The carotid body (CB) has been described as a metabolic sensor implicated in the genesis of insulin resistance and glucose intolerance (1-2). Hence, modulation of the activity of its sensitive nerve, the carotid sinus nerve (CSN) could be a therapeutic strategy for metabolic diseases (MD) (3). Knowing that non-alcoholic fatty liver disease is regarded as the hepatic manifestation of MD and since the liver has a fundamental role in dysmetabolism (4), herein we investigated the effect of CSN resection on liver function in young and aged animals with metabolic dysfunction exacerbated by long-term hypercaloric diet consumption. Male Wistar rats (8-10 weeks) were used: a control (CTL) group fed a standard diet and a high-fat high-sucrose (HFHSu) group fed with a 60% lipid-rich diet-35% sucrose, during 14 and 44 weeks. After this period, animals were anesthetized (medetomidine 0.5 mg/kg; ketamine 75 mg/kg) and submitted to CSN resection or to a sham surgery, with 9 weeks follow-up. At a terminal experiment, the liver was collected for hematoxylin/eosin (H&E) and Massons trichrome staining. Liver triglycerides (TGL) and lipid content were measured, as western blots of key proteins involved in tissue inflammation and fibrosis. Serum total cholesterol and TGL were evaluated. One- and two-way Anova tests were used. Laboratory care was in accordance with the European Union Directive for Protection of Vertebrates Used for experimental and Other Scientific Ends (2010/63/EU). Ageing and long-term HFHSu diet consumption increased total cholesterol levels (CTL Young= 82.22±4.25mg/dl; CTL Old=97.74±25.77mg/dl; HFHSu Old=111.30±13.12mg/dl, p<0.01) as well as serum TGL (CTL Young=83.18±13.72mg/dl; CTL Old=142.65±32.35mg/dl; HFHSu Young= 134.40 ±32.35mg/dl, p<0.05; HFHSu Old=118.87±38.66mg/dl), an effect that was restored with the CSN resection in HFHSu animals. Liver TGL levels increased with age and diet (CTL Young= 8.15±0.83µmoles/mg liver; CTL Old=13.48±2.45µmoles/mg liver; HFHSu Young=10.58±1.73µmoles/mg liver; HFHSu Old=42.34±3.01µmoles/mg liver, p<0.0001), an effect that decreased with CSN resection (HFHSu Old with CSN resection=17.55±1.09 µmoles/mg liver, p<0.001). Ageing increased liver lipid deposition (CTL Young=1.48±0.10gr-1 liver; CTL Old=2.98±0.25gr-1 liver) an effect that was exacerbated by HFHSu diet (HFHSu Young=2.19±0.30gr-1 liver, p<0.01; HFHSu Old=5.47±0.56gr-1 liver, p<0.0001). CSN resection decreased liver lipid deposition by 21.46 (p<0.01) and 35.28% (p<0.001) in young and old HFHSu animals, respectively, results that were supported by H&E staining. In conclusion, ageing induced an increase in the levels of total cholesterol, TGL and lipid deposition in the liver, an effect that was exacerbated by long-term hypercaloric diet consumption. Moreover, CSN resection ameliorated these effects. Our results suggest that modulation of CB activity might be important in liver-associated metabolic dysfunctions in young and old animals.