adolescence on Neuroimmune Responses: Consequences and Potential Pharmacologic Interventions

“…injections and free access 10% ethanol) have shown an increase in IL-1β, TNF-α, and IL-6 in the hippocampus [20,27]. Additionally, studies have observed an increase in IL-6 and C-X3-X Motif Ligand 1 (CX3CL1) in the striatum in adulthood after 3 weeks of ethanol abstinence [28]. Interestingly, cytokines levels after ethanol exposure were exacerbated by a high-fat diet [28].…”

“…Additionally, studies have observed an increase in IL-6 and C-X3-X Motif Ligand 1 (CX3CL1) in the striatum in adulthood after 3 weeks of ethanol abstinence [28]. Interestingly, cytokines levels after ethanol exposure were exacerbated by a high-fat diet [28]. Additionally, it has been reported that ethanol-induced cytokine expression can vary between sexes [29].…”