Evaluation of alternate day fasting modulating effect on cGAS-STING Pathway and Syntaxin17 as markers of the cross-talk between macrophages and adipocytes in rats with induced obesity

Background: Obesity is a worldwide pandemic with profound health consequences for individuals and societies. Chronic low-grade inflammation and disrupted immune signaling within adipose tissue are central mechanisms driving these complications. Communication between macrophages and adipocytes has become recognized as a key factor governing inflammatory responses and metabolic balance in obesity. The stimulator of interferon genes (STING) and syntaxin-17 (STX17) have gained attention as critical regulators of immune activation and cellular stress responses. Alternate-day fasting (ADF) is a promising dietary intervention with reported anti-inflammatory benefits. The aim of this work was to evaluate the modulatory effect of alternate day fasting (ADF) on stimulator of interferon genes (STING) expression and syntaxin17 (STX17) levels in adipose tissue as markers of the crosstalk between macrophages and adipocytes in rats with high-fructose diet induced obesity. Methods: Our study was conducted on Forty-eight male albino rats that were divided into four equal groups: control group, fasting-control group, HFD group and fasting-HFD group. Samples of adipose tissue were dissected for histopathological examination. Adipose tissue levels of STX17 and inducible nitric oxide synthase (iNOS) were measured by ELISA. Levels of nitric oxide (NO) were measured by spectrophotometer. STING expression levels were evaluated by qRT PCR. Results: Our study showed that ADF has significantly downregulated STING mRNA expression levels and decreased levels of STX17, iNOS, NO in adipose tissue homogenate in fasting-HFD group compared to HFD group. Conclusion: These findings highlight the role of ADF as a dietary intervention on inflammation amelioration along with immune and autophagy regulation, which were mediated through enhanced adipocyte-macrophage crosstalk.