Effects Of Supplemental Tart Cherry and Fish Oil on Inflammation and Gut Microbiota Composition in Diet-Induced (C57BL/6J) and Genetically (TALLYHO/Jng) Obese Mice

Obesity is a chronic and complex metabolic disease that increases the risk of other comorbidities such as type 2 diabetes, cardiovascular diseases, and cancer. As obesity develops, white adipose tissue (WAT) undergoes remodeling, accompanied by chronic low-grade inflammation and disruptions in key homeostatic process, including inflammatory signaling, metabolism, endoplasmic reticulum (ER) stress, and autophagy. Additionally, obesity is associated with gut microbiota dysbiosis and compromised intestinal barrier integrity, further exacerbating inflammation and metabolic dysfunctions. While bioactive compounds such as fish oil (FO) and tart cherry (TC) have documented anti-inflammatory properties, their potential additive or synergistic effects remain unclear. This dissertation investigates the individual and combined effects of FO and TC on inflammation, WAT function, gut microbiota composition, and gut integrity in both diet-induced (C57BL/6J, B6) and genetically (TALLYHO/Jng, TH) obese mouse models, with a particular focus on sex and genotype-specific metabolic responses. We analyzed the expressions of key markers in gonadal WAT, liver, and colon, along with gut microbiota composition using 16S rRNA sequencing in cecal samples. These analyses were conducted using samples from a previous study in which male and female B6 and TH mice were fed low-fat (LF), high fat (HF), or HF diets supplemented with tart cherry (TC), fish oil (FO), or their combination (TC+FO) for 14 weeks from weaning. Our lab previously reported that HF diet significantly increased adiposity but only FO improved glucose clearance in TH mice [1]. In our current study, we demonstrated that HF diet upregulated markers of inflammation, ER stress, and autophagy in WAT across both male and female B6 and TH mice [2]. Additionally, Supplementation with either TC or FO attenuated above stress responses, while their combination did not consistently enhance these effects beyond individual supplementation[2]. Moreover, HF diet significantly disrupted gut microbial homeostasis, characterized by a reduction in some beneficial bacterial taxa and a concomitant increase in potentially pathogenic ones. This dysbiosis was associated with compromised gut barrier function, evidenced by decreased expression of tight junction proteins and mucin genes, with more pronounced effects observed in female mice. Notably, both TC and FO supplementation individually improved gut microbiota composition and enhanced intestinal barrier integrity through upregulation of tight junction and mucin gene expression compared to HF diet. However, the combined supplementation of TC and FO did not consistently produce synergistic or additive benefits beyond those observed with individual treatments. Our study provides novel insights into the individual and combined effects of TC and FO on inflammation, gut microbiota composition, and gut barrier integrity in diet-induced and genetic obese mice. Although further studies are needed to explore different dose combinations before concluding potential additive or synergistic effects of FO and TC, our data demonstrate the sex and genotype specific responses. Overall, these findings highlight the complex interplay between diet, genetic, and sex in shaping metabolic and gut health responses to dietary bioactives. This underscores the importance of personalized nutrition strategies that consider genetic and sex-specific factors in the development of targeted interventions for obesity management. Further research is warranted to investigate the role of the microbiome and other mechanisms mediating the metabolic effects of these bioactive compounds.