High-fat diet-induced inflammatory response in ventral tegmental area of midbrain triggers food reward dysfunction in obesity-prone rats
10.3969/j.issn.1000-4718.2025.11.002
- VernacularTitle:高脂膳食诱导肥胖易感大鼠中脑腹侧被盖区炎症反应引发食物奖赏异常
- Author:
Yuxi DAI
1
;
Weihuan WANG
1
;
Wei CHEN
1
;
Yuxiu HE
1
Author Information
1. 河北师范大学体育学院,河北省人体运动生物信息测评重点实验室,河北 石家庄 050024
- Publication Type:Journal Article
- Keywords:
obesity;
food reward;
metaflammation;
ventral tegmental area
- From:
Chinese Journal of Pathophysiology
2025;41(11):2091-2099
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to investigate distinct patterns in food reward behavior and neuroinflammato-ry responses within the ventral tegmental area(VTA)between obesity-prone(OP)and obesity-resistant(OR)rats,while elucidating their potential interplay.METHODS:Twenty-four male Sprague-Dawley rats(5-week-old)were adminis-tered a high-fat diet(HFD)for 8 weeks.Based on body weight tertiles,rats were stratified into OP(highest tertile,n=8)and OR(lowest tertile,n=8)groups.Food reward function was evaluated through conditioned place preference(CPP)test and operant food-seeking task(OFST).Serum lipid profiles were quantified via colorimetric microplate assays,with 24-hour energy expenditure monitored using CLAMS.Western blot and immunofluorescence assays quantified ionized cal-cium-binding adaptor molecule 1(Iba1)and tyrosine hydroxylase(TH)protein expression,while immunofluorescence lo-calized VTA-positive cell spatial distribution and density.RT-qPCR quantified mRNA expression of Iba1,TH,and proin-flammatory cytokines(TNF-α,IL-1β and IL-6).ELISA quantified proinflammatory cytokine protein concentrations.RE-SULTS:Following 8-week HFD exposure,OP rats exhibited elevated body weight,total food and calories,adiposity,Lee index,and levels of TG,LDL-C,TC,and NEFA,while HLD-C levels and 24-hour energy metabolism significantly decreased(P<0.05).OP rats demonstrated enhanced CPP preference for HFD-paired cues,elevated lever pressing fre-quency,and increased breakpoints versus OR counterparts(P<0.05),positively correlating with body weight(r=0.766,0.561 and 0.606;P<0.05).OP rats demonstrated elevated Iba1 positive cell density,protein and mRNA expression,and inflammatory mediators in VTA versus OR counterparts,contrasting with diminished TH positive neurons showing re-duced protein and mRNA levels(P<0.05).VTA neuroinflammatory mediators(Iba1,TNF-α,IL-1β and IL-6)exhibited inverse correlations with TH protein expression(r=-0.953,-0.866,-0.881 and-0.886;P<0.05).CONCLUSION:The OP rats exhibit attenuated reward sensitivity,elevated HFD preference,and increased palatable food-seeking behavior.These behavioral modifications correlate with VTA neuroinflammation suppressing dopaminergic(DA)biosynthesis.
